目的 检测PP1A与GSDME在结直肠癌组织中的表达与CD8+T淋巴细胞丰度,探讨PP1A与GSDME介导焦亡的相关性和临床意义.方法 应用GEPIA数据库分析PP1A与GSDME在结直肠癌组织与正常组织中mRNA的表达.采用Western blot法检测结直肠癌组织与对应癌旁正常黏膜中PP1A蛋白表达水平,运用免疫组化法检测107例结直肠癌与癌旁正常黏膜中PP1A、GSDME蛋白的表达和CD8+T淋巴细胞丰度.利用Spearman等级相关性分析PP1A、GSDME和CD8+T淋巴细胞丰度的相关性.结果 GEPIA数据库检索显示,PP1A与GSDME的mRNA在结直肠癌组织和正常组织中的表达差异有统计学意义(P＜0.05).Western blot法检测结果显示,结直肠癌组织中PP1A相对表达量明显高于癌旁组织(0.937 vs 0.643,P＜0.001).免疫组化结果显示,结直肠癌组织中PP1A的表达明显高于正常黏膜,而GSDME的表达明显低于正常黏膜(P＜0.05),GSDME表达与结直肠癌患者年龄、临床分期和错配修复蛋白密切相关(P＜0.05);CD8+T细胞在癌浸润前沿的分布明显高于癌旁正常黏膜,且CD8+T细胞在癌组织中的分布与pT分期、临床分期及淋巴结转移相关.Spearman相关性分析显示,PP1A与GSDME表达呈负相关(r=-0.196,P＜0.05).PP1A阳性结直肠癌患者的总生存期低于PP1A阴性患者(P＜0.05),患者预后与分化程度、淋巴结转移、pT分期和临床分期相关.PP1A表达、肿瘤分化程度、临床分期、pT分期和淋巴结转移均是影响结直肠癌患者预后的独立危险因素.结论 PP1A在结直肠癌中高表达,与GSDME介导的细胞焦亡呈负相关,两者表达差异性与结直肠癌的发生、发展及预后均密切相关,可作为判断结直肠癌患者预后的潜在指标,CD8+T细胞的差异性分布可能与GSDME介导的细胞焦亡及肿瘤的发展相关.
Clinical significance of PP1A and GSDME mediated pyroptosis in colorectal cancer
Purpose To detect the expression of PP1A and GSDME and the abundance of CD8+T lymphocytes in colorectal cancer,and to explore the correlation and clinical significance of PP1A and GSDME mediated pyroptosis.Methods GEPIA da-tabase was applied to analyze the mRNA expression of PP1A and GSDME in colorectal cancer and normal tissues.Western blot assay was used to detect the expression of PP1A in colorectal cancer and the corresponding normal mucosa.Immunohisto-chemistry was applied to detect the expression of PP1A and GS-DME and CD8+T lymphocytes abundance in 107 colorectal car-cinomas and normal mucosa adjacent to the carcinomas.Spearman rank correlation was used to analyze the correlation between PP1A,GSDME and CD8+T cells abundance.Results The GEPIA database search showed that mRNA expression of PP1A and GSDME in colorectal cancer differed compared to normal tissues(P＜0.05).Western blot analysis showed that the relative expression of PP1A in colorectal cancer tissue was significantly higher than that in para-cancerous tissues(0.937 vs 0.643,P＜0.001).Immunohistochemical results showed that the expression of PP1A in colorectal cancer tissues was signifi-cantly higher than that in normal mucosa(P＜0.05).The ex-pression of GSDME in cancer tissue was closely correlated with patients'age,clinical stage and mismatch repair proteins(P＜0.05),and the distribution of CD8+T cells in the cancer infil-tration front was significantly higher than that in the normal mu-cosa,and the distribution of CD8+T cells in the cancer was cor-related with pT stage,clinical stage and lymph node metastasis.Spearman correlation analysis showed that PP1A was negatively correlated with GSDME expression(r=-0.196,P＜0.05).The overall survival PP1A-positive colorectal cancer patients was worse than that of PP1A-negative patients(P＜0.05),and the prognosis of patients was correlated with the degree of differentia-tion,lymph node metastasis,pT stage and clinical stage.Posi-tive expression of PP1A,degree of differentiation,clinical stage,pT stage and lymph node metastasis are independent risk factors affecting the prognosis of colorectal cancer patients.Conclusion PP1A is highly expressed in colorectal cancer and negatively correlated with GSDME-mediated cell pyroptosis,and the differ-ential expression of both is closely related to the progression and prognosis of colorectal cancer,which can be used as a potential indicator for judgment of the prognosis of colorectal cancer pa-tients.The differential distribution of CD8+T cells may be asso-ciated with GSDME-mediated cell pyroptosis and tumor develop-ment.
万方数据
维普
