PMID- 32366840 OWN - NLM STAT- MEDLINE DCOM- 20210312 LR - 20210504 IS - 2041-4889 (Electronic) VI - 11 IP - 5 DP - 2020 May 4 TI - Oncogenic driver genes and tumor microenvironment determine the type of liver cancer. PG - 313 LID - 10.1038/s41419-020-2509-x [doi] LID - 313 AB - Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor microenvironment, such as inflammatory microenvironments caused by viral hepatitis, alcoholic or nonalcoholic steatohepatitis, carbon tetrachloride (CCl(4)), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and necroptosis-associated hepatic cytokine microenvironment caused by necroptosis of hepatocytes. However, the impact of different types of microenvironments on the phenotypes of PLC generated by distinct oncogenes is still unclear. In addition, the cell origin of different liver cancers have not been clarified, as far as we know. Recent researches show that mature hepatocytes retain phenotypic plasticity to differentiate into cholangiocytes. More importantly, our results initially demonstrated that HCC, ICC, and cHCC-ICC could originate from mature hepatocytes rather than liver progenitor cells (LPCs), hepatic stellate cells (HSCs) and cholangiocytes in AKT-driven, AKT/NICD-driven and AKT/CAT-driven mouse PLC models respectively by using hydrodynamic transfection methodology. Therefore, liver tumors originated from mature hepatocytes embody a wide spectrum of phenotypes from HCC to CC, possibly including cHCC-ICC and HB. However, the underlying mechanism determining the cancer phenotype of liver tumors has yet to be delineated. In this review, we will provide a summary of the possible mechanisms for directing the cancer phenotype of liver tumors (i.e., ICC, HCC, and cHCC-ICC) in terms of oncogenic driver genes and tumor microenvironment. Moreover, this study initially revealed the cell origin of different types of liver cancer. FAU - Wang, Gang AU - Wang G AD - Department of General Surgery, The 74th Group Army Hospital, Guangzhou, 510220, China. AD - Department of General Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710032, Shaanxi, China. FAU - Wang, Qian AU - Wang Q AD - Department of General Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710032, Shaanxi, China. AD - Department of Anorectal Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China. FAU - Liang, Ning AU - Liang N AUID- ORCID: 0000-0003-4201-9220 AD - Department of General Surgery, The 75th Group Army Hospital, Dali, 671000, China. FAU - Xue, Hongyuan AU - Xue H AD - Department of General Surgery, Huashan North Hospital, Fudan University, Shanghai, 201907, China. FAU - Yang, Tao AU - Yang T AD - Department of Pain Treatment, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710032, Shanxi, China. FAU - Chen, Xuguang AU - Chen X AD - Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, 510091, China. FAU - Qiu, Zhaoyan AU - Qiu Z AD - Department of General Surgery, Chinese PLA General Hospital, Beijing, China. FAU - Zeng, Chao AU - Zeng C AD - Department of Cardiology, The 74th Group Army Hospital, Guangzhou, 510318, China. FAU - Sun, Tao AU - Sun T AD - Departmentof Neurosurgery, First Affiliated Hospital, Zhengzhou University, Zheng zhou, 450052, China. FAU - Yuan, Weitang AU - Yuan W AD - Department of Anorectal Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China. FAU - Liu, Chaoxu AU - Liu C AD - Department of General Surgery, Huashan North Hospital, Fudan University, Shanghai, 201907, China. chaoxuliu@yahoo.com. AD - Department of Anorectal Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, 310003, China. chaoxuliu@yahoo.com. FAU - Chen, Zhangqian AU - Chen Z AD - Department of Infectious Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an, 710032, Shaanxi, China. Chenzq1@fmmu.edu.cn. AD - State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi'an, 710032, Shaanxi, China. Chenzq1@fmmu.edu.cn. FAU - He, Xianli AU - He X AD - Department of General Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710032, Shaanxi, China. hexianli999@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200504 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 SB - IM MH - Bile Duct Neoplasms/genetics/pathology MH - Cholangiocarcinoma/genetics/pathology MH - Hepatocytes/pathology MH - Humans MH - Liver Neoplasms/*genetics/*pathology MH - *Oncogenes MH - Signal Transduction/genetics MH - Tumor Microenvironment/*genetics PMC - PMC7198508 COIS- The authors declare that they have no conflict of interest. EDAT- 2020/05/06 06:00 MHDA- 2021/03/13 06:00 PMCR- 2020/05/04 CRDT- 2020/05/06 06:00 PHST- 2020/02/17 00:00 [received] PHST- 2020/04/14 00:00 [accepted] PHST- 2020/04/10 00:00 [revised] PHST- 2020/05/06 06:00 [entrez] PHST- 2020/05/06 06:00 [pubmed] PHST- 2021/03/13 06:00 [medline] PHST- 2020/05/04 00:00 [pmc-release] AID - 10.1038/s41419-020-2509-x [pii] AID - 2509 [pii] AID - 10.1038/s41419-020-2509-x [doi] PST - epublish SO - Cell Death Dis. 2020 May 4;11(5):313. doi: 10.1038/s41419-020-2509-x.