Publications by authors named "Cong Tan"

111 Publications

ITGB1 as a prognostic biomarker correlated with immune suppression in gastric cancer.

Cancer Med 2022 Jul 21. Epub 2022 Jul 21.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Introduction: Gastric cancer is one of the common malignant tumors with a high incidence and mortality in China. Prognostic biomarkers and potential predictors of the treatment efficacy of gastric cancer urgently need to be identified. Integrin-β (ITGB) is a superfamily of integrins and is involved in cell adhesion, tissue repair, immune response, and tumor metastasis.

Methods: We analyzed ITGB1 expression in our hospital samples of the gastric cancer cohort. And the public data of The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD), The Asian Cancer Research Group (ACRG)/GSE62254, and GSE15459 data sets were analyzed by using the bioinformatic methods. The relationships between ITGB1 expression and clinicopathological features, patient prognosis, activation of the Wnt/β-catenin signaling pathway, and tumor immunosuppressive factors were also explored.

Results: The positive rate of ITGB1 expression in the Fudan University Shanghai Cancer Center gastric cancer tumor tissues was 61.4% (258/420) and correlated with deep invasion (p = 0.017), an advanced clinical stage (p = 0.011), and a poor prognosis (p < 0.05). The TCGA-STAD/ACRG/GSE15459 cohorts also showed similar results. ITGB1 is one of the upstream molecules of the Wnt/β-catenin signaling pathway and is correlated with tumor immune suppression. In gastric cancer, we found a correlation between ITGB1 expression and Wnt/β-catenin signaling pathway activity. In the TCGA-STAD/ACRG/GSE15459 cohorts, ITGB1 expression was positively associated with immunosuppressive factors and negatively associated with immunoactive factors. Patients with low ITGB1 expression exhibited a significantly high immunotherapy response ratio according to an analysis of tumor immune dysfunction and exclusion (TIDE), which may indicate that ITGB1 is a potential predictor of immunotherapy efficacy.

Conclusions: ITGB1 affects the prognosis in gastric cancer patients and plays a core role in immune suppression in gastric cancer.
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http://dx.doi.org/10.1002/cam4.5042DOI Listing
July 2022

Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer.

J Gastrointest Oncol 2022 Jun;13(3):1035-1045

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Alpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC.

Methods: We retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC.

Results: Our results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without.

Conclusions: This study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient's preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.
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http://dx.doi.org/10.21037/jgo-22-462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274048PMC
June 2022

Identification of ABCA5 among ATP-Binding Cassette Transporter Family as a New Biomarker for Colorectal Cancer.

J Oncol 2022 22;2022:3399311. Epub 2022 Jun 22.

Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, China.

Background: The increasing incidence and mortality of colorectal cancer (CRC) urgently requires updated biomarkers. The ABC transporter family is a widespread family of membrane-bound proteins involved in the transportation of substrates associated with ATP hydrolysis, including metabolites, amino acids, peptides and proteins, sterols and lipids, organic and inorganic ions, sugars, metals, and drugs. They play an important role in the maintenance of homeostasis in the body.

Purpose: This study aims to search for new markers in the ABC transporter gene family for diagnostic and prognostic purposes through data mining of The Cancer Genome Atlas (TCGA) and GEO (Gene Expression Omnibus) datasets.

Methods: A total of 980 samples, including 684 CRC patients and 296 controls from five different datasets, were included for analysis. The construction of the PPI (protein-protein interaction) network and pathway analysis were performed in STRING database and DAVID (database for annotation, visualization, and integrated discovery), respectively. In addition, GSEA (gene set enrichment analysis) and WGCNA (weighted gene co-expression network analysis) were also used for functional analysis.

Results: After several rounds of screening and validation, only the gene was retained among the 49 genes.

Conclusions: The results demonstrated that expression is reduced in CRC and patients with high expression have better OS, which can provide guidance for better management and treatment of CRC in the future.
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http://dx.doi.org/10.1155/2022/3399311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242773PMC
June 2022

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BMC Cancer 2022 Jun 28;22(1):710. Epub 2022 Jun 28.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, People's Republic of China.

Background: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC.

Methods: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy.

Discussion: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety.

Trial Registration: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-022-09786-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238164PMC
June 2022

Calcipotriol abrogates cancer-associated fibroblast-derived IL-8-mediated oxaliplatin resistance in gastric cancer cells via blocking PI3K/Akt signaling.

