Wei Haotang, Tang Li, Wang Jialei, Ni Min, Liao Xiwen, Guo Erna
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Guangxi Medical University, 530031, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
J Cancer. 2023 Jun 4;14(9):1607-1622. doi: 10.7150/jca.83423. eCollection 2023.
The main purpose of this study is to perform a comprehensive investigation of the prognostic value and molecular mechanism of syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1) through the whole genome RNA sequencing data of the The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort. There were 438 COAD patients were fit into current study for survival analysis. Gene expression profiling interactive analysis 2.0, Database for Annotation, Visualization and Integrated Discovery v6.8, gene set enrichment analysis (GSEA) and connectivity map (CMap) are used to investigate the molecular mechanisms and targeted drugs of STXBP5-AS1 in COAD. By comparing the expression level of tumor and non-tumor tissues, we found that STXBP5-AS1 was notablely down-regulated in COAD tumor tissues. Survival analysis suggested that low STXBP5-AS1 expression was significantly related to poor overall survival (OS) of COAD (log-rank P=0.035, adjusted P=0.005, HR=0.545, 95%CI=0.356-0.836). The enrichment analysis of STXBP5-AS1 co-expressed genes, GSEA and differentially expressed genes suggests that STXBP5-AS1 may play a part in COAD by regulating the following biological processes or pathways: cell junction, DNA replication, apoptosis, cell cycle, metastasis, tumor protein 53, Wnt, mTORC1, MCM, notch receptor 4, transforming growth factor beta receptor, and cGMP-PKG signaling pathway. CMap analysis was screened out four small molecule drugs (anisomycin, cephaeline, NU-1025 and quipazine) that may be used as STXBP5-AS1 targeted therapy drugs in COAD. The co-expression analysis of STXBP5-AS1 and immune cell gene signature indicated that STXBP5-AS1 was significantly related to immune cell gene set in normal intestinal tissues, but not in COAD tumor tissues. Our results revealed that STXBP5-AS1 is notablely down-regulated in COAD tumor tissues, and may act as a novel prognostic biomarker for COAD.
本研究的主要目的是通过癌症基因组图谱（TCGA）结肠腺癌（COAD）队列的全基因组RNA测序数据，对 syntaxin 结合蛋白5反义RNA 1（STXBP5-AS1）的预后价值和分子机制进行全面研究。有438例COAD患者纳入本研究进行生存分析。使用基因表达谱交互式分析2.0、注释、可视化和综合发现数据库v6.8、基因集富集分析（GSEA）和连通性图谱（CMap）来研究STXBP5-AS1在COAD中的分子机制和靶向药物。通过比较肿瘤组织和非肿瘤组织的表达水平，我们发现STXBP5-AS1在COAD肿瘤组织中显著下调。生存分析表明，低STXBP5-AS1表达与COAD的总体生存期（OS）差显著相关（对数秩检验P=0.035，校正P=0.005，HR=0.545，95%CI=0.356-0.836）。对STXBP5-AS1共表达基因、GSEA和差异表达基因的富集分析表明，STXBP5-AS1可能通过调节以下生物学过程或途径在COAD中发挥作用：细胞连接、DNA复制、细胞凋亡、细胞周期、转移、肿瘤蛋白53、Wnt、mTORC1、MCM、Notch受体4、转化生长因子β受体和cGMP-PKG信号通路。CMap分析筛选出四种小分子药物（茴香霉素、头花千金藤碱、NU-1025和喹哌嗪），它们可能用作COAD中STXBP5-AS1的靶向治疗药物。STXBP5-AS1与免疫细胞基因特征的共表达分析表明，STXBP5-AS1在正常肠道组织中与免疫细胞基因集显著相关，但在COAD肿瘤组织中并非如此。我们的结果表明，STXBP5-AS1在COAD肿瘤组织中显著下调，可能作为COAD的一种新的预后生物标志物。
