Publications by authors named "Xudan Zhang"

9 Publications

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Rapid identification of papillary thyroid carcinoma and papillary microcarcinoma based on serum Raman spectroscopy combined with machine learning models.

Photodiagnosis Photodyn Ther 2021 Nov 21:102647. Epub 2021 Nov 21.

College of Software, Xinjiang University, Urumqi, 830046, China.; Key Laboratory of Signal Detection and Processing, Xinjiang University, Urumqi, 830046, China.; College of Information Science and Engineering, Xinjiang University, Urumqi, 830046, China.

Thyroid carcinoma is one kind of cancer with the highest diagnosis rate in the endocrine system, and its main histological subtype is papillary thyroid carcinoma (PTC) accounting for 80% of thyroid malignancies. In recent years, the incidence of thyroid cancer has increased exponentially, and its substantial increase was closely related to the overdiagnosis of papillary microcarcinoma (PMC). Therefore, early and accurate identification of PTC and PMC can prevent patients from being irreversibly damaged. This study aimed to identify PTC and PMC using Raman spectroscopy. We collected serum Raman spectra from 16 patients with PTC and 31 patients with PMC. Firstly, the collected imbalance data were preprocessed using the synthetic minority over-sampling technique (SMOTE). Then, the equalized data were dimensionality reduced by principal component analysis (PCA). Finally, the processed data were fed into the single decision tree (DT) classifier, as well as the random forest (RF) built on the idea of Boosting ensemble and the Adaptive Boosting (Adaboost) model built on the idea of Bagging ensemble for classification. The classification accuracy of the three models in the testing set were 75.38%, 81.54%, and 84.61%, respectively. Compared with the DT classifier, the accuracy of the models introducing the idea of ensemble learning was enhanced by 6.16% and 9.23%, respectively. The best model was the Adaboost. This result demonstrates that serum Raman spectroscopy combined with an ensemble learning algorithm was feasible in rapidly identifying PTC and PMC. At the same time, the method has great potential for application in the field of clinical diagnosis.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102647DOI Listing
November 2021

PLAGL2 promotes the proliferation and migration of gastric cancer cells via USP37-mediated deubiquitination of Snail1.

Theranostics 2021 1;11(2):700-714. Epub 2021 Jan 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No. 1277, Wuhan 430022, China.

PLAGL2 (pleomorphic adenoma gene like-2), a zinc finger PLAG transcription factor, is aberrantly expressed in several malignant tumors. However, the biological roles of PLAGL2 and its underlying mechanism in gastric cancer (GC) remain unclear. A series of experiments and were conducted to reveal the role of PLAGL2 in GC progression. The data revealed that PLAGL2 promotes GC cell proliferation, migration, invasion, and EMT and . Mechanistically, we demonstrated the critical role of PLAGL2 in the stabilization of snail family transcriptional repressor 1 (Snail1) and promoting Snail1-mediated proliferation and migration of GC cells. PLAGL2 activated the transcription of deubiquitinase USP37, which then interacted with and deubiquitinated Snail1 protein directly. In addition, GSK-3β-dependent phosphorylation of Snail1 protein is essential for USP37-mediated Snail1 deubiquitination regulation. In general, PLAGL2 promotes the proliferation and migration of GC cells through USP37-mediated deubiquitination of Snail1 protein. This work provided potential therapeutic targets for GC treatment.
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http://dx.doi.org/10.7150/thno.47800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738862PMC
August 2021

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers.

EBioMedicine 2020 Nov 20;61:103060. Epub 2020 Oct 20.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No. 1277, Wuhan, Hubei 430022, China. Electronic address:

Background: Although simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown.

Methods: A retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients.

Findings: Among the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour location, perineural invasion, the number of sampled lymph nodes (LNs) and positive LNs. The model showed good calibration and discrimination, with an AUC of 0.756 (95% CI, 0.722 to 0.789) in the primary cohort and 0.754 (95% CI, 0.715 to 0.793) in the validation cohort. After the addition of CEA and CA 72-4, the performance of pathology-based model was significantly improved in in both the primary cohort (AUC: 0.805 (0.774-0.835) vs. 0.756 (0.722-0.789), P < 0.001) and validation cohort (AUC: 0.796 (0.758-0.835) vs. 0.754 (0.715-0.793), P < 0.001). The results of decision curve analysis revealed that using our models to predict the status of MMR would add more benefit than either the detect-all-patients scheme or the detect-none scheme.

Interpretation: The models based on simplified clinicopathological features alone or in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients.
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http://dx.doi.org/10.1016/j.ebiom.2020.103060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578682PMC
November 2020

MicroRNA-214-3p targets the PLAGL2-MYH9 axis to suppress tumor proliferation and metastasis in human colorectal cancer.