Acta Pharmacol Sin 2022 Jun 8. Epub 2022 Jun 8.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Activation of vitamin D receptor (VDR) in cancer-associated fibroblasts (CAFs) has been implicated in hesitating tumor progression and chemoresistance of several human malignancies. Yet, the role of VDR in CAF-induced chemotherapy resistance of gastric cancer (GC) cells remains elusive. In this study we first conducted immunohistochemistry analysis on tissue microarrays including 88 pairs of GC and normal mucosa samples, and provided clinical evidence that VDR was mainly expressed in gastric mucous cells but almost invisible in CAFs, and VDR expression was negatively correlated with malignant clinical phenotype and advanced stages, low VDR expression confers to poor overall survival rate of patients with GC. In a co-culture system of primary CAFs and cancer cells, we showed that treatment of HGC-27 and AGS GC cells with VDR ligand calcipotriol (Cal, 500 nM) significantly inhibited CAF-induced oxaliplatin resistance. By using RNA-sequencing and Human Cytokine Antibody Array, we demonstrated that IL-8 secretion from CAFs induced oxaliplatin resistance via activating the PI3K/AKT pathway in GC, whereas Cal treatment greatly attenuated the tumor-supportive effect of CAF-derived IL-8 on GC cells. Taken together, this study verifies the specific localization of VDR in GC tissues and demonstrates that activation of VDR abrogates CAF-derived IL-8-mediated oxaliplatin resistance in GC via blocking PI3K/Akt signaling, suggesting vitamin D supplementation as a potential strategy of enhancing the anti-tumor effect of chemotherapy in GC.
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http://dx.doi.org/10.1038/s41401-022-00927-1DOI Listing
June 2022

NAD-capped RNAs are widespread in rice (Oryza sativa) and spatiotemporally modulated during development.

Sci China Life Sci 2022 May 26. Epub 2022 May 26.

Guangdong Provincial Key Laboratory for Plant Epigenetics, Longhua Bioindustry and Innovation Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, China.

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http://dx.doi.org/10.1007/s11427-021-2113-7DOI Listing
May 2022

Human Epidermal Growth Factor Receptor 2 Overexpression and Amplification in Patients With Colorectal Cancer: A Large-Scale Retrospective Study in Chinese Population.

Front Oncol 2022 28;12:842787. Epub 2022 Apr 28.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Cumulative evidence in colorectal cancer (CRC) suggests that patients with human epidermal growth factor receptor 2 (HER2) overexpression or amplification can benefit from anti-HER2 therapy. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to currently utilized HER2 diagnostic criteria in a large cohort of Chinese CRC patients.

Methods: HER2 protein expression was tested by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) samples from 4,836 CRC patients in our institution. Breast cancer (BC) and gastroesophageal adenocarcinoma (GEA) criteria, as well as the HERACLES criteria, were used for the determination of HER2 status. Dual-color silver-enhanced hybridization (DSISH) was performed in all IHC 2+~3+ cases determined by BC/GEA criteria.

Results: The HER2 expression rate of IHC (1+~3+) was 7.01% (339/4,836) and 6.02% (291/4,836) in CRCs based on the BC/GEA criteria and the HERACLES criteria, respectively, while combined DSISH results in the HER2 amplification/overexpression ratio of 3.39% (164/4,836) in our cohort. HER2 expression detected by IHC was positively correlated with the female gender, whereas the HER2 overexpression/amplification showed no correlation with any clinicopathological parameter. In addition, no significant correlation was found between HER2 statuses and either disease-free survival or overall survival regardless of the evaluation criterion used. However, patients with HER2 1+ CRC showed a tendency of having the shortest overall survival as compared with any other group of patients according to the HERACLES criteria, and this trend has always existed in the rectal location, T3 stage, and TNM stage II, medium differentiation, and perineural invasion stratified group. Furthermore, the HER2 protein expression was significantly negatively correlated with RAS/BRAF mutations according to the HERACLES criteria.

Conclusion: To our knowledge, this is the largest study of HER2 status in Asian patients with CRC. Our findings suggest that the current most commonly used HERACLES criteria might be too strict for patients with CRC. Future studies are needed to explore the most suitable criteria for screening CRC patients who could benefit from anti-HER2 therapy as much as possible.
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http://dx.doi.org/10.3389/fonc.2022.842787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097912PMC
April 2022

Molecular signatures of tumor progression in pancreatic adenocarcinoma identified by energy metabolism characteristics.

BMC Cancer 2022 Apr 13;22(1):404. Epub 2022 Apr 13.

Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, People's Republic of China.

Background: In this study, we performed a molecular evaluation of primary pancreatic adenocarcinoma (PAAD) based on the comprehensive analysis of energy metabolism-related gene (EMRG) expression profiles.

Methods: Molecular subtypes were identified by nonnegative matrix clustering of 565 EMRGs. An overall survival (OS) predictive gene signature was developed and internally and externally validated based on three online PAAD datasets. Hub genes were identified in molecular subtypes by weighted gene correlation network analysis (WGCNA) coexpression algorithm analysis and considered as prognostic genes. LASSO cox regression was conducted to establish a robust prognostic gene model, a four-gene signature, which performed better in survival prediction than four previously reported models. In addition, a novel nomogram constructed by combining clinical features and the 4-gene signature showed high-confidence clinical utility. According to gene set enrichment analysis (GSEA), gene sets related to the high-risk group participate in the neuroactive ligand receptor interaction pathway.

Conclusions: In summary, EMRG-based molecular subtypes and prognostic gene models may provide a novel research direction for patient stratification and trials of targeted therapies.
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http://dx.doi.org/10.1186/s12885-022-09487-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006543PMC
April 2022

Comprehensive molecular characterization and identification of prognostic signature in stomach adenocarcinoma on the basis of energy-metabolism-related genes.

