Publications by authors named "Jinshou Yang"

12 Publications

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High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis.

J Hematol Oncol 2021 08 4;14(1):120. Epub 2021 Aug 4.

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100023, People's Republic of China.

Background: Pancreatic cancer's poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear.

Methods: Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis RESULTS: We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis.

Conclusions: These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis.
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http://dx.doi.org/10.1186/s13045-021-01131-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336101PMC
August 2021

Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review.

Cancer Commun (Lond) 2021 Jul 31. Epub 2021 Jul 31.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China.

Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Currently, screening is often applied in high-risk individuals to achieve the early diagnosis of pancreatic cancer. Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high-risk population and achieve early diagnosis and timely treatment of pancreatic cancer. Notably, accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) which is the golden standard for pancreatic cancer diagnosis. In addition, there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis of pancreatic cancer to be applied in the clinic. As the only serum biomarker approved by the United States Food and Drug Administration, carbohydrate antigen 19-9 (CA19-9) is not recommended to be used in the early screening of pancreatic cancer because of its limited specificity. Recently, increasing numbers of studies focused on the discovering of novel serum biomarkers and exploring their combination with CA19-9 in the detection of pancreatic cancer. Besides, the application of liquid biopsy involving circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes in blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis are drawing more and more attention. Furthermore, many innovative technologies such as artificial intelligence, computer-aided diagnosis system, metabolomics technology, ion mobility spectrometry (IMS) associated technologies, and novel nanomaterials have been tested for the early diagnosis of pancreatic cancer and have shown promising prospects. Hence, this review aims to summarize the recent progress in the development of early screening and diagnostic methods, including imaging, pathological examination, serological examination, liquid biopsy, as well as other potential diagnostic strategies for pancreatic cancer.
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http://dx.doi.org/10.1002/cac2.12204DOI Listing
July 2021

Comprehensive Analysis of Autophagy-Associated lncRNAs Reveal Potential Prognostic Prediction in Pancreatic Cancer.

Front Oncol 2021 26;11:596573. Epub 2021 May 26.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. Both long noncoding RNAs (lncRNAs) and autophagy play vital roles in the development and progress of PC. Here, we constructed a prognostic risk score system based on the expression profile of autophagy-associated lncRNAs for prognostic prediction in PC patients. Firstly, we extracted the expression profile of lncRNA and clinical information from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The autophagy-associated genes were from The Human Autophagy Database. Through Cox regression and survival analysis, we screened out seven autophagy-associated lncRNAs and built the risk score system in which the patients with PC were distinguished into high- and low-risk groups in both training and validation datasets. PCA plot displayed distinct discrimination, and risk score system displayed independently predictive value for PC patient survival time by multivariate Cox regression. Then, we built a lncRNA and mRNA co-expression network Cytoscape and Sankey diagram. Finally, we analyzed the function of lncRNAs in high- and low-risk groups by gene set enrichment analysis (GSEA). The results showed that autophagy and metabolism might make significant effects on PC patients of low-risk groups. Taken together, our study provides a new insight to understand the role of autophagy-associated lncRNAs and finds novel therapeutic and prognostic targets in PC.
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http://dx.doi.org/10.3389/fonc.2021.596573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188897PMC
May 2021

Construction of a prognostic model with histone modification-related genes and identification of potential drugs in pancreatic cancer.

Cancer Cell Int 2021 Jun 5;21(1):291. Epub 2021 Jun 5.

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100023, People's Republic of China.

Background: Pancreatic cancer (PC) is a highly fatal and aggressive disease with its incidence and mortality quite discouraging. An effective prediction model is urgently needed for the accurate assessment of patients' prognosis to assist clinical decision-making.

Methods: Gene expression data and clinicopathological data of the samples were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases. Differential expressed genes (DEGs) analysis, univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, random forest screening and multivariate Cox regression analysis were applied to construct the risk signature. The effectiveness and independence of the model were validated by time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier (KM) survival analysis and survival point graph in training set, test set, TCGA entire set and GSE57495 set. The validity of the core gene was verified by immunohistochemistry and our own independent cohort. Meanwhile, functional enrichment analysis of DEGs between the high and low risk groups revealed the potential biological pathways. Finally, CMap database and drug sensitivity assay were utilized to identify potential small molecular drugs as the risk model-related treatments for PC patients.

Results: Four histone modification-related genes were identified to establish the risk signature, including CBX8, CENPT, DPY30 and PADI1. The predictive performance of risk signature was validated in training set, test set, TCGA entire set and GSE57495 set, with the areas under ROC curve (AUCs) for 3-year survival were 0.773, 0.729, 0.775 and 0.770 respectively. Furthermore, KM survival analysis, univariate and multivariate Cox regression analysis proved it as an independent prognostic factor. Mechanically, functional enrichment analysis showed that the poor prognosis of high-risk population was related to the metabolic disorders caused by inadequate insulin secretion, which was fueled by neuroendocrine aberration. Lastly, a cluster of small molecule drugs were identified with significant potentiality in treating PC patients.

