Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer.

Abstract

Ovarian cancer (OC) is a fatal gynecological tumor with high mortality and poor prognosis. Yet, its molecular mechanism is still not fully explored, and early prognostic markers are still missing. In this study, we assessed carcinogenicity and clinical significance of family with sequence similarity 83 member D (FAM83D) in ovarian cancer by integrating single-cell RNA sequencing (scRNA-seq) and a prognostic model. A 10x scRNA-seq analysis was performed on cells from normal ovary and high-grade serous ovarian cancer (HGSOC) tissue. The prognostic model was constructed by Lasso-Cox regression analysis. The biological function of FAM83D on cell growth, invasion, migration, and drug sensitivity was examined in vitro in OC cell lines. Luciferase reporter assay was performed for binding analysis between FAM83D and microRNA-138-5p (miR-138-5p). Our integrative analysis identified a subset of malignant epithelial cells (C1) with epithelial-mesenchymal transition (EMT) and potential hyperproliferation gene signature. A FAM83D+ malignant epithelial subcluster (FAM83D+ MEC) was associated with cell cycle regulation, apoptosis, DNA repair, and EMT activation. FAM83D resulted as a viable prognostic marker in a prognostic model that efficiently predict the overall survival of OC patients. FAM83D downregulation in SKOV3 and A2780 cells increased cisplatin sensitivity, reducing OC cell proliferation, migration, and invasion. MiR-138-5p was identified to regulate FAM83D's carcinogenic effect in OC cells. Our findings highlight the importance of miR-138 -5p/FAM83D/EMT signaling and may provide new insights into therapeutic strategies for OC.