ATP5A1在结肠癌中的表达及临床意义

Expression and significance of ATP5A1 in colon cancer

目的 分析ATP5A1在结肠癌中的表达情况及其意义,研究ATP5A1表达变化导致结肠癌细胞分子及功能改变的机制,为针对结肠癌的精准治疗提供依据。方法 采用免疫组化结合生存期组织芯片研究ATP5A1在结肠癌及癌旁组织的表达变化及其与临床病理特征的关系,结合TCGA数据库分析ATP5A1表达改变对结肠癌生存率的影响。采用高分辨质谱分析ATP5A1表达改变对结肠癌总蛋白表达的影响。采用CCK-8法分析ATP5A1表达改变对氧化磷酸化通路不同抑制剂的影响。结果 ATP5A1在结肠癌组织中的表达水平高于对应癌旁组织,而患者的ATP5A1高表达预示着较长时间的生存期。蛋白质组学分析发现,随着ATP5A1表达增加,结肠癌细胞各呼吸链复合物都有不同程度的表达上调,尤以复合物II中的SDHB蛋白表达增高最为显著。TTFA和oligomycin A在低表达ATP5A1和SDHB的细胞系中表现出更明显的抑制细胞增殖的能力。结论 氧化磷酸化呼吸链的不同组分间的协同变化反映了结肠癌存在线粒体重塑现象,研究该现象有助于针对结肠癌采用更精准的治疗策略。

Objective To analyze the expression changes and significance of ATP5A1 in colon cancer,to study the molecular and functional mechanism of colon cancer cells caused by the changes in ATP5A1 expression,and to provide a basis for precision treatment of colon cancer.Methods The expression changes of ATP5A1 in colon cancer and the relationship with clinical pathological characteristics were studied by immunohistochemistry and survival tissue microarray.The influence of ATP5A1 expression on survival rate of colon cancer was analyzed with TCGA database.High resolution mass spectrometry was used to analyze the effects of ATP5A1 expression changes on total protein expression of colon cancer cells.Cck-8 assay was used to analyze the effect of ATP5A1 expression changes on different inhibitors of oxidative phosphorylation pathway.Results The ATP5A1 expression increased significantly in colon cancer tissue compared with the corresponding adjacent normal tissue,and high ATP5A1 expression in patients predicted a longer survival.Proteomic analysis showed that with the increase of ATP5A1 expression,each respiratory chain in colon cancer cells were up-regulated to varying degrees,especially SDHB protein expression increased most significantly in complex II.TTFA and olgomycin A were found to inhibit cell proliferation to a greater extent in cell lines with lower expression ATP5A1 and SDHB.Conclusion The synergetic changes among different components of the oxidative phosphorylation respiratory chain reflect the mitochondrial remodeling in colon cancer,and the study of this phenomenon is helpful to put forward a more precise treatment strategy for colon cancer.