Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu, Sichuan, P.R. China.
Department of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, Sichuan P.R. China.
Bioengineered. 2021 Dec;12(1):1676-1688. doi: 10.1080/21655979.2021.1921551.
Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker. Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.
结直肠癌(CRC)是最常见的肿瘤之一,在全球癌症死亡原因中排名第二。晚期患者的预后仍然很差。在这项研究中,我们基于基因表达综合数据库中结直肠癌表达数据,通过加权基因共表达网络分析,鉴定出与肿瘤浸润免疫细胞关联度最高的枢纽模块。接下来,通过共表达网络和预后分析,鉴定出三个与浸润免疫细胞相关的枢纽基因(ADAM8、IL-1A、VAV3)。通过 TIMER 数据库的分析验证,选择 ADAM8 作为预后生物标志物。最后,功能试验结果表明,下调 ADAM8 基因表达部分逆转了 CRC 细胞对 TIL 的免疫耐受。通过生物信息学分析方法和实验技术,我们将 ADAM8 鉴定为与 CRC 肿瘤浸润免疫细胞相关的预后生物标志物和临床治疗靶点。