SLC35A2在乳腺癌中的潜在预后价值分析及表达验证

An Analysis of the Potential Prognostic Value and Expression Validation of SLC35A2 in Breast Cancer

目的乳腺癌是全球女性最常见的恶性肿瘤,在我国其发病率和死亡率呈逐年上升趋势,三阴性乳腺癌约占乳腺癌的20%。本研究旨在分析乳腺癌基因表达数据,寻找与乳腺癌预后相关的潜在标志物。方法通过分析癌症基因组图谱(the cancer genome atlas,TCGA)数据库乳腺癌和正常组织基因表达数据,筛选差异表达基因及进一步筛查对乳腺癌生存预后意义最大的差异基因。通过GEPIA2(gene expression profiling interactive analysis)数据库验证差异表达基因在不同乳腺癌分子分型的相对特异性,并通过乳腺癌临床样本行免疫组化验证其表达水平。结果本研究共分析了TCGA数据库中1101例乳腺癌组织和113例乳腺正常组织基因表达数据,获得差异表达基因2401个,包括903个上调差异表达基因和1498个下调差异表达基因,其中SLC35A2基因对乳腺癌预后意义最大;乳腺癌分子分型特异性分析显示,SLC35A2的高表达与Luminal乳腺癌,特别是Luminal A乳腺癌中预后不良最相关(P<0.05)。乳腺癌临床病例验证发现,相较于配对正常组织,SLC35A2在和Luminal A、Luminal B、HER2过表达及三阴性乳腺癌中均可见显著高表达(P<0.05);且SLC35A2表达水平与Ki67%、组织学分级、是否淋巴结转移、HER2表达差异无统计学意义,而在ER/PR阳性表达中呈显著高表达。结论SLC35A2在乳腺癌不同分子分型中均呈过表达现象,其在激素受体阳性乳腺癌中预后意义最大,其可能是激素受体阳性乳腺癌特异性潜在的预后相关标志物。

Objective Breast cancer is the most common malignant umor in women with the highest incidence in China,and triple-negative breast cancer has the worst prognosis and is difficult for clinical treatments.This study aimed to analyze gene expression dataset in triple-negative breast cancer,so as to discover potential markers for immune-related prognosis-related triple-negative breast cancer.Methods Differentially expressed genes and their functions were screened by analyzing the gene expression datasets of triple-negative breast cancer and adjacent normal tissues in the TCGA database,and their significance for survival and prognosis was analyzed.The differentially expressed genes with prognostic significance were further analyzed by GEPIA2 database for their specificity for molecular typing of breast cancer.The immunological significance of triple-negative breast cancer-specific genes with prognostic relevance was evaluated.Results The expression profiles of 1101 breast cancer tissues and 113 normal breast tissues in TCGA database were analyzed,while 2401 differentially expressed genes were obtained,including 903 up-regulated differentially expressed genes and 1498 down-regulated differentially expressed genes.Among these genes,SLC35A2 showed the greatest prognostic significance for breast cancer.The molecular typing specificity analysis of breast cancer indicated that the high expression of SLC35A2 was mostly related to the poor prognosis in luminal breast cancer,especially luminal A breast cancer(P<0.05).Clinical validation of breast cancer found that SLC35A2 was significantly overexpressed in breast cancer with luminal A,luminal B,HER2 and triple-negative breast cancer(P<0.05);The expression level of SLC35A2 showed no statistical difference with Ki67%,histological grading,lymph node metastasis,and HER2 expression,but showed significantly high expression in ER/PR positive cases.Conclusion SLC35A2 is overexpressed in different molecular types of breast cancer,and has the greatest prognostic significance in hormone receptor positive breast cancer.It might serve as a specific and potential prognostic marker for hormone receptor positive breast cancer.