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中国癌症防治杂志

中国癌症防治杂志 ›› 2022, Vol. 14 ›› Issue (2): 160-166.doi: 10.3969/j.issn.1674-5671.2022.02.05

• 临床研究 • 上一篇    下一篇

基于转录组测序分析弥漫型胃癌特征及其核心基因LUM的表达 

  

  1. 广西医科大学附属肿瘤医院胃肠外科 
  • 出版日期:2022-04-25 发布日期:2022-05-07
  • 通讯作者: 覃宇周 E-mail：qyz402@126.com；黄名威 E-mail：hmw503@163.com
  • 基金资助:
    国家自然科学基金项目（81760521）；广西自然科学基金项目（2021GXNSFAA220036）

Analysis of the characteristics of diffuse gastric cancer and expression of hub gene LUM based on transcriptome sequencing

  • Online:2022-04-25 Published:2022-05-07

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摘要： 目的 分析弥漫型胃癌的转录组特征并对核心基因LUM（Lumican）的表达进行验证。方法 收集2021年1月—2021年12月广西医科大学附属肿瘤医院手术切除的29例胃癌患者癌组织及其配对癌旁正常组织标本，取其中5例弥漫型胃癌组织进行转录组测序并获取基因表达谱，再利用差异基因进行GO和KEGG富集分析，使用cytoscape软件对差异基因进行蛋白互作网络构建，评估优势基因集。利用TCGA数据库中胃癌相关的转录组和临床数据进行基因集表达量及预后分析。采用RT-qPCR检测另外24例胃癌组织中核心基因LUM的表达水平。结果 与配对癌旁正常组织相比，弥漫型胃癌组织中有175个差异基因，其中上调和下调基因分别有91和84个。GO和KEGG富集分析显示，弥漫型胃癌以多种方式参与细胞外基质相关的细胞过程和恶性进展。弥漫型胃癌中的优势基因集为上皮-间充质转化（epithelial-mesenchymal transition，EMT）相关基因集，该基因集中COL6A3、LUM、COL1A2、SPARC、COL1A1、CDH11、COL3A1、NID2、BGN和COL4A1的表达水平较癌旁正常组织和肠型胃癌组织高（均P<0.05）。核心基因LUM高表达的弥漫型胃癌患者总生存期缩短（P=0.043）。RT-qPCR检测结果显示，LUM在胃癌组织中高表达，且在弥漫型胃癌中的表达水平高于肠型和混合型（均P<0.05）。结论 弥漫型胃癌的转录组特征表现为EMT相关基因集处于优势地位，其核心基因LUM在弥漫型胃癌中表达增强且高表达患者总生存期缩短，LUM可能是弥漫型胃癌潜在的预测标志物和治疗靶点。

关键词: 胃肿瘤, 弥漫型胃癌, 转录组测序, 上皮-间充质转化, LUM

Abstract:  Objective To analyze the transcriptome signatures of diffuse gastric cancer (DGC) and the expression of hub gene LUM (Lumican). Methods A total of 29 gastric cancer (GC) tissue and their corresponding adjust normal tissue samples were collected from patients who underwent GC resection between January 2021 and December 2021 at Guangxi Medical University Cancer Hospital, of which 5 were used to obtain mRNA expression profiling of DGC by RNA sequencing (RNA-Seq). Differentially expressed genes (DEGs) were analyzed by GO and KEGG. The protein-protein interaction (PPI) network of DEGs was constructed by cytoscape, and then the dominant gene set was evaluated. Based on the transcriptome and clinical data of GC in TCGA database, the gene expression and the prognosis were analyzed. RT-qPCR was used to examine the expression of hub gene LUM in other 24 GC tissues. Results Compared with normal adjacent tissues, a total of 175 DEGs in DGC, of which 91 genes were up-regulated and 84 genes were down-regulated. GO and KEGG enrichment analysis revealed that there were multiple ways involved in extracellular matrix related cellular processes and malignant progression in DGC. The EMT-associated gene set was dominant in DGC. The expression levels of COL6A3, LUM, COL1A2, SPARC, COL1A1, CDH11, COL3A1, NID2, BGN and COL4A1 in the EMT-associated gene set were higher than those in the adjacent normal and intestinal GC (all P<0.05). DGC patients with high expression of the hub gene LUM had a shorter overall survival (P=0.043). The RT-qPCR results showed that LUM was highly expressed in GC, and the expression level in DGC was higher than that in the intestinal and mixed GC(all P<0.05). Conclusions The transcriptome characteristics of DGC shows that EMT-associated gene set is in a dominant position. The expression of hub gene LUM is increased in DGC and the overall survival of patients with high LUM expression is shortened. LUM can be used as a potential prognostic marker and therapeutic target for DGC.

Key words: Gastric cancer, Diffuse gastric cancer, RNA sequencing, EMT, LUM

中图分类号: 

  • R735.2