Gu Lijiang, Chen Yuhang, Li Xing, Mei Yibo, Zhou Jinlai, Ma Jianbin, Zhang Mengzhao, Hou Tao, He Dalin, Zeng Jin
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China.
Cancers (Basel). 2022 Jul 31;14(15):3739. doi: 10.3390/cancers14153739.
RBPs in the development and progression of BC remains unclear. Here, we elucidated the role of RBPs in predicting the survival of patients with BC. Clinical information and RNA sequencing data of the training and validation cohorts were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Survival-related differentially expressed RBPs were identified using Cox regression analyses. A total of 113 upregulated and 54 downregulated RBPs were observed, with six showing prognostic values (AHNAK, MAP1B, LAMA2, P4HB, FASN, and GSDMB). In both the GSE32548 and GSE31684 datasets, patients with low-risk scores in survival-related six RBPs-based prognostic model showed longer overall survival than those with high-risk scores. AHNAK, MAP1B, P4HB, and FASN expression were significantly upregulated in both BC tissues and cell lines. BC tissues from high-risk group showed higher proportions of naive CD4+ T cells, M0 and M2 macrophages, and neutrophils and lower proportions of plasma cells, CD8+ T cells, and T-cell follicular helper compared to low-risk group. AHNAK knockdown significantly inhibited the proliferation, invasion, and migration of BC cells in vitro and inhibited the growth of subcutaneous tumors in vivo. We thus developed and functionally validated a novel six RBPs-based prognostic model for BC.
RBPs在乳腺癌发生发展中的作用仍不清楚。在此,我们阐明了RBPs在预测乳腺癌患者生存中的作用。分别从癌症基因组图谱和基因表达综合数据库下载了训练和验证队列的临床信息和RNA测序数据。使用Cox回归分析确定与生存相关的差异表达RBPs。共观察到113个上调的RBPs和54个下调的RBPs,其中6个显示出预后价值(AHNAK、MAP1B、LAMA2、P4HB、FASN和GSDMB)。在GSE32548和GSE31684数据集中,基于与生存相关的6个RBPs的预后模型中低风险评分的患者总生存期长于高风险评分的患者。AHNAK、MAP1B、P4HB和FASN在乳腺癌组织和细胞系中的表达均显著上调。与低风险组相比,高风险组的乳腺癌组织中幼稚CD4+T细胞、M0和M2巨噬细胞以及中性粒细胞的比例更高,而浆细胞、CD8+T细胞和滤泡辅助性T细胞的比例更低。AHNAK基因敲低显著抑制了乳腺癌细胞在体外的增殖、侵袭和迁移,并在体内抑制了皮下肿瘤的生长。因此,我们开发并在功能上验证了一种新的基于6个RBPs的乳腺癌预后模型。