Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes.
We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC.
Xue, R; Chen, L; Zhang, C; Fujita, M; Li, R; Yan, S-M; Ong, CK; Liao, X; Gao, Q; Sasagawa, S; Li, Y; Wang, J; Guo, H; Huang, Q-T; Zhong, Q; Tan, J; Qi, L; Gong, W; Hong, Z; Li, M; Zhao, J; Peng, T; Lu, Y; Lim, KHT; Boot, A; Ono, A; Chayama, K; Zhang, Z; Rozen, SG; Teh, BT; Wang, XW; Nakagawa, H; Zeng, M-S; Bai, F; Zhang, N
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