PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma
Abstract Sorafenib has become the only FDA‐approved first‐line therapy for advanced hepatocellular carcinoma (HCC) for more than 10 years, but there is still no validated predictive or prognostic marker. Peptidase inhibitor 16 (PI16) is a functionally unknown gene in cancer research. This study aime...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.3331 |
| _version_ | 1797839410072387584 |
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| author | Pusen Wang Zhongyi Jiang Xueni Liu Kanru Yu Chunguang Wang Hao Li Lin Zhong |
| author_facet | Pusen Wang Zhongyi Jiang Xueni Liu Kanru Yu Chunguang Wang Hao Li Lin Zhong |
| author_sort | Pusen Wang |
| collection | DOAJ |
| description | Abstract Sorafenib has become the only FDA‐approved first‐line therapy for advanced hepatocellular carcinoma (HCC) for more than 10 years, but there is still no validated predictive or prognostic marker. Peptidase inhibitor 16 (PI16) is a functionally unknown gene in cancer research. This study aimed to determine the exact function of PI16 in HCC and whether it can represent as a biomarker for sorafenib response. We found that PI16 was over expressed in HCC tissues vs paired normal tissues. PI16 knockdown sensitize HCC cells to sorafenib treatment both in vitro and in vivo, whereas ectopic PI16 expression produced the opposite effect. Mechanistically, PI16 could suppress p38 MAPK/caspase‐dependent apoptosis in this process, and p38 MAPK inhibitor reversed the sorafenib sensitive phenotype caused by PI16 inhibition. Clinically, immunohistochemistry was used to detect PI16 levels in resected patients with HCC prior to sorafenib treatment. We showed that high PI16 levels represented an independent risk factor for disease progression in patients treated with sorafenib. Patients with low PI16 showed significantly better progression free survival and overall survival after sorafenib therapy. In conclusion, PI16 attenuates response to sorafenib treatment in HCC, and may be a helpful prognostic biomarker of sorafenib treatment. |
| first_indexed | 2024-04-09T15:57:31Z |
| format | Article |
| id | doaj.art-9ecab1b3421f444aa7e97c5c4bcb3c12 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T15:57:31Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-9ecab1b3421f444aa7e97c5c4bcb3c122023-04-25T14:00:49ZengWileyCancer Medicine2045-76342020-10-019196972698310.1002/cam4.3331PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinomaPusen Wang0Zhongyi Jiang1Xueni Liu2Kanru Yu3Chunguang Wang4Hao Li5Lin Zhong6Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract Sorafenib has become the only FDA‐approved first‐line therapy for advanced hepatocellular carcinoma (HCC) for more than 10 years, but there is still no validated predictive or prognostic marker. Peptidase inhibitor 16 (PI16) is a functionally unknown gene in cancer research. This study aimed to determine the exact function of PI16 in HCC and whether it can represent as a biomarker for sorafenib response. We found that PI16 was over expressed in HCC tissues vs paired normal tissues. PI16 knockdown sensitize HCC cells to sorafenib treatment both in vitro and in vivo, whereas ectopic PI16 expression produced the opposite effect. Mechanistically, PI16 could suppress p38 MAPK/caspase‐dependent apoptosis in this process, and p38 MAPK inhibitor reversed the sorafenib sensitive phenotype caused by PI16 inhibition. Clinically, immunohistochemistry was used to detect PI16 levels in resected patients with HCC prior to sorafenib treatment. We showed that high PI16 levels represented an independent risk factor for disease progression in patients treated with sorafenib. Patients with low PI16 showed significantly better progression free survival and overall survival after sorafenib therapy. In conclusion, PI16 attenuates response to sorafenib treatment in HCC, and may be a helpful prognostic biomarker of sorafenib treatment.https://doi.org/10.1002/cam4.3331apoptosisp38 MAPKpeptidase inhibitor 16prognosissorafenib |
| spellingShingle | Pusen Wang Zhongyi Jiang Xueni Liu Kanru Yu Chunguang Wang Hao Li Lin Zhong PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma Cancer Medicine apoptosis p38 MAPK peptidase inhibitor 16 prognosis sorafenib |
| title | PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma |
| title_full | PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma |
| title_fullStr | PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma |
| title_full_unstemmed | PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma |
| title_short | PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma |
| title_sort | pi16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma |
| topic | apoptosis p38 MAPK peptidase inhibitor 16 prognosis sorafenib |
| url | https://doi.org/10.1002/cam4.3331 |
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