DataSheet2_Identification of Five Cytotoxicity-Related Genes Involved in the Progression of Triple-Negative Breast Cancer.ZIP

Background: Breast cancer is one of the deadly tumors in women, and its incidence continues to increase. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital.
Methods: 30 pairs of human breast cancer tissue and matched normal tissue were collected and RNA sequenced in our hospital. Differentially expressed genes (DEGs) were calculated with raw data by the R package “edgeR”, and functionally annotated using R package “clusterProfiler”. Tumor-infiltrating immune cells (TIICs) were estimated using a website tool TIMER 2.0. Effects of key genes on therapeutic efficacy were analyzed using RNA-seq data and drug sensitivity data from two databases: the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP).
Results: There were 2,953 DEGs between cancerous and matched normal tissue, as well as 975 DEGs between primary breast cancer and metastatic breast cancer. These genes were primarily enriched in PI3K-Akt signaling pathway, calcium signaling pathway, cAMP signaling pathway, and cell cycle. Notably, CD8+ T cell, M0 macrophage, M1 macrophage, regulatory T cell and follicular helper T cell were significantly elevated in cancerous tissue as compared with matched normal tissue. Eventually, we found five genes (GALNTL5, MLIP, HMCN2, LRRN4CL, and DUOX2) were markedly corelated with CD8+ T cell infiltration and cytotoxicity, and associated with therapeutic response.
Conclusion: We found five key genes associated with tumor progression, CD8+ T cell and therapeutic efficacy. The findings would provide potential molecular targets for the treatment of breast cancer.

背景：乳腺癌是女性致死性肿瘤之一，其发病率持续攀升。本研究依托我院乳腺癌RNA测序（RNA sequencing, RNA-seq）数据，旨在筛选新型治疗分子。
方法：本研究收集了30对人乳腺癌组织及配对正常组织，并在我院完成RNA测序。采用R包“edgeR”对原始测序数据进行差异表达基因（differentially expressed genes, DEGs）分析，通过R包“clusterProfiler”对差异基因进行功能注释。使用在线工具TIMER 2.0评估肿瘤浸润免疫细胞（tumor-infiltrating immune cells, TIICs）的浸润情况。结合癌症细胞系百科全书（Cancer Cell Line Encyclopedia, CCLE）与癌症治疗反应门户（Cancer Therapeutics Response Portal, CTRP）两个数据库的RNA测序数据及药物敏感性数据，分析关键基因对治疗疗效的影响。
结果：癌组织与配对正常组织间共筛选出2953个差异表达基因，原发性乳腺癌与转移性乳腺癌间则筛选出975个差异表达基因。上述基因主要富集于PI3K-Akt信号通路、钙信号通路、cAMP信号通路及细胞周期通路。值得注意的是，与配对正常组织相比，癌组织中CD8+ T细胞、M0型巨噬细胞、M1型巨噬细胞、调节性T细胞及滤泡辅助性T细胞的浸润水平显著升高。最终，本研究发现5个基因（GALNTL5、MLIP、HMCN2、LRRN4CL、DUOX2）与CD8+ T细胞浸润及细胞毒性显著相关，同时与治疗反应存在关联。
结论：本研究筛选出5个与肿瘤进展、CD8+ T细胞浸润及治疗疗效相关的关键基因。本研究结果可为乳腺癌治疗提供潜在的分子靶点。