Establishment and characterization of a novel HBV-integrated hepatic sarcomatoid carcinoma cell line.

Hepatic sarcomatoid carcinoma (HSC) is a rare and highly aggressive liver malignancy with an extremely poor prognosis. The lack of well-validated cellular models has severely limited mechanistic and translational research on this disease. In this study, we established and comprehensively characterized a novel HSC cell line, designated PUMC-LICA3. This cell line was derived from surgically resected tumor tissue of a 58-year-old male patient and has been continuously cultured for more than 40 passages, with a population doubling time of 51.77 h and an epithelial-like morphology. Long-read sequencing identified HBV DNA integration at chromosome 17p11.2 without detectable covalently closed circular DNA (cccDNA) or viral antigen expression, indicating a non-replicative viral status. PUMC-LICA3 exhibited 100% tumorigenicity in NOD/SCID mice. Xenograft tumors displayed immunohistochemical features consistent with sarcomatoid carcinoma, characterized by the co-expression of epithelial markers (CK and CK19) and the mesenchymal marker vimentin. E-cadherin expression was patchy, with partial loss in subsets of tumor cells, whereas N-cadherin was diffusely expressed. Notably, PUMC-LICA3 exhibited a high epithelial-mesenchymal transition (EMT) score and, among 22 hepatocellular carcinoma (HCC), clustered most closely with JHH-6 and SNU-387. Drug sensitivity assays showed that the cell line was sensitive to cisplatin, doxorubicin and sorafenib, but resistant to 5‑fluorouracil. Whole-exome sequencing (WES) analysis revealed that the cell line largely preserved the genetic characteristics of its parental tumor throughout long-term culture. In conclusion, the newly established PUMC-LICA3 cell line represents a reliable and valuable experimental model for investigating the biological characteristics and therapeutic strategies of hepatic sarcomatoid carcinoma.