World J Gastrointest Oncol 2022 Feb;14(2):478-497

Department of Medical Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Background: Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, but its molecular and prognostic characteristics has never been fully illustrated.

Aim: To describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures.

Methods: We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene (EMRG) expression profiles.

Results: On the basis of 86 EMRGs that were significantly associated to patients' progression-free survival (PFS), we propose a molecular classification dividing gastric cancer into two subtypes: Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process. Compared with patients with low-risk score, patients with high-risk score had shorter overall survival. Furthermore, calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures. According to gene set enrichment analysis, gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway.

Conclusion: Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.
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http://dx.doi.org/10.4251/wjgo.v14.i2.478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919002PMC
February 2022

Multi-center evaluation of artificial intelligent imaging and clinical models for predicting neoadjuvant chemotherapy response in breast cancer.

Breast Cancer Res Treat 2022 May 9;193(1):121-138. Epub 2022 Mar 9.

Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore.

Background: Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumors, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumors' response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC.

Methods: The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on deep learning (DL). Clinical parameters were included to build a final prognostic model.

Results: The best performing models were based on space-resolved and DL approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855).

Conclusions: Radiomics features extracted from diagnostic CT augment the predictive ability of pCR when combined with clinical features. The novel space-resolved radiomics and DL radiomics approaches outperformed conventional radiomics techniques.
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http://dx.doi.org/10.1007/s10549-022-06521-7DOI Listing
May 2022

The Value of Whole-Tumor Histogram and Texture Analysis Using Intravoxel Incoherent Motion in Differentiating Pathologic Subtypes of Locally Advanced Gastric Cancer.

Front Oncol 2022 9;12:821586. Epub 2022 Feb 9.

Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: To determine if whole-tumor histogram and texture analyses using intravoxel incoherent motion (IVIM) parameters values could differentiate the pathologic characteristics of locally advanced gastric cancer.

Methods: Eighty patients with histologically confirmed locally advanced gastric cancer who received surgery in our institution were retrospectively enrolled into our study between April 2017 and December 2018. Patients were excluded if they had lesions with the smallest diameter < 5 mm and severe image artifacts. MR scanning included IVIM sequences (9 b values, 0, 20, 40, 60, 100, 150,200, 500, and 800 s/mm) used in all patients before treatment. Whole tumors were segmented by manually drawing the lesion contours on each slice of the diffusion-weighted imaging (DWI) images (with b=800). Histogram and texture metrics for IVIM parameters values and apparent diffusion coefficient (ADC) values were measured based on whole-tumor volume analyses. Then, all 24 extracted metrics were compared between well, moderately, and poorly differentiated tumors, and between different Lauren classifications, signet-ring cell carcinomas, and other poorly cohesive carcinomas using univariate analyses. Multivariate logistic analyses and multicollinear tests were used to identify independent influencing factors from the significant variables of the univariate analyses to distinguish tumor differentiation and Lauren classifications. ROC curve analyses were performed to evaluate the diagnostic performance of these independent influencing factors for determining tumor differentiation and Lauren classifications and identifying signet-ring cell carcinomas. The interobserver agreement was also conducted between the two observers for image quality evaluations and parameter metric measurements.

Results: For diagnosing tumor differentiation, the ADC, pure diffusion coefficient median (Dslow), and pure diffusion coefficient entropy (Dslow) showed the greatest AUCs: 0.937, 0.948, and 0.850, respectively, and no differences were found between the three metrics, P>0.05). The 95th percentile perfusion factor (FP ) was the best metric to distinguish diffuse-type GCs vs. intestinal/mixed (AUC=0.896). The ROC curve to distinguish signet-ring cell carcinomas from other poorly cohesive carcinomas showed that the Dslow had AUC of 0.738. For interobserver reliability, image quality evaluations showed excellent agreement (interclass correlation coefficient [ICC]=0.85); metrics measurements of all parameters indicated good to excellent agreement (ICC=0.65-0.89), except for the Dfast metric, which showed moderate agreement (ICC=0.41-0.60).

Conclusions: The whole-tumor histogram and texture analyses of the IVIM parameters based on the biexponential model provided a non-invasive method to discriminate pathologic tumor subtypes preoperatively in patients with locally advanced gastric cancer. The metric FP derived from IVIM performed better in determining Lauren classifications than the mono-exponential model.
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http://dx.doi.org/10.3389/fonc.2022.821586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864172PMC
February 2022

Development of a novel combined nomogram model integrating deep learning-pathomics, radiomics and immunoscore to predict postoperative outcome of colorectal cancer lung metastasis patients.

J Hematol Oncol 2022 01 24;15(1):11. Epub 2022 Jan 24.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.