Conclusions: Based on a histone modification-related gene signature, our model can serve as a reliable prognosis assessment tool and help to optimize the treatment for PC patients. Meanwhile, a cluster of small molecule drugs were also identified with significant potentiality in treating PC patients.
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http://dx.doi.org/10.1186/s12935-021-01928-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178883PMC
June 2021

Reprogramming of Amino Acid Metabolism in Pancreatic Cancer: Recent Advances and Therapeutic Strategies.

Front Oncol 2020 29;10:572722. Epub 2020 Sep 29.

Department of General Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies with an extremely poor prognosis. Energy metabolism reprogramming, an emerging hallmark of cancer, has been implicated in the tumorigenesis and development of pancreatic cancer. In addition to well-elaborated enhanced glycolysis, investigating the role of reprogramming of amino acid metabolism has sparked great interests in recent years. The rewiring amino acid metabolism orchestrated by genetic alterations contributes to pancreatic cancer malignant characteristics including cell proliferation, invasion, metastasis, angiogenesis and redox balance. In the unique hypoperfused and nutrient-deficient tumor microenvironment (TME), the interactions between cancer cells and stromal components and salvaging processes including autophagy and macropinocytosis play critical roles in fulfilling the metabolic requirements and supporting growth of PDAC. In this review, we elucidate the recent advances in the amino acid metabolism reprogramming in pancreatic cancer and the mechanisms of amino acid metabolism regulating PDAC progression, which will provide opportunities to develop promising therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2020.572722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550743PMC
September 2020

GSTM3 Function and Polymorphism in Cancer: Emerging but Promising.

Cancer Manag Res 2020 20;12:10377-10388. Epub 2020 Oct 20.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Cancer is a major cause of human mortality; however, the molecular mechanisms and proteomic biomarkers that cause tumor progression in malignant tumors are either unknown or only partially revealed. Glutathione S-transferases mu3 (GSTM3), which belongs to a family of xenobiotic detoxifying phase II enzymes, is associated with carcinogen detoxification and the metabolism of exogenous electrophilic substances. It has been reported that GSTM3 has different polymorphisms in various tumor cells and regulates tumorigenesis, cell invasion, metastasis, chemoresistance, and oxidative stress. Deep research into the regulatory mechanisms involved in disorders of GSTM3 expression and the function of GSTM3 in different cancers may facilitate improvements in cancer prevention and targeted therapy. The combination of GSTM3 with other family members can regulate the carcinogenesis and susceptibility to different cancers in humans. GSTM3 also regulates the reactive oxygen species (ROS) and participates in oxidative stress-mediated pathology. Here, we provide a general introduction to GSTM3 in order to better understand the role of GSTM3 in cancer.
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http://dx.doi.org/10.2147/CMAR.S272467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585806PMC
October 2020

Glutathione S-Transferase Mu-3 Predicts a Better Prognosis and Inhibits Malignant Behavior and Glycolysis in Pancreatic Cancer.

Front Oncol 2020 28;10:1539. Epub 2020 Aug 28.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Pancreatic cancer (PC) is a lethal malignancy with an extremely unfavorable 5-year survival rate and a high mortality rate. Glutathione S-transferase mu-3 (GSTM3) has been shown to exert different functions in the progression and development of various cancers, except for PC. This study aimed to explore the role of GSTM3 in the malignant behavior and metabolic aspects of PC, its clinical significance, and its possible molecular mechanism in pancreatic cancer. Tumor microarrays of pancreatic ductal adenocarcinoma (PDAC) were used to evaluate the clinicopathological variables and GSTM3 expression by immunohistochemical staining. Kaplan-Meier survival and Cox regression analyses were further performed to assess the prognosis. The effect of GSTM3 on PC aggressiveness was detected using overexpressing and silencing transfection methods. Western blot, RT-qPCR, CCK-8, and cell cycle assay were applied to evaluate the expression level and proliferation. A xenograft animal model was assessed. Reactive oxygen species (ROS) were measured using the laser confocal scanner and glycolysis was detected using an Agilent Seahorse kit. RNA sequencing was used to assess the underlying mechanism and the signaling pathway involved. GSTM3 was relatively poorly expressed in PDAC tissues compared to para-tumoral tissues and a high level of GSTM3 indicated good overall survival. Functionally, overexpression of GSTM3 could significantly inhibit cell proliferation by delaying the G0/G1 transition, whereas the opposite results were found in the GSTM3 downregulation group. In addition, xenograft animal models further confirmed the effect on proliferation. Moreover, silencing of GSTM3 induced ROS accumulation and promoted glycolysis in PC, indicating its tumor suppressive effect, and vice versa when GSTM3 was upregulated. Finally, RNA sequencing results demonstrated that GSTM3 facilitates anti-tumorigenicity partly via the JAK-STAT signaling pathway in PC. GSTM3 inhibited tumor progression and altered the metabolic pattern in PC. This may be a potential predictive biomarker in PC and a prospective therapeutic target.
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http://dx.doi.org/10.3389/fonc.2020.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485563PMC
August 2020

The role of histone methylation in the development of digestive cancers: a potential direction for cancer management.

