多队列分析揭示氯化物通道配体4在结肠癌中的表达和预后意义

Multi-cohort analysis reveals the expression and prognostic significance of chloride channel accessory 4 in colon cancer

目的与癌旁组织相比,氯化物通道配体4(chloride channel accessory 4,CLCA4)在多瘤种中存在差异表达,但在结肠癌中,其作为临床预后、免疫细胞浸润特征生物标志物的价值仍未被挖掘。方法本研究在癌症基因图谱队列、GSE32323队列、基因表达谱互作分析数据库和人类蛋白质图谱数据库中比较了肿瘤组织和正常组织中CLCA4的表达丰度。采用Cox回归分析CLCA4表达、临床病理特征与生存的关系;采用基因集富集分析探索CLCA4可能参与的肿瘤生物学行为;采用扩展的多维免疫组学特征算法和CIBERSORT算法评估CLCA4对肿瘤浸润免疫细胞分布的影响。结果CLCA4在结肠癌中表达下降提示不良预后;CLCA4低表达组和高表达组的肿瘤微环境中的12种免疫细胞成分存在显著差异;CLCA4在APC突变型患者中表达水平较低;CLCA4表达水平与核苷酸切除修复、DNA复制等生物学过程相关。结论CLCA4参与影响结肠癌微环境中的肿瘤浸润免疫细胞的分布,并可作为预后生物标志物。

Objective Compared with adjacent normal tissues,chloride channel accessory 4(CLCA4)is differentially expressed in multiple tumors,but in colon cancer,its value as a biomarker of clinical prognosis and immune cell infiltration characteristics has not been explored.Method We compared the expression abundance of CLCA4 in tumor tissues and normal tissues in the cancer genome atlas cohort,GSE32323 cohort,gene expression profiling interactive analysis database,and human protein atlas database.We used Cox regression to analyze the relationship between CLCA4 expression,clinicopathological characteristics,and survival.Gene set enrichment analysis was used to analyze the biological processes related to the expression abundance of CLCA4.Extended poly-dimensional immunome characterization algorithm and CIBERSORT algorithm were used to evaluate the impact of CLCA4 on the distribution of tumor-infiltrating immune cells.Result The decreased expression of CLCA4 in colon cancer suggested an unfavorable prognosis;there were significant differences in the twelve types of immune cells in the tumor microenvironment between the low expression group and the high expression group.CLCA4 expression abundance was lower in the APC mutant population.In addition,biological processes related to CLCA4 expression included nucleotide excision repair and DNA replication.Conclusion CLCA4 participated in affecting the distribution of tumor-infiltrating immune cells in the colon cancer microenvironment,and can be used as a prognostic biomarker.