Overexpression of COL10A1 in CAFs predicts poor outcome and promotes ovarian cancer progression

Background Ovarian cancer (OC) represents one of the most lethal gynecological malignancies. Cancer-associated fibroblasts (CAFs) are present in both primary and metastatic tumors and exhibit significant functional heterogeneity, adaptability and resilience. These cells are crucial for cancer progression because of their complex signaling interactions with different cell types in the tumor microenvironment. The collagen type X alpha 1 chain (COL10A1) is notably overexpressed in CAFs and is closely associated with the initiation and progression of the disease. However, the role of the COL10A1 gene in OC-associated CAFs (OC-CAFs) remains unexplored. Methods Here, we identified the differentially expressed gene COL10A1 via the integration of multiple databases, including the GEO database and the TCGA-OV dataset. We subsequently performed further bioinformatics analyses concerning COL10A1. The external datasets were ultimately analyzed, and clinical samples were collected and examined via immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT‒PCR). Results Our findings revealed that COL10A1 expression was markedly elevated in OC-CAFs and correlated with adverse clinicopathological characteristics and poorer patient prognosis. Functional enrichment analyses indicated that COL10A1 may facilitate tumorigenesis and progression by modulating several pathways associated with cellular growth, metabolism, proliferation, and survival, particularly the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and extracellular matrix (ECM)-receptor interactions. Furthermore, we observed that COL10A1 was associated with the infiltration of various immune cells and immune checkpoints. Importantly, in clinical samples, COL10A1 expression was significantly increased in OC-CAFs, which was related to unfavorable clinicopathological features and poorer patient prognosis. Conclusions Our research indicates that CAFs with elevated COL10A1 expression may enhance OC progression through the modulation of macrophage polarization. Consequently, COL10A1 serves as a novel biomarker for predicting OC prognosis and provides a promising avenue for developing therapeutic strategies targeting the tumor microenvironment.