他莫昔芬耐药乳腺癌的预后及肿瘤免疫浸润细胞特征
Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers.
作者信息
Cao Zhenyu, Jin Ziwei, Zeng Liyun, He Hongye, Chen Qitong, Zou Qiongyan, Ouyang Dengjie, Luo Na, Zhang Yulong, Yuan Yunchang, Yi Wenjun
机构信息
Department of General Surgery, the Second Xiangya Hospital of Central South University, Changsha, China.
Department of Glandular Surgery, Baise People's Hospital, Baise, China.
出版信息
Gland Surg. 2021 Sep;10(9):2766-2779. doi: 10.21037/gs-21-566.
BACKGROUND
The cumulative risk of distant recurrence of hormone receptor-positive (HR+) breast cancer in the past 20 years has ranged from 22% to 52% after 5 years of endo-therapy. The TNM stage, histological grade, and age are important clinical factors related to recurrence, however the exact mechanism of tamoxifen resistance is still unclear.
METHODS
Differentially expressed genes (DEGs) were identified in 10 pairs of patients who had relapsed and non-relapsed after tamoxifen treatment based on matching their clinicopathological factors. After analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 10 hub genes were identified using Cytoscape software. Next, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used to verify the expression and overall survival (OS) of the 10 hub genes respectively, and GSE96058 and Kaplan-Meier Plotter website were used to further verify the OS of , and . Finally, Immune Cell Abundance Identifier (ImmuCellAI) and the TIMER database were used to estimate immune cell infiltration and the expression of prognostic genes.
RESULTS
The DEGs were mainly enriched in the inflammatory response and cytokine-receptor interaction. The expression and the survival analysis identified , and as prognostic factors, whose overexpression in HR+/human epidermal growth factor receptor 2 (HER-2) negative breast cancer possibly predicted a longer disease-free survival. The expression levels of these 3 genes are positively correlated with immune cell infiltration. Their high expression levels may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be biomarkers for tamoxifen-resistant therapy.
CONCLUSIONS
In conclusion, the high expression of , and may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.
背景
在过去20年中，激素受体阳性（HR+）乳腺癌接受内分泌治疗5年后远处复发的累积风险为22%至52%。TNM分期、组织学分级和年龄是与复发相关的重要临床因素，然而，他莫昔芬耐药的确切机制仍不清楚。
方法
基于临床病理因素匹配，在10对接受他莫昔芬治疗后复发和未复发的患者中鉴定差异表达基因（DEG）。在对基因本体（GO）术语和京都基因与基因组百科全书（KEGG）通路进行分析后，使用Cytoscape软件鉴定出10个核心基因。接下来，分别使用实时定量逆转录聚合酶链反应（qRT-PCR）和国际乳腺癌分子分类联盟（METABRIC）数据库验证这10个核心基因的表达和总生存期（OS），并使用GSE96058和Kaplan-Meier Plotter网站进一步验证其OS。最后，使用免疫细胞丰度标识符（ImmuCellAI）和TIMER数据库评估免疫细胞浸润和预后基因的表达。
结果
DEG主要富集于炎症反应和细胞因子-受体相互作用。表达和生存分析确定[此处原文缺失具体基因名称]为预后因素，其在HR+/人表皮生长因子受体2（HER-2）阴性乳腺癌中的过表达可能预示着更长的无病生存期。这3个基因的表达水平与免疫细胞浸润呈正相关。它们的高表达水平可能预示着他莫昔芬治疗后乳腺癌患者更长的无病生存期，并且可能是他莫昔芬耐药治疗的生物标志物。
结论
总之，[此处原文缺失具体基因名称]的高表达可能预示着他莫昔芬治疗后乳腺癌患者更长的无病生存期，并且可能是他莫昔芬治疗的生物标志物。
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