Signal Transduct Target Ther 2020 08 3;5(1):143. Epub 2020 Aug 3.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 100023, Beijing, PR China.

Digestive cancers are the leading cause of cancer-related death worldwide and have high risks of morbidity and mortality. Histone methylation, which is mediated mainly by lysine methyltransferases, lysine demethylases, and protein arginine methyltransferases, has emerged as an essential mechanism regulating pathological processes in digestive cancers. Under certain conditions, aberrant expression of these modifiers leads to abnormal histone methylation or demethylation in the corresponding cancer-related genes, which contributes to different processes and phenotypes, such as carcinogenesis, proliferation, metabolic reprogramming, epithelial-mesenchymal transition, invasion, and migration, during digestive cancer development. In this review, we focus on the association between histone methylation regulation and the development of digestive cancers, including gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, as well as on its clinical application prospects, aiming to provide a new perspective on the management of digestive cancers.
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http://dx.doi.org/10.1038/s41392-020-00252-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398912PMC
August 2020

Metabolism of pancreatic cancer: paving the way to better anticancer strategies.

Mol Cancer 2020 03 2;19(1):50. Epub 2020 Mar 2.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, PR China.

Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.
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http://dx.doi.org/10.1186/s12943-020-01169-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053123PMC
March 2020

OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2.

Mol Cancer Res 2020 05 4;18(5):685-697. Epub 2020 Feb 4.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several ligands, such as oxidized low-density lipoprotein, was previously reported in cardiovascular and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 expression was significantly higher in pancreatic cancer tissues than that in adjacent normal tissues and closely associated with reduced overall survival. OLR1 promoted proliferation and metastasis of pancreatic cancer cells and . Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1-c-Myc-HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1-c-Myc-HMGA2 axis. IMPLICATIONS: Our findings suggested that the OLR1-c-Myc-HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-0718DOI Listing
May 2020

Role of the microbiome in occurrence, development and treatment of pancreatic cancer.

Mol Cancer 2019 12 1;18(1):173. Epub 2019 Dec 1.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.

Pancreatic cancer is one of the most lethal malignancies. Recent studies indicated that development of pancreatic cancer may be intimately connected with the microbiome. In this review, we discuss the mechanisms through which microbiomes affect the development of pancreatic cancer, including inflammation and immunomodulation. Potential therapeutic and diagnostic applications of microbiomes are also discussed. For example, microbiomes may serve as diagnostic markers for pancreatic cancer, and may also play an important role in determining the efficacies of treatments such as chemo- and immunotherapies. Future studies will provide additional insights into the various roles of microbiomes in pancreatic cancer.
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http://dx.doi.org/10.1186/s12943-019-1103-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885316PMC
December 2019

The enhancement of glycolysis regulates pancreatic cancer metastasis.

Cell Mol Life Sci 2020 Jan 20;77(2):305-321. Epub 2019 Aug 20.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, People's Republic of China.

Pancreatic ductal adenocarcinoma is prone to distant metastasis and is expected to become the second leading cause of cancer-related death. In an extremely nutrient-deficient and hypoxic environment resulting from uncontrolled growth, vascular disturbances and desmoplastic reactions, pancreatic cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. Notably, pancreatic cancer cells show extensive enhancement of glycolysis, including glycolytic enzyme overexpression and increased lactate production, and this is caused by mitochondrial dysfunction, cancer driver genes, specific transcription factors, a hypoxic tumor microenvironment and stromal cells, such as cancer-associated fibroblasts and tumor-associated macrophages. The metabolic switch from oxidative phosphorylation to glycolysis in pancreatic cancer cells regulates the invasion-metastasis cascade by promoting epithelial-mesenchymal transition, tumor angiogenesis and the metastatic colonization of distant organs. In addition to aerobic glycolysis, oxidative phosphorylation also plays a critical role in pancreatic cancer metastasis in ways that remain unclear. In this review, we expound on the intracellular and extracellular causes of the enhancement of glycolysis in pancreatic cancer and the strong association between glycolysis and cancer metastasis, which we expect will yield new therapeutic approaches targeting cancer metabolism.
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http://dx.doi.org/10.1007/s00018-019-03278-zDOI Listing
January 2020
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