AGR2在三阴性乳腺癌中免疫调控功能及其潜在的预后价值分析

The Immune Functional and Prognostic Analysis of AGR2 in Triple-negative Breast Cancer

目的乳腺癌是我国女性最常见、发病率最高的恶性肿瘤,其又以三阴性乳腺癌预后最差、临床治疗较困难。本研究旨在分析三阴性乳腺癌基因表达数据,寻找免疫相关预后有关的三阴性乳腺癌的潜在标志物。方法通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库,分析三阴性乳腺癌和正常组织基因表达数据,筛选差异表达基因及功能并分析其对生存预后的意义。通过GEPIA2(gene expression profiling interactive analysis)数据库对具有预后意义的差异表达基因进一步分析其对乳腺癌分子分型的特异性。对具有预后相关的三阴性乳腺癌特异性基因分析其免疫意义。结果本研究共获得三阴性乳腺癌差异表达基因972个,其中具有预后意义的差异表达基因共27个,其中显著下调基因前梯度蛋白2(anterior gradient 2,AGR2)和显著上调基因S100钙结合蛋白B(S100 calcium binding protein B,S100B)具有三阴性乳腺癌相对特异性,AGR2在三阴性乳腺癌肿瘤免疫微环境中CD8+T细胞数量呈显著正相关(P<0.01),而S100B基因的表达水平与肿瘤微环境免疫细胞B细胞数量呈显著正相关(P<0.05),且AGR2表达水平与免疫检查点PDCD1显著相关(P<0.05)。结论AGR2在三阴性乳腺癌中显著低表达,其可能是三阴性乳腺癌特异性潜在的预后相关免疫标志物。

Objective Breast cancer is the most common malignant tumor in women with the highest incidence in China,and triple-negative breast cancer has the worst prognosis and its clinical treatment is challenging.This study aimed to analyze gene expression data in triple-negative breast cancer to identify potential markers for immune-related prognosis-related triple-negative breast cancer.Methods In this study,differentially expressed genes and their functions were screened by analyzing the gene expression data of triple-negative breast cancer and adjacent normal tissues in the TCGA database,and their significance for survival and prognosis was evaluated.The differentially expressed genes with prognostic significance were further analyzed by GEPIA2 database for their specificity in molecular typing of breast cancer.The immunological significance of triple-negative breast cancer-specific genes with prognostic relevance was analyzed.Results A total of 972 differentially expressed genes in triple-negative breast cancer were obtained,of which 27 were differentially expressed genes with prognostic significance,of which the significantly down-regulated gene AGR2(Anterior gradient 2)and the significantly up-regulated gene S100B(S100 calcium binding protein B)were relatively specific for triple-negative breast cancer.The number of CD8+T cells in the tumor immune microenvironment of negative breast cancer was significantly positively correlated(P<0.01),while the expression level of S100B gene was significantly positively correlated with the number of immune cells B cells in the tumor microenvironment(P<0.05),and the expression level of AGR2 was significantly correlated with the immune checkpoint PDCD1(P<0.05).Conclusion AGR2 is significantly down-expressed in triple-negative breast cancer,which may serve as a potential prognosis-related immune marker specific for triple-negative breast cancer.