The pan‐cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target

• Published in: Environmental toxicology 2023-05, Vol.38 (5), p.1100-1117
• Main Authors: Xu, Yiying, Hirachan, Suzita, Shen, Yanyan, Huang, Qidi, Bhandari, Adheesh, Xia, Erjie
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Apoptosis - genetics; Bioinformatics; biomarker; Biomarkers; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - therapy; Cancer; Cell cycle; Cell migration; Cell proliferation; Colonies; DNA damage; DNA methylation; DNA repair; Endothelial cells; Endothelial Cells - metabolism; FAM72A; Female; Humans; Immune system; immunology; Immunotherapy; Lymphocytes; Lymphocytes T; Medical prognosis; Neoplasms; Nomograms; pan‐cancer; Prognosis; prognostic; Proliferation; Regression analysis; Survival; Survival analysis
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23751

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.