Limited previous studies focused on the death and progression risk stratification of colorectal cancer (CRC) lung metastasis patients. The aim of this study is to construct a nomogram model combing machine learning-pathomics, radiomics features, Immunoscore and clinical factors to predict the postoperative outcome of CRC patients with lung metastasis. In this study, a total of 103 CRC patients having metastases limited to lung and undergoing radical lung resection were identified. Patch-level convolutional neural network training in weakly supervised manner was used to perform whole slides histopathological images survival analysis. Synthetic minority oversampling technique and support vector machine classifier were used to identify radiomics features and build predictive signature. The Immunoscore for each patient was calculated from the density of CD3+ and CD8+ cells at the invasive margin and the center of metastatic tumor which were assessed on consecutive sections of automated digital pathology. Finally, pathomics and radiomics signatures were successfully developed to predict the overall survival (OS) and disease free survival (DFS) of patients. The predicted pathomics and radiomics scores are negatively correlated with Immunoscore and they are three independent prognostic factors for OS and DFS prediction. The combined nomogram showed outstanding performance in predicting OS (AUC = 0.860) and DFS (AUC = 0.875). The calibration curve and decision curve analysis demonstrated the considerable clinical usefulness of the combined nomogram. Taken together, the developed nomogram model consisting of machine learning-pathomics signature, radiomics signature, Immunoscore and clinical features could be reliable in predicting postoperative OS and DFS of colorectal lung metastasis patients.
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http://dx.doi.org/10.1186/s13045-022-01225-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785554PMC
January 2022

SWI/SNF Complex-deficient Undifferentiated Carcinoma of the Gastrointestinal Tract: Clinicopathologic Study of 30 Cases With an Emphasis on Variable Morphology, Immune Features, and the Prognostic Significance of Different SMARCA4 and SMARCA2 Subunit Deficiencies.

Am J Surg Pathol 2022 07 23;46(7):889-906. Epub 2021 Nov 23.

Department of Pathology, Fudan University Shanghai Cancer Center.

Undifferentiated carcinoma of the gastrointestinal tract has variable rhabdoid features. Expression of switch/sucrose nonfermenting (SWI/SNF) complex subunits is reportedly lost in a portion of cases; however, the prognostic significance of this loss remains unknown. Herein, 30 undifferentiated carcinoma cases were assessed for the expression of 4 SWI/SNF complex subunits (SMARCB1, SMARCA2, SMARCA4, and ARID1A). Tumor origin sites comprised stomach (40.0%), large intestine (20.0%), small intestine (16.7%), lower esophagus and stomach fundus (13.3%), ileocecal junction (3.3%), rectum (3.3%), and pancreas (3.3%). The tumors were composed of epithelioid neoplastic cells arranged in diffuse solid or discohesive sheets, nests, cords, poor cohesive pseudoglandular, and trabecular patterns. Rhabdoid tumor cells were identified in 66.7% (20/30) of cases. In total, 29/30 (96.7%) showed complete loss of at least 1 SWI/SNF subunit: SMARCA4-/SMARCA2- (11), isolated SMARCA4- (2), SMARCA4-/SMARCA2 unknown (6), isolated SMARCA2- (7), SMARCA2-/ARID1A- (1), and isolated ARID1A- (2). Negative or decreased expression (≤10% positive) of pan-cytokeratin was observed in 58.6% (17/29) of cases. In addition, 66.7% (20/30) of patients were late-stage (III or IV), and 65.2% (15/23) of stage IIB to IV patients succumbed to the disease at a mean clinical follow-up of 12.7 months. Specifically, patients with loss of SMARCA4 expression had the worst overall survival (P=0.028) and disease-free survival (P=0.006) rates, compared with those with SMARCA4 expression. The loss or decreased expression of epithelial markers is thus common in SWI/SNF complex-deficient undifferentiated carcinoma of the gastrointestinal tract, and loss of SMARCA4 correlates with poor prognosis.
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http://dx.doi.org/10.1097/PAS.0000000000001836DOI Listing
July 2022

VThunter: a database for single-cell screening of virus target cells in the animal kingdom.

Nucleic Acids Res 2022 01;50(D1):D934-D942

BGI-Shenzhen, Shenzhen 518083, China.

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.
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http://dx.doi.org/10.1093/nar/gkab894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728219PMC
January 2022

RNA-binding protein IMP3 is a novel regulator of MEK1/ERK signaling pathway in the progression of colorectal Cancer through the stabilization of MEKK1 mRNA.

J Exp Clin Cancer Res 2021 Jun 21;40(1):200. Epub 2021 Jun 21.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Background: MEK1/ERK signaling pathway plays an important role in most tumor progression, including colorectal cancer (CRC), however, MEK1-targeting therapy has little effective in treating CRC patients, indicating there may be a complex mechanism to activate MEK1/ERK signaling pathway except RAS activated mechanism.

Methods: To investigate the clinical significance of IMP3, we analyzed its expression levels in publicly available dataset and samples from Fudan University Shanghai Cancer Center. The effects of IMP3 on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. To investigate the role of IMP3 in colon carcinogenesis, conditional IMP3 knockout C57BL/6 mice was generated. The IMP3/MEKK1/MEK/ERK signaling axis in CRC was screened and validated by RNA-sequencing, RNA immunoprecipitation, luciferase reporter and western blot assays.

