引用本文:罗世波,吴江妮,丘新泽,梁志海,刘诗权.CLCA1在结直肠癌中的表达及其基因集富集分析[J].中国临床新医学,2021,14(7):675-679.
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CLCA1在结直肠癌中的表达及其基因集富集分析
罗世波,吴江妮,丘新泽,梁志海,刘诗权
530007 南宁,广西医科大学第二附属医院消化内科(罗世波,吴江妮,丘新泽,刘诗权);530021 南宁,广西医科大学第一附属医院消化内科(梁志海)
摘要:
[摘要] 目的 探讨钙激活的氯离子通道辅助蛋白1(CLCA1)在结直肠癌(CRC)中的表达及其与临床病理特征和预后的关系,分析其基因集富集情况。方法 通过肿瘤基因组图谱(TCGA)数据库下载CLCA1 mRNA表达数据,应用GSEA软件进行CLCA1不同表型的基因集富集分析。分析CLCA1 mRNA在CRC组织与癌旁组织中的差异表达,并分析其与临床病理特征的关联性。采用免疫组织化学染色法分析CLCA1在CRC组织和癌旁组织中的差异。结果 CRC组织中CLCA1表达较癌旁组织明显降低。CRC组织的免疫组织化学染色评分显著低于癌旁组织[(2.46±1.09)分 vs (5.65±0.49)分;t=6.458,P=0.000]。癌旁组织的CLCA1 mRNA表达水平显著高于临床Ⅰ~Ⅱ期CRC组织和临床Ⅲ~Ⅳ期CRC组织(P<0.05),临床Ⅰ~Ⅱ期CRC组织的CLCA1 mRNA表达水平显著高于临床Ⅲ~Ⅳ期CRC组织(P<0.05)。CLCA1高表达组临床分期为Ⅰ~Ⅱ期、N分期为N0期以及M分期为M0期的人数比例显著大于CLCA1低表达组(P<0.05)。CLCA1高表达组的生存预后显著优于CLCA1低表达组(χ2=8.200,P=0.004)。基因集富集分析结果显示,有19个基因集显著富集于CLCA1高表达表型,未发现有基因集显著富集于CLCA1低表达表型。结论 CLCA1在CRC组织中表达下调,并且与患者的临床病理特征及预后有关,具有作为CRC诊断、治疗和预后预测标志物的潜力。
关键词:  结直肠癌  钙激活的氯离子通道辅助蛋白1  诊断  预后  基因集
DOI:10.3969/j.issn.1674-3806.2021.07.08
分类号:R 735.3
基金项目:国家自然科学基金项目(编号:81460380);广西自然科学基金项目(编号:2017GXNSFAA198019,2020GXNSFAA159056)
Expression of CLCA1 in colorectal cancer and its gene set enrichment analysis
LUO Shi-bo, WU Jiang-ni, QIU Xin-ze, et al.
Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China
Abstract:
[Abstract] Objective To explore the expression of calcium-activated chloride channel regulator 1(CLCA1) in colorectal cancer(CRC) and its relationship with clinicopathological characteristics and prognosis, and to analyze its gene set enrichment. Methods The data of CLCA1 messenger RNA(mRNA) expression were downloaded from the Cancer Genome Atlas(TCGA) database, and the gene set enrichment analysis of different phenotypes of CLCA1 was performed by using GSEA software. The differential expression of CLCA1 mRNA between the CRC tissues and the adjacent tissues was analyzed, and its correlation with clinicopathological characteristics was analyzed. The difference of CLCA1 between the CRC tissues and the adjacent tissues was analyzed by immunohistochemistry. Results The expression of CLCA1 in the CRC tissues was significantly lower than that in the adjacent tissues. The immunohistochemical staining scores of the CRC tissues were significantly lower than those of the adjacent tissues[(2.46±1.09)scores vs (5.65±0.49)scores; t=6.458, P=0.000]. The level of CLCA1 mRNA expression in the adjacent tissues was significantly higher than that in the CRC tissues in clinical stage Ⅰ-Ⅱ and clinical stage Ⅲ-Ⅳ(P<0.05), and the level of CLCA1 mRNA expression in the CRC tissues in clinical stage Ⅰ-Ⅱ was significantly higher than that in the CRC tissues in clinical stage Ⅲ-Ⅳ(P<0.05). The proportion of the patients in the CLCA1 high expression group with clinical stage Ⅰ-Ⅱ, N0 stage(N staging) and M0 stage(M staging) was significantly greater than that in the CLCA1 low expression group(P<0.05). The survival prognosis of the CLCA1 high expression group was significantly better than that of the CLCA1 low expression group(χ2=8.200, P=0.004). The results of gene set enrichment analysis showed that 19 gene sets were significantly enriched in the CLCA1 high expression phenotypes, and that no gene sets were found to be significantly enriched in the CLCA1 low expression phenotypes. Conclusion CLCA1 is down-regulated in the CRC tissues and is related to the patients′ clinicopathological characteristics and prognoses. It has the potential as a marker for the diagnosis, treatment and outcome prediction of CRC.
Key words:  Colorectal cancer(CRC)  Calcium-activated chloride channel regulator 1(CLCA1)  Diagnosis  Prognosis  Gene set