Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of General Surgery, Breast and Thyroid Unit, Tribhuvan University Teaching Hospital, Kathmandu, Nepal.
Environ Toxicol. 2023 May;38(5):1100-1117. doi: 10.1002/tox.23751. Epub 2023 Feb 9.
In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.
在这项研究中,我们首先综合运用生物信息学技术,全面研究 FAM72A 的表达谱、突变状态和生存分析,以及 FAM72A 与 DNA 损伤修复、甲基化和细胞干性分析的相关性。此外,我们还分析了 FAM72A 与免疫细胞浸润和通路富集的关系。FAM72A 在乳腺癌 (BC) 中的作用非常显著,因此我们分析了 FAM72A 在 BC 中的预后意义和临床病理参数相关性。我们还通过体外实验验证了生物学功能。FAM72A 在 26 种总共 31 种癌症中高表达,而在仅 5 种癌症中低表达。FAM72A 的表达与 9 种癌症的临床分期相关,在 31 种癌症中无病生存率有显著差异。此外,FAM72A 在 BC 中与癌症相关成纤维细胞和内皮细胞呈负相关,但与滤泡辅助 T 细胞呈正相关。单因素和多因素 cox 回归分析确定 T、N、M、年龄和 FAM72A 表达是影响 BC 预后的独立因素,因此我们创建了一个列线图来预测患者的生存获益。在体外实验中,我们验证了下调 FAM72A 不仅抑制了乳腺癌细胞的增殖、集落形成、细胞迁移、细胞侵袭和 G2/M 细胞周期转变,而且还促进了细胞凋亡。我们的研究发现 FAM72A 是一种具有临床意义的生物标志物,可用于预测预后,并为 BC 的免疫治疗提供指导靶标。