MMP11在浆液性卵巢癌中的表达、临床意义及其表位的预测

The expression, clinical significance and candidate epitopes of MMP11 in serous ovarian cancer

目的检测MMP11在正常卵巢组织与浆液性卵巢癌组织中的表达及临床意义,筛选用于设计抗肿瘤多肽疫苗的候选表位。方法免疫组织化学和GEPIA平台分析MMP11蛋白及mRNA在卵巢癌组织和正常卵巢组织中的表达,探讨其与浆液性卵巢癌患者的临床病理参数的关系;Kaplan Meier plotter分析MMP11 mRNA表达与患者预后的相关性;基因富集分析预测MMP11的功能;IEDB数据库及MOE分子模拟软件筛选潜在的MMP11的HLA-A*0201限制性表位。结果 MMP11 mRNA与蛋白在浆液性卵巢癌组织中表达水平显著高于正常组织(P<0.05)且与肿瘤分期、大小及淋巴结浸润相关;MMP11 mRNA表达水平高的患者总体生存期和无病生存期较短(P<0.05);MMP11主要富集于肿瘤相关通路与T细胞免疫功能相关基因子集;候选表位RV和LL具有与HLA-A*0201分子结合的潜力。结论 MMP11在浆液性卵巢癌的发生和发展中发挥重要作用,是一个潜在的浆液性卵巢癌的生物标志物和免疫治疗靶点。

Objective To detect the expression of MMP11 in normal ovarian tissue and serous ovarian cancer(SOC), to study the clinical significance of MMP11 in SOC, and further screen candidate epitopes for designing an anti-tumor epitope vaccine. Methods The expression of MMP11 protein and mRNA in SOC tissues and normal ovarian tissues was evaluated by immunohistochemistry and GEPIA. Kaplan-Meier plotter was used to analyze the correlation between MMP11 mRNA expression and prognosis of patients with SOC. Gene set enrichment analysis was used to predict the function of MMP11 in SOC. HLA-A*0201 restricted candidate epitopes derived from MMP11 were screened by IEDB database and MOE software. Results The expression level of MMP11 protein and mRNA was significantly upregulated in SOC compared with normal tissues and related to tumor stage, tumorsize, and lymphatic invasion. Overall survival(OS) and disease-free survival(DFS) were shorter in patients with high MMP11 mRNA expression. MMP11 were mainly enriched in cancer-associated pathways and T cell immune function-related gene subsets. The candidate epitopes(RV and LL) have the potential to bind to HLA-A*0201 molecules. Conclusion MMP11 plays an important role in the development of SOC and is a potential biomarker and immunotherapy target of SOC.