Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome
Abstract Background Sarcomatoid hepatocellular carcinoma (HCC) is a rare and highly lethal histological subtype of HCC, with completely unknown genetic etiology and therapeutic targets. Methods We included 16 patients with sarcomatoid HCC receiving radical resection among 6731 cases of pathological...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4162 |
| _version_ | 1818641114205257728 |
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| author | Cheng Zhang Shi Feng Zhenhua Tu Jingqi Sun Tao Rui Xueyou Zhang Haitao Huang Qi Ling Shusen Zheng |
| author_facet | Cheng Zhang Shi Feng Zhenhua Tu Jingqi Sun Tao Rui Xueyou Zhang Haitao Huang Qi Ling Shusen Zheng |
| author_sort | Cheng Zhang |
| collection | DOAJ |
| description | Abstract Background Sarcomatoid hepatocellular carcinoma (HCC) is a rare and highly lethal histological subtype of HCC, with completely unknown genetic etiology and therapeutic targets. Methods We included 16 patients with sarcomatoid HCC receiving radical resection among 6731 cases of pathological confirmed HCC in year 2008 to 2018 in our hospital. We compared the clinical features, prognosis and cancer genome between 15 sarcomatoid HCC and propensity score‐matched 75 non‐sarcomatoid HCC patients. The other concurrent case was analyzed using phylogenetic tree to assess the tumor heterogeneity and evolution. Results Sarcomatoid HCC group showed larger tumor size, more advanced differentiation grade, lower tumor free survival (p = 0.038) and overall survival (p = 0.001), and sarcomatoid type was an independent risk factor for patient death. Integrating sarcomatoid subtype into AJCC staging could increase the diagnostic curve in predicting patient survival. The cancer genome spectrum showed sarcomatoid HCC group had significant higher mutation rates in CDKN2A, EPHA5, FANCM and MAP3K1. Mutations in CDKN2A significantly reduced tumor‐free and overall survival in sarcomatoid HCC patients. Moreover, 46.6% sarcomatoid HCC patients had druggable mutations in cell cycle pathway genes, which were targeted by Abemaciclib, et al. We also found sarcomatoid and non‐sarcomatoid lesions might originate from a common progenitor but progress differently. Conclusion Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making. |
| first_indexed | 2024-12-16T23:22:01Z |
| format | Article |
| id | doaj.art-2f743900eb4743ff9054a205bec9fc2a |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-16T23:22:01Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-2f743900eb4743ff9054a205bec9fc2a2022-12-21T22:12:08ZengWileyCancer Medicine2045-76342021-09-0110186227623810.1002/cam4.4162Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genomeCheng Zhang0Shi Feng1Zhenhua Tu2Jingqi Sun3Tao Rui4Xueyou Zhang5Haitao Huang6Qi Ling7Shusen Zheng8Department of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Pathology the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaDepartment of Surgery the First Affiliated HospitalZhejiang University School of Medicine Hangzhou ChinaAbstract Background Sarcomatoid hepatocellular carcinoma (HCC) is a rare and highly lethal histological subtype of HCC, with completely unknown genetic etiology and therapeutic targets. Methods We included 16 patients with sarcomatoid HCC receiving radical resection among 6731 cases of pathological confirmed HCC in year 2008 to 2018 in our hospital. We compared the clinical features, prognosis and cancer genome between 15 sarcomatoid HCC and propensity score‐matched 75 non‐sarcomatoid HCC patients. The other concurrent case was analyzed using phylogenetic tree to assess the tumor heterogeneity and evolution. Results Sarcomatoid HCC group showed larger tumor size, more advanced differentiation grade, lower tumor free survival (p = 0.038) and overall survival (p = 0.001), and sarcomatoid type was an independent risk factor for patient death. Integrating sarcomatoid subtype into AJCC staging could increase the diagnostic curve in predicting patient survival. The cancer genome spectrum showed sarcomatoid HCC group had significant higher mutation rates in CDKN2A, EPHA5, FANCM and MAP3K1. Mutations in CDKN2A significantly reduced tumor‐free and overall survival in sarcomatoid HCC patients. Moreover, 46.6% sarcomatoid HCC patients had druggable mutations in cell cycle pathway genes, which were targeted by Abemaciclib, et al. We also found sarcomatoid and non‐sarcomatoid lesions might originate from a common progenitor but progress differently. Conclusion Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making.https://doi.org/10.1002/cam4.4162genomesarcomatoid hepatocellular carcinomasurvivaltherapy |
| spellingShingle | Cheng Zhang Shi Feng Zhenhua Tu Jingqi Sun Tao Rui Xueyou Zhang Haitao Huang Qi Ling Shusen Zheng Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome Cancer Medicine genome sarcomatoid hepatocellular carcinoma survival therapy |
| title | Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome |
| title_full | Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome |
| title_fullStr | Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome |
| title_full_unstemmed | Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome |
| title_short | Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome |
| title_sort | sarcomatoid hepatocellular carcinoma from clinical features to cancer genome |
| topic | genome sarcomatoid hepatocellular carcinoma survival therapy |
| url | https://doi.org/10.1002/cam4.4162 |
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