Impact of Cytokeratin 19 Expression on the Outcomes of Unresectable Hepatocellular Carcinoma Treated with Targeted Therapy and Immunotherapy: A Propensity Score Matched Analysis

Junjie Liu,1,2 Tong Yuan,1,2 Xing Lv,1,2 Guan Tan,1,2 Lin Xue,1,2 Zhiyong Huang1,2 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhiyong Huang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email [email protected]: Cytokeratin 19 (CK19) serves as a significant prognostic indicator for hepatocellular carcinoma (HCC). However, it is uncertain if CK19 expression influences the prognosis and effectiveness of treatment in patients undergoing targeted therapy and immunotherapy for unresectable HCC. This study aimed to evaluate the prognostic value of CK19 expression in this patient population.Methods: Patients with unresectable HCC who received combined targeted therapy and immunotherapy between January 2021 and December 2023 were retrospectively analyzed in this study. CK19 expression in tumor biopsy samples from patients before treatments were identified using immunohistochemistry. Propensity score matching (PSM) was conducted in a 1:2 ratio to balance baseline features between the CK19-positive and CK19-negative groups. Survival outcomes were analyzed using the Kaplan-Meier method along with the Cox regression model. Treatment response was evaluated based on mRECIST criteria.Results: A total of 247 patients were included, and 126 were selected after-PSM (43 CK19-positive, 83 CK19-negative), with balanced baseline characteristics. After PSM, the CK19-negative group had a markedly prolonged median OS compared to the CK19-positive group (42.2 months vs 15.6 months, p < 0.001), along with an extended median PFS (28.9 months vs 7.3 months, p < 0.001). The ORR was significantly higher in the CK19-negative group than in the CK19-positive group (59.0% vs 18.6%, p < 0.001), and the DCR was also superior (96.4% vs 79.1%, p = 0.005). Multivariate Cox analysis found CK19 expression as an independent factor predicting OS and PFS.Conclusion: In patients with unresectable HCC undergoing targeted therapy and immunotherapy, CK19 expression correlated with poorer survival outcomes and diminished therapeutic response. CK19 may serve as a valuable biomarker for prognosis and treatment stratification in advanced HCC, and CK19 screening may be incorporated into clinical trial stratification and clinical decision-making.Keywords: hepatocellular carcinoma, cytokeratin 19, immunotherapy, targeted therapy, prognosis, propensity score matching