Results: We find RNA binding protein IMP3 directly bind to MEKK1 mRNA 3'-UTR, which regulates its stability, promote MEKK1 expression and sequentially activates MEK1/ERK signaling. Functionally, IMP3 promote the malignant biological process of CRC cells via MEKK1/MEK1/ERK signaling pathway both in vitro and in vivo, Moreover, IMP3 mice show decreased the expression of MEKK1 as well as colorectal tumors compared with wild-type mice after treatment with azoxymethane/dextran sodium sulfate. Clinically, the expression of IMP3 and MEKK1 are positive correlated, and concomitant IMP3 and MEKK1 protein levels negatively correlate with metastasis in CRC patients. In addition, MEK1 inhibitor in combination with shRNA-IMP3 have a synergistic effect both in vitro and in vivo.

Conclusion: Our study demonstrates that IMP3 regulates MEKK1 in CRC, thus activating the MEK1/ERK signaling in the progression of colorectal cancer, Furthermore, these results provide new insights into potential applications for combining MEK1 inhibitors with other target therapy such as IMP3 in preclinical trials for CRC patients.
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http://dx.doi.org/10.1186/s13046-021-01994-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215736PMC
June 2021

Genomic structural equation modelling provides a whole-system approach for the future crop breeding.

Theor Appl Genet 2021 Sep 31;134(9):2875-2889. Epub 2021 May 31.

Western Crop Genetics Alliance, Agricultural Sciences, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia.

Key Message: Using genomic structural equation modelling, this research demonstrates an efficient way to identify genetically correlating traits and provides an effective proxy for multi-trait selection to consider the joint genetic architecture of multiple interacting traits in crop breeding. Breeding crop cultivars with optimal value across multiple traits has been a challenge, as traits may negatively correlate due to pleiotropy or genetic linkage. For example, grain yield and grain protein content correlate negatively with each other in cereal crops. Future crop breeding needs to be based on practical yet accurate evaluation and effective selection of beneficial trait to retain genes with the best agronomic score for multiple traits. Here, we test the framework of whole-system-based approach using structural equation modelling (SEM) to investigate how one trait affects others to guide the optimal selection of a combination of agronomically important traits. Using ten traits and genome-wide SNP profiles from a worldwide barley panel and SEM analysis, we revealed a network of interacting traits, in which tiller number contributes positively to both grain yield and protein content; we further identified common genetic factors affecting multiple traits in the network of interaction. Our method demonstrates an efficient way to identify genetically correlating traits and underlying pleiotropic genetic factors and provides an effective proxy for multi-trait selection within a whole-system framework that considers the joint genetic architecture of multiple interacting traits in crop breeding. Our findings suggest the promise of a whole-system approach to overcome challenges such as the negative correlation of grain yield and protein content to facilitating quantitative and objective breeding decisions in future crop breeding.
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http://dx.doi.org/10.1007/s00122-021-03865-4DOI Listing
September 2021

Rapid progression of an IDH-wild type histological low-grade glioma harbouring TERT promoter mutation and diffuse CD34 expression: a case report.

Folia Neuropathol 2021 ;59(1):104-111

Department of Pathology, Shanghai Changzheng Hospital, Shanghai, China.

IDH-wild type (WT) histological low-grade gliomas are a rare group with distinct character and prognostic heterogeneity. Studies involving genetic and molecular analyses are warranted to stratify these patients into specific entities for the facilitation of tumour management. In this study, we reported a novel IDH-WT glioma with histological characteristics of a low-grade tumour. Preoperative CT revealed massive calcification of this lesion and MRI showed a mixed hyperintense and hypointense signals on both T1- and T2-weighted images with a slight contrast enhancement. Micrography revealed dense deposits of calcium and diffuse microhaemorrhage in the tumour mass. Immunohistochemical staining showed diffuse expression of CD34 in neoplastic cells but uncertain positivity of glial fibrillary acidic protein (GFAP). Further sequencing found telomerase reverse transcriptase (TERT) promoter mutation in this tumour. Though the patient underwent surgical treatment followed by radiotherapy and temozolomide chemotherapy, the tumour recurred at the eight-month follow-up postoperatively. Taken together, extensive CD34 expression and TERT promoter mutation may empower the potential of malignant transformation to IDH-WT histological low-grade glioma to rapidly progress into glioblastoma.
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http://dx.doi.org/10.5114/fn.2021.104471DOI Listing
November 2021

Stanniocalcin-2 promotes cell EMT and glycolysis via activating ITGB2/FAK/SOX6 signaling pathway in nasopharyngeal carcinoma.

Cell Biol Toxicol 2022 04 2;38(2):259-272. Epub 2021 Apr 2.

Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.
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http://dx.doi.org/10.1007/s10565-021-09600-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986754PMC
April 2022

Stromal Organization as a Predictive Biomarker of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

J Gastrointest Surg 2021 08 5;25(8):2116-2118. Epub 2021 Feb 5.

Department of Colorectal Surgery, Changzheng Hospital, Shanghai, People's Republic of China.

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http://dx.doi.org/10.1007/s11605-021-04920-7DOI Listing
August 2021

A global barley panel revealing genomic signatures of breeding in modern Australian cultivars.

Plant J 2021 04 9;106(2):419-434. Epub 2021 Mar 9.

Western Crop Genetics Alliance, Agricultural Sciences, College of Science, Health, Engineering and Education, Murdoch University, 90 South Street, Murdoch, WA, 6150, Australia.

