Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation
Abstract Introduction The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct‐acting antivirals (DAA) or interferon (IFN) are still not fully understood. Methods S...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4571 |
| _version_ | 1818009555140870144 |
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| author | Taisuke Imamura Yukiyasu Okamura Keiichi Ohshima Katsuhiko Uesaka Teiichi Sugiura Takaaki Ito Yusuke Yamamoto Ryo Ashida Katsuhisa Ohgi Shimpei Otsuka Sumiko Ohnami Takeshi Nagashima Keiichi Hatakeyama Yuko Kakuda Takashi Sugino Kenichi Urakami Yasuto Akiyama Ken Yamaguchi |
| author_facet | Taisuke Imamura Yukiyasu Okamura Keiichi Ohshima Katsuhiko Uesaka Teiichi Sugiura Takaaki Ito Yusuke Yamamoto Ryo Ashida Katsuhisa Ohgi Shimpei Otsuka Sumiko Ohnami Takeshi Nagashima Keiichi Hatakeyama Yuko Kakuda Takashi Sugino Kenichi Urakami Yasuto Akiyama Ken Yamaguchi |
| author_sort | Taisuke Imamura |
| collection | DOAJ |
| description | Abstract Introduction The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct‐acting antivirals (DAA) or interferon (IFN) are still not fully understood. Methods Sixty‐nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole‐exome sequencing. Results Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV‐positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV‐SVR. According to the HCV treatment, 35 HCV‐SVR HCCs were classified into two groups: eight tumors with DAA (HCV‐SVR‐DAA) and 24 tumors with interferon (HCV‐SVR‐IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV‐SVR than in HCV‐positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV‐SVR samples than in HCV‐positive samples (p = 0.048). Among the patients with HCV‐SVR, the frequency of samples with TP53 mutations was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors (p = 0.030). TP53 inactivation scores in HCV‐SVR‐DAA tumors were found to be significantly enhanced in comparison to HCV‐SVR‐IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV‐SVR‐DAA tumors. HCV‐SVR‐DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV‐SVR‐IFN. Conclusion Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV‐SVR‐DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV‐positive tumors and HCV‐SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors. |
| first_indexed | 2024-04-14T05:44:19Z |
| format | Article |
| id | doaj.art-cda7410014fc4f75b329364b7e281b20 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-14T05:44:19Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-cda7410014fc4f75b329364b7e281b202022-12-22T02:09:20ZengWileyCancer Medicine2045-76342022-04-011181769178610.1002/cam4.4571Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivationTaisuke Imamura0Yukiyasu Okamura1Keiichi Ohshima2Katsuhiko Uesaka3Teiichi Sugiura4Takaaki Ito5Yusuke Yamamoto6Ryo Ashida7Katsuhisa Ohgi8Shimpei Otsuka9Sumiko Ohnami10Takeshi Nagashima11Keiichi Hatakeyama12Yuko Kakuda13Takashi Sugino14Kenichi Urakami15Yasuto Akiyama16Ken Yamaguchi17Division of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanMedical Genetics Division Shizuoka Cancer Center Research Institute Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Shizuoka JapanCancer Diagnostics Research Division Shizuoka Cancer Center Research Institute Shizuoka JapanCancer Diagnostics Research Division Shizuoka Cancer Center Research Institute Shizuoka JapanMedical Genetics Division Shizuoka Cancer Center Research Institute Shizuoka JapanDivision of Pathology Shizuoka Cancer Center Shizuoka JapanDivision of Pathology Shizuoka Cancer Center Shizuoka JapanCancer Diagnostics Research Division Shizuoka Cancer Center Research Institute Shizuoka JapanImmunotherapy Division Shizuoka Cancer Center Research Institute Shizuoka JapanShizuoka Cancer Center Hospital and Research Institute Shizuoka JapanAbstract Introduction The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct‐acting antivirals (DAA) or interferon (IFN) are still not fully understood. Methods Sixty‐nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole‐exome sequencing. Results Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV‐positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV‐SVR. According to the HCV treatment, 35 HCV‐SVR HCCs were classified into two groups: eight tumors with DAA (HCV‐SVR‐DAA) and 24 tumors with interferon (HCV‐SVR‐IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV‐SVR than in HCV‐positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV‐SVR samples than in HCV‐positive samples (p = 0.048). Among the patients with HCV‐SVR, the frequency of samples with TP53 mutations was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors (p = 0.030). TP53 inactivation scores in HCV‐SVR‐DAA tumors were found to be significantly enhanced in comparison to HCV‐SVR‐IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV‐SVR‐DAA tumors. HCV‐SVR‐DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV‐SVR‐IFN. Conclusion Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV‐SVR‐DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV‐positive tumors and HCV‐SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors.https://doi.org/10.1002/cam4.4571direct‐acting antiviral agenthepatitis C virushepatocellular carcinomainterferonsustained virological response |
| spellingShingle | Taisuke Imamura Yukiyasu Okamura Keiichi Ohshima Katsuhiko Uesaka Teiichi Sugiura Takaaki Ito Yusuke Yamamoto Ryo Ashida Katsuhisa Ohgi Shimpei Otsuka Sumiko Ohnami Takeshi Nagashima Keiichi Hatakeyama Yuko Kakuda Takashi Sugino Kenichi Urakami Yasuto Akiyama Ken Yamaguchi Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation Cancer Medicine direct‐acting antiviral agent hepatitis C virus hepatocellular carcinoma interferon sustained virological response |
| title | Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation |
| title_full | Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation |
| title_fullStr | Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation |
| title_full_unstemmed | Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation |
| title_short | Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harbors TP53 inactivation |
| title_sort | hepatocellular carcinoma after a sustained virological response by direct acting antivirals harbors tp53 inactivation |
| topic | direct‐acting antiviral agent hepatitis C virus hepatocellular carcinoma interferon sustained virological response |
| url | https://doi.org/10.1002/cam4.4571 |
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