Low expression of Proto-Oncogene FOS regulated by LINC00667/ LINC00921-miR-34a-5p axis correlates with poor prognosis and restrained anti-tumor immunity in human breast cancer

Abstract The activator protein 1 transcription factor family member FOS has been demonstrated to play meaningful roles in multiple pathophysiological processes as well as in cancer. However, the prognostic value of FOS and its underlying mechanisms in cancer progression have not been fully illuminated. In this study, the pan-cancer expression level of FOS was first assessed and the expression discrepancy of FOS in multiple cancer types was confirmed. Then, survival analysis for multiple cancer types demonstrated that low FOS expression significantly correlated with poor prognosis in breast cancer (BRCA). Further, the expression profile of FOS in BRCA patients with different clinicopathological features was analyzed and lower FOS expression was found to correlate with more severe BRCA features, which verified the roles of FOS in BRCA progression. Subsequently, noncoding RNA (ncRNA) in the regulation of FOS expression in BRCA was explored, and a regulatory axis LINC00667/ LINC00921-miR-34a-5p was identified. Further, the correlation between FOS and immune micro-environment of BRCA was analyzed. We found that down-regulated FOS level was remarkably associated with high tumor purity, less anti-tumor immune cells and components, and high expression of immune checkpoints. In summary, our findings unveiled that down-regulated FOS mediated by LINC00667/ LINC00921-miR-34a-5p axis correlated with restrained anti-tumor immunity, and therefore leading to poor prognosis in BRCA.