The future of plant cultivar improvement lies in the evaluation of genetic resources from currently available germplasm. Today's gene pool of crop genetic diversity has been shaped during domestication and more recently by breeding. Recent efforts in plant breeding have been aimed at developing new and improved varieties from poorly adapted crops to suit local environments. However, the impact of these breeding efforts is poorly understood. Here, we assess the contributions of both historical and recent breeding efforts to local adaptation and crop improvement in a global barley panel by analysing the distribution of genetic variants with respect to geographic region or historical breeding category. By tracing the impact that breeding had on the genetic diversity of Hordeum vulgare (barley) released in Australia, where the history of barley production is relatively young, we identify 69 candidate regions within 922 genes that were under selection pressure. We also show that modern Australian barley varieties exhibit 12% higher genetic diversity than historical cultivars. Finally, field-trialling and phenotyping for agriculturally relevant traits across a diverse range of Australian environments suggests that genomic regions under strong breeding selection and their candidate genes are closely associated with key agronomic traits. In conclusion, our combined data set and germplasm collection provide a rich source of genetic diversity that can be applied to understanding and improving environmental adaptation and enhanced yields.
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http://dx.doi.org/10.1111/tpj.15173DOI Listing
April 2021

BarleyVarDB: a database of barley genomic variation.

Database (Oxford) 2020 11;2020

Western Barley Genetics Alliance, Agricultural Sciences, College of Science, Health, Engineering and Education, Murdoch University, 90 South Street, Murdoch, WA 6150, Australia.

Barley (Hordeum vulgare L.) is one of the first domesticated grain crops and represents the fourth most important cereal source for human and animal consumption. BarleyVarDB is a database of barley genomic variation. It can be publicly accessible through the website at http://146.118.64.11/BarleyVar. This database mainly provides three sets of information. First, there are 57 754 224 single nuclear polymorphisms (SNPs) and 3 600 663 insertions or deletions (InDels) included in BarleyVarDB, which were identified from high-coverage whole genome sequencing of 21 barley germplasm, including 8 wild barley accessions from 3 barley evolutionary original centers and 13 barley landraces from different continents. Second, it uses the latest barley genome reference and its annotation information publicly accessible, which has been achieved by the International Barley Genome Sequencing Consortium (IBSC). Third, 522 212 whole genome-wide microsatellites/simple sequence repeats (SSRs) were also included in this database, which were identified in the reference barley pseudo-molecular genome sequence. Additionally, several useful web-based applications are provided including JBrowse, BLAST and Primer3. Users can design PCR primers to asses polymorphic variants deposited in this database and use a user-friendly interface for accessing the barley reference genome. We envisage that the BarleyVarDB will benefit the barley genetic research community by providing access to all publicly available barley genomic variation information and barley reference genome as well as providing them with an ultra-high density of SNP and InDel markers for molecular breeding and identification of functional genes with important agronomic traits in barley. Database URL: http://146.118.64.11/BarleyVar.
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http://dx.doi.org/10.1093/database/baaa091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698660PMC
November 2020

The barley pan-genome reveals the hidden legacy of mutation breeding.

Nature 2020 12 25;588(7837):284-289. Epub 2020 Nov 25.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences (ICS-CAAS), Beijing, China.

Genetic diversity is key to crop improvement. Owing to pervasive genomic structural variation, a single reference genome assembly cannot capture the full complement of sequence diversity of a crop species (known as the 'pan-genome'). Multiple high-quality sequence assemblies are an indispensable component of a pan-genome infrastructure. Barley (Hordeum vulgare L.) is an important cereal crop with a long history of cultivation that is adapted to a wide range of agro-climatic conditions. Here we report the construction of chromosome-scale sequence assemblies for the genotypes of 20 varieties of barley-comprising landraces, cultivars and a wild barley-that were selected as representatives of global barley diversity. We catalogued genomic presence/absence variants and explored the use of structural variants for quantitative genetic analysis through whole-genome shotgun sequencing of 300 gene bank accessions. We discovered abundant large inversion polymorphisms and analysed in detail two inversions that are frequently found in current elite barley germplasm; one is probably the product of mutation breeding and the other is tightly linked to a locus that is involved in the expansion of geographical range. This first-generation barley pan-genome makes previously hidden genetic variation accessible to genetic studies and breeding.
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http://dx.doi.org/10.1038/s41586-020-2947-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759462PMC
December 2020

CNGBdb: China National GeneBank DataBase.

Yi Chuan 2020 Aug;42(8):799-809

China National GeneBank, Shenzhen 518120, China.

