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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2021, Vol. 10 ›› Issue (02) : 215 -219. doi: 10.3877/cma.j.issn.2095-3232.2021.02.020

所属专题： 文献；

基础研究

基于mRNA高通量测序的胆囊癌发病机制生物信息学研究
徐畅1, 王敬晗2, 程庆保2, 刘辰2, 胡明泰1, 罗祥基1, 姜小清2,†()   
  1. 1. 200438　上海，海军军医大学附属东方肝胆外科医院胆道三科
    2. 200438　上海，海军军医大学附属东方肝胆外科医院胆道一科
  • 收稿日期:2021-01-07 出版日期:2021-04-10
  • 通信作者: 姜小清

Bioinformatics study of pathogenesis of gallbladder cancer base on high-throughput mRNA sequencing

Chang Xu1, Jinghan Wang2, Qingbao Cheng2, Chen Liu2, Mingtai Hu1, Xiangji Luo1, Xiaoqing Jiang2,†()   

  1. 1. Department III of Biliary Tract Diseases, Shanghai Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai 200438, China
    2. Department Ⅰ of Biliary Tract Diseases, Shanghai Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai 200438, China
  • Received:2021-01-07 Published:2021-04-10
  • Corresponding author: Xiaoqing Jiang
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引用本文：

徐畅, 王敬晗, 程庆保, 刘辰, 胡明泰, 罗祥基, 姜小清. 基于mRNA高通量测序的胆囊癌发病机制生物信息学研究[J]. 中华肝脏外科手术学电子杂志, 2021, 10(02): 215-219.

Chang Xu, Jinghan Wang, Qingbao Cheng, Chen Liu, Mingtai Hu, Xiangji Luo, Xiaoqing Jiang. Bioinformatics study of pathogenesis of gallbladder cancer base on high-throughput mRNA sequencing[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(02): 215-219.

目的

基于mRNA高通量测序和生物信息学分析探讨胆囊癌发病机制。

方法

本研究选取2017年1月至2018年10月在上海东方肝胆外科医院就诊的10例胆囊癌患者。对其胆囊癌组织及癌旁正常组织进行mRNA高通量测序，并进行生物信息学分析。

结果

肿瘤组织与对应的癌旁正常组织相比，共鉴定出1 704个差异表达基因（DEGs），其中523个DEGs上调，1 181个DEGs下调。其中有674个DEGs显著富集到46个信号通路，包括PI3K-Akt、MAPK、Ras、Wnt等癌症相关信号通路，以及细胞运动相关通路，其中最显著的途径是神经活性配体- 受体相互作用信号途径，45个基因显著富集到钙信号通路。

结论

基于高通量mRNA测序和生物信息学技术分析显示胆囊癌和癌旁正常组织存在DEGs, 神经活性的配体- 受体相互作用信号通路改变最为显著，钙信号传导途径异常揭示了慢性结石性胆囊炎向胆囊癌转变的重要信号通路。

关键词: 胆囊肿瘤, 高通量核苷酸测序, RNA, 信使
Objective

To explore the pathogenesis of gallbladder carcinoma base on high-throughput mRNA sequencing and bioinformatics analysis.

Methods

10 patients with gallbladder carcinoma admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from January 2017 to October 2018 were recruited in this study. High-throughput mRNA sequencing and bioinformatics analysis were performed on the gallbladder carcinoma and paracancerous normal tissues.

Results

1 704 differentially-expressed genes (DEGs) were identified from tumor tissues and adjacent normal tissues, including 523 DEGs were up-regulated and 1 181 DEGs were down-regulated. Among them, 674 DEGs were significantly enriched on 46 signaling pathways, including PI3K-Akt, MAPK, Ras, Wnt and other cancer-related signaling pathways as well as cell movement-related signaling pathways, among which the most significant pathway was neuroactive ligand-receptor interaction signaling pathway, and 45 DEGs were significantly enriched on the calcium signaling pathway.

Conclusions

High-throughput mRNA sequencing and bioinformatics analysis demonstrate that DEGs exist in gallbladder cancer and adjacent normal tissues. The most significant changes are noted on the neuroactive ligand-receptor interaction signaling pathway. Abnormal calcium signaling pathway is noted as a critical signaling pathway for progression from chronic calculous cholecystitis to gallbladder cancer.

Key words: Gallbladder neoplasms, High-throughput nucleotide sequencing, RNA, messenger
图1 十例胆囊癌患者胆囊癌和癌旁组织差异表达基因火山图
表1 十例胆囊癌组织和癌旁正常组织的差异表达基因
序号 基因 log2 （fold change） P值 校正后 P值 变化
1 ADIPOQ -13.509 2.35E-27 4.16E-23 下调
2 TUSC5 -10.122 9.29E-18 5.75E-14 下调
3 PLP1 -5.923 9.73E-18 5.75E-14 下调
4 NRXN1 -4.928 8.73E-17 3.63E-13 下调
5 FABP4 -6.390 1.02E-16 3.63E-13 下调
6 CBLN4 -6.226 3.33E-16 9.85E-13 下调
7 PI16 -6.425 7.63E-16 1.93E-12 下调
8 PMP2 -6.949 1.31E-15 2.91E-12 下调
9 SCRG1 -3.738 1.69E-15 3.32E-12 下调
10 PLAC9 -3.409 4.04E-15 7.17E-12 下调
11 CHRDL1 -4.935 1.42E-14 2.30E-11 下调
12 PLIN1 -6.880 4.63E-14 6.84E-11 下调
13 GRIK3 -5.246 8.73E-14 1.19E-10 下调
14 FAM180B -6.128 2.61E-13 3.20E-10 下调
15 C2orf40 -4.997 2.71E-13 3.20E-10 下调
16 ………        
17 ………        
18 ………        
…… ………        
1692 ………        
1693 ………        
1694 ………        
1695 PNPLA3 1.859 0.008 757 0.049 212 上调
1696 GPM6B -1.291 0.008 766 0.049 229 下调
1697 TRIM72 1.996 0.008 771 0.049 230 上调
1698 P2RY8 -1.104 0.008 804 0.049 335 下调
1699 VSTM2B -2.950 0.008 807 0.049 341 下调
1700 SNED1 -1.077 0.008 813 0.049 359 下调
1701 C4BPB 1.636 0.008 943 0.049 824 上调
1702 LAMA1 1.744 0.008 955 0.049 854 上调
1703 HP 2.201 0.008 958 0.049 854 上调
1704 OVCH1 -1.554 0.008 984 0.049 954 下调
图2 胆囊癌患者样本中差异表达基因的无监督分层聚类热图
图3 胆囊癌患者样本中差异表达基因KEGG富集分析
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