CTTN overexpression on circulating tumor cells promotes hepatocellular carcinoma recurrence via enhancing the proliferation and clonality of circulating tumor cells.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality. Circulating tumor cells (CTCs) are widely recognized as the origin of hematogenous tumor metastasis. Cortactin (CTTN) plays a critical role in epithelial-mesenchymal transition, which is a critical step for malignant progression of tumor. This study aims to clarify the correlation between CTCs and recurrence in HCC. A total of 80 clinical patients were participated in this study and received 50 qualified peripheral blood samples. Patient clinical basic information was collected, CTC cells are isolated and counted at baseline to analyze the sensitivity and correlation of CTC counts as a patient recurrence biomarker. In-situ cancer mice of HCC were used to observe the effects of CTTN overexpression and knockdown on CTCs. The sensitivity and specificity of CTCs detection (>4.5/5 mL) were 90% and 82.5% (AUC = 0.871). Patients were divided into the CTC-Low group (n = 34) and CTC-High group (n = 16) at CTCs counts >4.5/5 mL. CTC >4.5/5 mL was associated with recurrence with a chi-square statistic (χ(2)) of 19.324 and p <0.001. The effect size, quantified by Cramer's V, was 0.622. CTTN is expressed on CTCs of HCC patients and CTTN overexpression promoted in-situ cancer growth and metastasis, increasing CTC numbers in HCC mice, while CTTN knockdown has the opposite effects. This study provides a research basis for the identification of clinical biomarker of CTTN for predicting the prognosis of patients with HCC after surgery and offers potential targets for the blockade therapy of CTCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00879-4.