Aging (Albany NY) 2020 05 15;12(10):9633-9657. Epub 2020 May 15.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obviously downregulated in CRC. Moreover, we found a strong correlation between the miR-214-3p level and tumor size and lymphatic metastasis. Furthermore, when miR-214-3p was decreased by an Lv-miR-214-3p inhibitor, the proliferation and migration of SW480 and HCT116 cells were significantly increased. As expected, the ability of proliferation and migration was significantly suppressed when miR-214-3p was overexpressed in DLD1 cells. According to the dual-luciferase reporter results, PLAGL2 was found to be a direct downstream molecule of miR-214-3p. Chromatin immunoprecipitation (CHIP) confirmed that MYH9, a well-known cytoskeleton molecule in CRC, was a direct targeting gene of PLAGL2. Silencing PLAGL2 or MYH9 could reverse the effect of a miR-214-3p inhibitor on CRC cells. In summary, our studies proved that low expression of miR-214-3p and overexpression of downstream PLAGL2 in CRC indicated a poor prognosis. MiR-214-3p suppressed the malignant behaviors of colorectal cancer by regulating the PLAGL2/MYH9 axis. MiR-214-3p might be a novel therapeutic target or prognostic marker for CRC.
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http://dx.doi.org/10.18632/aging.103233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288958PMC
May 2020

PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1.

Br J Cancer 2020 02 12;122(4):578-589. Epub 2019 Dec 12.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: We previously demonstrated that the pleomorphic adenoma gene like-2 (PLAGL2) is involved in the pathogenesis of Hirschsprung disease. Enhanced PLAGL2 expression was observed in several malignant tumours. However, the exact function of PLAGL2 and its underlying mechanism in colorectal cancer (CRC) remain largely unknown.

Methods: Immunohistochemical analysis of PLAGL2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of PLAGL2 in the progression of CRC.

Results: Enhanced PLAGL2 expression was significantly associated with EMT-related proteins in CRC. The data revealed that PLAGL2 promotes CRC cell proliferation, migration, invasion and EMT both in vitro and in vivo. Mechanistically, PLAGL2 promoted the expression of ZEB1. PLAGL2 enhanced the expression and nuclear translocation of β-catenin by decreasing its phosphorylation. The depletion of β-catenin neutralised the regulation of ZEB1 that was caused by enhanced PLAGL2 expression. The small-molecule inhibitor PNU-74654, also impaired the enhancement of ZEB1 that resulted from the modified PLAGL2 expression. The depletion of ZEB1 could block the biological function of PLAGL2 in CRC cells.

Conclusions: Collectively, our findings suggest that PLAGL2 mediates EMT to promote colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1.
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http://dx.doi.org/10.1038/s41416-019-0679-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028997PMC
February 2020

Increased miR-214 expression suppresses cell migration and proliferation in Hirschsprung disease by interacting with PLAGL2.

Pediatr Res 2019 10 1;86(4):460-470. Epub 2019 Mar 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: The miR-214 has been reported to be associated with various diseases, but its involvement in the pathophysiology of Hirschsprung disease (HSCR) is almost completely unexplored.

Methods: In our study, we conducted a series of experiments to unravel the biological role of miR-214 in the pathophysiology of HSCR. qRT-PCR and western blotting were utilized to investigate the relative expression levels of miR-214, mRNAs, and proteins of related genes in colon tissues from 20 controls without HSCR and 24 patients with HSCR. The potential biological role of miR-214 in two cell lines (SKN-SH and SH-SY5Y) was assessed using the CCK8 assay, EdU staining, transwell assay, and flow cytometry. The dual-luciferase reporter assay was used to confirm PLAGL2 as a common target gene of miR-214.

Results: All results suggested that miR-214 is upregulated in HSCR tissue samples compared with controls. Additionally, we found that miR-214 could inhibit cell proliferation and migration by directly downregulating the expression of PLAGL2, and the extent of the miR-214-mediated inhibitory effects could be rescued by a PLAGL2 overexpression plasmid.

Conclusion: Our results revealed that miR-214 is indeed involved in the pathophysiology of HSCR and suppresses cell proliferation and migration by directly downregulating PLAGL2 in cell models.
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http://dx.doi.org/10.1038/s41390-019-0324-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768286PMC
October 2019

Downregulation of DAPK1 promotes the stemness of cancer stem cells and EMT process by activating ZEB1 in colorectal cancer.

