Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma

Background: Epithelial cell adhesion molecule (EpCAM), a well-established marker for circulating tumor cells, plays a crucial role in the complex process of cancer metastasis. The primary objective of this investigation is to study EpCAM expression in pan-cancer and elucidate its significance in the context of kidney renal clear cell carcinoma (KIRC). Methods: Data obtained from the public database was harnessed for the comprehensive assessment of the EpCAM expression levels and prognostic and clinicopathological correlations in thirty-three types of cancer. EpCAM was validated in our own KIRC sequencing and immunohistochemical cohorts. Subsequently, an in-depth exploration was conducted to scrutinize the interrelationship between EpCAM and various facets, including immune cells, immune checkpoints, and chemotherapy drugs. We employed Cox regression analysis to identify prognostic immunomodulators associated with EpCAM, which were subsequently utilized in the development of a prognostic model. The model was validated in our own clinical cohort and public datasets, and compared with 137 published models. The role of EpCAM in KIRC was explored by biological function experiments in vitro. Results: While EpCAM exhibited pronounced overexpression across a wide spectrum of cancer types, a notable reduction was observed in KIRC tissues. As grade increased, EpCAM expression decreased. EpCAM expression decreased in patients without metastasis. EpCAM mRNA and protein levels were used as independent, favorable prognostic factors in patients with KIRC in our own cohort. The expression of EpCAM exhibited strong associations with immune-related pathways, demonstrating an inverse correlation with the majority of immune cell types. Immune checkpoint inhibitors exert better therapeutic effects on patients with low EpCAM expression. In addition, EpCAM can be used as a drug resistance indicator and guide the clinical medication of patients with KIRC. A robust model, which had good predictive accuracy and applicability, showed significant superiority over other models. Importantly, EpCAM played the dual roles of promoting proliferation and resisting metastasis in KIRC. Conclusion: In the context of KIRC, EpCAM assumes a surprising dual role, where it not only facilitates cell proliferation but also exerts resistance against the metastatic process. EpCAM serves as a standalone prognostic marker for patients with KIRC, and related models can also effectively predict prognosis. These discoveries offer novel perspectives on the functional significance of EpCAM in the context of KIRC.