Role of the transcription factor in hepatocellular carcinoma development and lymph node metastasis.

[BACKGROUND] Lymph node metastasis (LNM) is one of the forms of hepatocellular carcinoma (HCC) dissemination, a phenomenon that is strongly correlated with an adverse prognosis. The transcription factor has been implicated in tumor progression in other malignancies, but its prognostic significance and mechanistic role in HCC LNM remain unexplored. This study aims to explore the prognostic significance and mechanistic role of the transcription factor in HCC LNM.

[METHODS] We retrospectively enrolled 387 HCC patients who underwent radical hepatectomy with lymph-node dissection between 2013 and 2021, among whom 57 were LNM-positive and the remaining 330 were negative. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier curves and compared by log-rank test; independent prognostic factors were identified with Cox proportional-hazards regression. mRNA levels in matched primary tumors and metastatic lymph nodes were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional impacts of knockdown and overexpression were assessed in HCC cell lines via proliferation, migration, and invasion assays. Changes in epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Vimentin) were examined by Western blot.

[RESULTS] LNM, microvascular invasion (MVI), and the China Liver Cancer (CNLC) stage emerged as independent predictors of both shorter RFS and OS in the matched cohort; metastatic lymph nodes exhibited a 3.8-fold increase in mRNA compared to primary tumors (P<0.001). , knockdown significantly inhibited HCC cell proliferation, migration, and invasion, whereas overexpression produced the opposite effects. At the molecular level, modulation altered EMT marker expression-specifically, overexpression reduced E-cadherin while upregulating N-cadherin and Vimentin-demonstrating that drives EMT to promote HCC cell invasiveness and metastatic potential.

[CONCLUSIONS] In summation, this study established a correlation between LNM and diminished RFS and OS among HCC patients. Moreover, it demonstrated the significant role of in HCC progression and LNM, which appears to modulate the malignant phenotype of HCC cells, encompassing enhanced proliferation, stem cell-like properties, and invasive migration through the induction of EMT. These collective findings implicate as a promising candidate for targeted therapeutic intervention in HCC.