J Mol Med (Berl) 2019 01 20;97(1):89-102. Epub 2018 Nov 20.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) play an important role in the metastasis and chemoresistance in the context of colorectal cancer (CRC). Downregulation of death associated protein kinase 1 (DAPK1) may promote metastasis and chemoresistance of cancer cells through various mechanisms. However, the association between DAPK1 and CSCs or EMT has not been explored. In this study, we demonstrated that DAPK1 was associated with elevated stemness of CSCs in patients with CRC. Silencing of DAPK1 in CRC cell lines promoted the metastasis and chemoresistance due to increased stemness of CSCs and enhanced mesenchymal phenotype, an effect that was mediated via activation of the transcription factor, zinc finger E-box binding homeobox 1 (ZEB1). Blockade of this signaling pathway attenuated the stemness of CSCs and rescued the EMT process. DAPK1-ZEB1 may lie at the interface of TGF-β and WNT pathways and participate in both CSCs and EMT process. Targeted therapies aimed at DAPK1-ZEB1 pathway may inhibit the chemoresistance and metastasis of CRC. KEY MESSAGES: Downregulation of DAPK1 promotes chemoresistance and metastasis of CRC. Inhibition of DAPK1 promotes the stemness of cancer stem cells and EMT process. DAPK1-ZEB1 may lie at the interface of TGF-β and WNT pathways. DAPK1-ZEB1 participates in both CSCs and EMT process.
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http://dx.doi.org/10.1007/s00109-018-1716-8DOI Listing
January 2019

Nuclear factor I/B promotes colorectal cancer cell proliferation, epithelial-mesenchymal transition and 5-fluorouracil resistance.

Cancer Sci 2019 Jan 8;110(1):86-98. Epub 2018 Dec 8.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Nuclear factor I/B (NFIB) is a widely studied transcription factor that participates in tumor progression; nevertheless, studies on NFIB in colorectal cancer (CRC) are limited. In our study, Western blot and RT-PCR analyses showed that NFIB was overexpressed in CRC tissues and cell lines, which was consistent with our bioinformatic analysis results. Furthermore, NFIB expression was closely related to the TNM stage of CRC. NFIB promoted cell proliferation and migration and inhibited cell apoptosis in vitro. Meanwhile, we discovered that NFIB accelerated xenograft tumor growth in vivo. In addition, NFIB weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU). NFIB induced epithelial-mesenchymal transition (EMT) by upregulating snail expression, which was accompanied by decreased E-cadherin and Zo-1 expression and increasedd Vimentin expression. Because the Akt pathway plays an important role in CRC progression, we examined whether there was a correlation between NFIB and the Akt pathway in cell proliferation and migration. Our results showed that NFIB promoted cell proliferation and increased 5-FU resistance by activating the Akt pathway. In summary, our findings suggested that NFIB induced EMT of CRC cells via upregulating snail expression and promoted cell proliferation and 5-FU resistance by activating the Akt pathway.
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http://dx.doi.org/10.1111/cas.13833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317934PMC
January 2019

Correlation of metastasis characteristics with prognosis in gastric mixed adenoneuroendocrine carcinoma: Two case reports.

Medicine (Baltimore) 2017 Dec;96(50):e9189

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Rationale: This article is aimed to retrospect the clinicopathological data of 2 cases of gastric MANENCs. MANEC is a rare biphasic tumor type that is coexistence of dual neuroendocrine and adenocarcinoma differentiation with each composing exceeding 30% volume. Gastric MANEC have just been reported anecdotally in the literature due to their rarity and heterogeneity. According to our study, these neoplasms have 3 different metastasis patterns: only adenocarcinomatous or neuroendocrine carcinoma and both of the 2 components. We first focus on the correlation of metastasis characteristics with prognosis in gastric MANEC, which may be potential implications for the choice of chemotherapy.

Patient Concerns: The 2 cases of patient shared several symptoms: epigastric discomfort, weight loss, hematemesis, or melena.

Diagnosis: The 2 patients were diagnosis as MANEC based on the identification of histopathological analysis. In case 1, the poor differentiated adenocarcinoma accounted for 30%, the neuroendocrine part account for 70% and both of the 2 components metastasized to the lymph nodes, whereas in case 2, poorly differentiated adenocarcinoma accounted for 70%, the neuroendocrine part for 30% and only the glandular component invaded regional lymph nodes.

Interventions: The first patient underwent laparoscopic radical gastrectomy and underwent adjuvant chemotherapy, combination of cisplatin, and etoposide successfully. The second patient received radical gastronomy, and did not receive any chemotherapy due to general weakness.

Outcomes: The first patient is alive with no evidence of recurrence, and the second patient died 6 months after the operation.

Lessons: The assessment of metastatic sites should be a routine pathological practice, which is crucial for clinical decision-making and the selection of management.
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http://dx.doi.org/10.1097/MD.0000000000009189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815743PMC
December 2017
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