China National GeneBank DataBase (CNGBdb) is a data platform aiming to systematically archiving and sharing of multi-omics data in life science. As the service portal of Bio-informatics Data Center of the core structure, namely, "Three Banks and Two Platforms" of China National GeneBank (CNGB), CNGBdb has the advantages of rich sample resources, data resources, cooperation projects, powerful data computation and analysis capabilities. With the advent of high throughput sequencing technologies, research in life science has entered the big data era, which is in the need of closer international cooperation and data sharing. With the development of China's economy and the increase of investment in life science research, we need to establish a national public platform for data archiving and sharing in life science to promote the systematic management, application and industrial utilization. Currently, CNGBdb can provide genomic data archiving, information search engines, data management and data analysis services. The data schema of CNGBdb has covered projects, samples, experiments, runs, assemblies, variations and sequences. Until May 22, 2020, CNGBdb has archived 2176 research projects and more than 2221 TB sequencing data submitted by researchers globally. In the future, CNGBdb will continue to be dedicated to promoting data sharing in life science research and improving the service capability. CNGBdb website is: https://db.cngb.org/.
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http://dx.doi.org/10.16288/j.yczz.20-080DOI Listing
August 2020

Development and validation of a DNA repair gene signature for prognosis prediction in Colon Cancer.

J Cancer 2020 12;11(20):5918-5928. Epub 2020 Aug 12.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Aberrant expression of DNA repair genes (DRGs) can be related to tumor progression and clinical outcomes in colon cancer. Here, we aimed to establish a DRGs signature to identify the vital prognostic DRGs in colon cancer. Firstly, gene set enrichment analysis (GSEA) was performed to demonstrate the association between abnormal expression level of DRGs and tumorigenesis. Then, a total of 476 DRGs were obtained for detecting candidate biomarkers in randomly selected 295 cases from The Cancer Genome Atlas (TCGA) colon cancer cohort. Eleven genes were screened by LASSO Cox regression analyses to develop the prognostic model. Then, the prognostic model and the expression levels of the eleven genes were validated using the internal validation dataset (the rest 125 cases in TCGA cohort) and an external validation dataset (obtained from Gene Expression Omnibus dataset). Further analysis revealed the independent prognostic capacity of the prognostic model in relation to other clinical characteristics. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the prognostic model. Furthermore, we provided a nomogram for interpreting the clinical application of the 11-DRG signature. In conclusion, we propose a newly developed 11-DRG signature as a practical prognostic predictor for patients with colon cancer, which can facilitate the individualized counselling and treatment.
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http://dx.doi.org/10.7150/jca.46328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477412PMC
August 2020

GCNT4 is Associated with Prognosis and Suppress Cell Proliferation in Gastric Cancer.

Onco Targets Ther 2020 25;13:8601-8613. Epub 2020 Aug 25.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, People's Republic of China.

Background: GCNT4 is a member of the glucosaminyl (N-acetyl) transferases family that has been implicated in multiple human malignancies. However, the role of GCNT4 in gastric cancer (GC) is unknown. In this present study, we aimed to explore the role and clinicopathological correlation of GCNT4 in GC.

Materials And Methods: We first evaluated the dysregulation of GCNT4 in The Cancer Genome Atlas (TCGA) and then we performed RT-qPCR and immunohistochemistry to validate the results in a cohort of in-house patients. The clinicopathological correlation and function of GCNT4 in GC were also analysed.

Results: GCNT4 was found to be significantly downregulated in GC. In addition, GCNT4 expression correlated with tumour depth, nervous invasion and pathological tumor-node-metastasis (pTNM) stage. Moreover, lower GCNT4 levels conferred poor overall survival (OS) and disease-free survival (DFS) to GC patients. Multivariate Cox regression analysis revealed that GCNT4 protein expression is an independent prognostic factor for OS in patients with GC. Further functional experimental results revealed that overexpression of GCNT4 appears to halt GC cell proliferation and the cell cycle.

Conclusion: Altogether, these findings indicated that GCNT4 regulates the GC cell cycle and have important implications for the selection of therapeutic targets to prevent tumour proliferation.
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http://dx.doi.org/10.2147/OTT.S248997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457769PMC
August 2020

Heterogeneous programmed death-ligand 1 expression in gastric cancer: comparison of tissue microarrays and whole sections.

Cancer Cell Int 2020 24;20:186. Epub 2020 May 24.

Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032 China.

Background: Programmed death-ligand 1 (PD-L1) expression determines the eligibility for anti-PD-1 treatment in patients with advanced gastric cancer, but evidence indicates that PD-L1 staining is heterogeneous. Patients who are ineligible for radical surgery could be tested for PD-L1 expression with biopsy staining, but it is unclear if a small biopsy is representative of the PD-L1 status of the whole tumor. The aim of our study was to determine how many biopsy specimens are needed to accurately reflect the objective status of PD-L1 expression in whole sections.

Methods: We built tissue microarrays (TMAs) as substitutes for core biopsies, collecting 6 cores per case from 152 gastric cancer specimens. All of the slides and TMAs underwent PD-L1 immunohistochemical staining, and PD-L1 expression in at least 1% of tumor cells or immune cells was defined as positive.

Results: It was necessary to randomly select multiple cores from TMAs to reach a suitable agreement rate (> 90%) and Cohen's κ value (> 0.8) between TMAs and whole sections. We defined the PD-L1 staining status from the whole section as the standard. The evaluation of five randomly selected cores from TMAs agreed well with the evaluation of whole sections. The sensitivity, specificity and the area under the curve (AUC) of the receiver-operating characteristic (ROC) were 0.93, 0.92, and 0.922 (95% confidence interval (CI) 0.863-0.982), respectively.

