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鉴定控制胃癌中癌症干细胞特征的关键基因。

Identification of key genes controlling cancer stem cell characteristics in gastric cancer.

作者信息

Huang Chao, Hu Ce-Gui, Ning Zhi-Kun, Huang Jun, Zhu Zheng-Ming

机构信息

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.

出版信息

World J Gastrointest Surg. 2020 Nov 27;12(11):442-459. doi: 10.4240/wjgs.v12.i11.442.

DOI:10.4240/wjgs.v12.i11.442
PMID:33304447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7701879/
Abstract

BACKGROUND

Self-renewal of gastric cancer stem cells (GCSCs) is considered to be the underlying cause of the metastasis, drug resistance, and recurrence of gastric cancer (GC).

AIM

To characterize the expression of stem cell-related genes in GC.

METHODS

RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database, and the results of the GC mRNA expression-based stemness index (mRNAsi) were analyzed. Weighted gene coexpression network analysis was then used to find modules of interest and their key genes. Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter, and the online database Oncomine was used to assess the expression of key genes in GC.

RESULTS

mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues ( < 0.0001). A total of 16 modules were obtained from the gene coexpression network; the brown module was most positively correlated with mRNAsi. Sixteen key genes (, , , , , , , , , , , , , , , and ) were identified in the brown module. The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component, the sister chromatid segregation biological process, the motor activity molecular function, and the cell cycle and homologous recombination pathways. Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes (, and ) were consistently related.

CONCLUSION

Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics. , , and are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.

摘要

背景

胃癌干细胞(GCSCs)的自我更新被认为是胃癌(GC)转移、耐药和复发的根本原因。

目的

表征GC中干细胞相关基因的表达。

方法

从癌症基因组图谱数据库获得胃腺瘤和腺癌样本的RNA测序结果及临床数据,并分析基于GC mRNA表达的干性指数(mRNAsi)结果。然后使用加权基因共表达网络分析来寻找感兴趣的模块及其关键基因。使用在线工具Kaplan-Meier Plotter对关键基因进行生存分析,并使用在线数据库Oncomine评估关键基因在GC中的表达。

结果

与正常胃组织相比,GC组织中的mRNAsi显著上调(<0.0001)。从基因共表达网络中获得了总共16个模块;棕色模块与mRNAsi的正相关性最高。在棕色模块中鉴定出16个关键基因(,,,,,,,,,,,,,,,和)。功能和通路富集分析表明,关键基因在纺锤体细胞成分、姐妹染色单体分离生物学过程、运动活性分子功能以及细胞周期和同源重组通路中显著富集。生存分析和Oncomine分析显示,GC患者的预后与三个基因(,和)的表达始终相关。

结论

16个关键基因主要与干细胞自我更新和细胞增殖特征相关。,和是抑制GC细胞干性特征最有可能的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/9785198caf23/WJGS-12-442-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/59a9626e7a79/WJGS-12-442-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/f75e4c363f74/WJGS-12-442-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/49f11a7715a7/WJGS-12-442-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/e6669dcd81be/WJGS-12-442-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/63b4041aa1bd/WJGS-12-442-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/9785198caf23/WJGS-12-442-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/59a9626e7a79/WJGS-12-442-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/f75e4c363f74/WJGS-12-442-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/49f11a7715a7/WJGS-12-442-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/e6669dcd81be/WJGS-12-442-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/63b4041aa1bd/WJGS-12-442-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a8/7701879/9785198caf23/WJGS-12-442-g006.jpg

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