Conclusions: We conclude that PD-L1 expression among TMA samples had different degrees of relevance to the corresponding surgical specimens, which indicates that at least five biopsies might be necessary to characterize patients taking anti-PD-1 treatment.
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http://dx.doi.org/10.1186/s12935-020-01273-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247123PMC
May 2020

Dominant complementary interaction between OsC1 and two tightly linked genes, Rb1 and Rb2, controls the purple leaf sheath in rice.

Theor Appl Genet 2020 Sep 26;133(9):2555-2566. Epub 2020 May 26.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Key Message: Two tightly linked genes for rice purple leaf sheath were identified via map-based cloning. Further analysis indicated that these two genes together with OsC1 co-regulating the purple leaf sheath. The purple color of the leaf sheath in rice is dependent on the accumulation of anthocyanins such as cyanidin 3-O-glucoside (C3G) and peonidin 3-O-glucoside (P3G). Although many genes related to leaf sheath color have been mapped, the genetic basis for leaf sheath color is not yet clear. Here, PSH1 (purple leaf sheath 1) was mapped to chromosome 1 using an F and a RIL population. Map-based cloning and transformation assays further divided PSH1 as two tightly linked bHLH genes, Rb1 and Rb2. Ectopic expression of these two genes resulted in substantial accumulation of C3G and P3G in the leaf blade, leaf sheath and pericarp. Single gene mutants displayed a faded purple leaf sheath or green leaf sheath in the top half of the leaf sheath, but double mutants displayed a green leaf sheath, indicating that both genes have dosage effects on anthocyanin synthesis. However, overexpression of Rb1 and Rb2 sharply decreased grain filling. A segregation ratio of green to purple was 15:1 observed in the F population from parents Minghui 63 and Xizang 2, which both had green leaf sheaths; these results demonstrate that dominant complementary interaction between OsC1 and Rb (Rb1 and Rb2) controls the purple leaf sheath. These findings systematically uncovered the genetic basis of leaf sheath color and provided alternative genes for breeding anthocyanin-rich rice.
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http://dx.doi.org/10.1007/s00122-020-03617-wDOI Listing
September 2020

Fine mapping QSc.VR4, an effective and stable scald resistance locus in barley (Hordeum vulgare L.), to a 0.38-Mb region enriched with LRR-RLK and GLP genes.

Theor Appl Genet 2020 Jul 13;133(7):2307-2321. Epub 2020 May 13.

Western Barley Genetics Alliance, Western Australian State Agricultural Biotechnology Centre, School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA, Australia.

Key Message: An effective and stable quantitative resistance locus, QSc.VR4, was fine mapped, characterized and physically anchored to the short arm of 4H, conferring adult plant resistance to the fungus Rhynchosporium commune in barley. Scald caused by Rhynchosporium commune is one of the most destructive barley diseases worldwide. Accumulation of adult plant resistance (APR) governed by multiple resistance alleles is predicted to be effective and long-lasting against a broad spectrum of pathotypes. However, the molecular mechanisms that control APR remain poorly understood. Here, quantitative trait loci (QTL) analysis of APR and fine mapping were performed on five barley populations derived from a common parent Vlamingh, which expresses APR to scald. Two QTLs, designated QSc.VR4 and QSc.BR7, were detected from a cross between Vlamingh and Buloke. Our data confirmed that QSc.VR4 is an effective and stable APR locus, residing on the short arm of chromosome 4H, and QSc.BR7 derived from Buloke may be an allele of reported Rrs2. High-resolution fine mapping revealed that QSc.VR4 is located in a 0.38 Mb genomic region between InDel markers 4H2282169 and 4H2665106. The gene annotation analysis and sequence comparison suggested that a gene cluster containing two adjacent multigene families encoding leucine-rich repeat receptor kinase-like proteins (LRR-RLKs) and germin-like proteins (GLPs), respectively, is likely contributing to scald resistance. Adult plant resistance (APR) governed by QSc.VR4 may confer partial levels of resistance to the fungus Rhynchosporium commune and, furthermore, be an important resource for gene pyramiding that may contribute broad-based and more durable resistance.
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http://dx.doi.org/10.1007/s00122-020-03599-9DOI Listing
July 2020

Short-form RON (sf-RON) enhances glucose metabolism to promote cell proliferation via activating β-catenin/SIX1 signaling pathway in gastric cancer.

Cell Biol Toxicol 2021 02 12;37(1):35-49. Epub 2020 May 12.

Department of Medical Oncology and Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore, sf-RON was proved to induce the β-catenin expression level through the AKT1/GSK3β signaling pathway. Meanwhile, the binding sites of β-catenin were identified in the promoter region of SIX1 and it was also demonstrated that β-catenin positively regulated SIX1 expression. SIX1 enhanced the promoter activity of key proteins in glucose metabolism, such as GLUT1 and LDHA. Results indicated that sf-RON regulated the cell proliferation and glucose metabolism of gastric cancer by participating in a sf-RON/β-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.
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http://dx.doi.org/10.1007/s10565-020-09525-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851020PMC
February 2021
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