GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation
Background: Heat stress can induce programmed cell death (PCD). Pyroptosis is a gasdermin-mediated PCD. This study hypothesized that insufficient radiofrequency ablation (IRFA) induced pyroptosis in hepatocellular carcinoma (HCC) and investigated its underlying mechanism and clinical significance. M...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323001821 |
| _version_ | 1797422662379634688 |
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| author | Xuexia Liang Qiaodan Liu Shuqin Zhu Zizi Li Hui Chen Zhongzhen Su |
| author_facet | Xuexia Liang Qiaodan Liu Shuqin Zhu Zizi Li Hui Chen Zhongzhen Su |
| author_sort | Xuexia Liang |
| collection | DOAJ |
| description | Background: Heat stress can induce programmed cell death (PCD). Pyroptosis is a gasdermin-mediated PCD. This study hypothesized that insufficient radiofrequency ablation (IRFA) induced pyroptosis in hepatocellular carcinoma (HCC) and investigated its underlying mechanism and clinical significance. Methods: Thermostatic water bath was used to stimulate IRFA in vitro. Cell viability was assessed by MTT assay. IL-1β and HMGB1 were measured by ELISA assay. LDH level was measured by LDH cytotoxicity detection kit. Permeability of cell membrane was assessed by Hoechst33342/PI fluorescence staining. RNA expression was evaluated by qRT-PCR, and protein was assessed by Western Blotting or immunofluorescence or immunohistochemistry. Gene expression with clinicopathological characteristics from HCC patients treated by RFA were analyzed for associations between GSDME expression and prognosis. Results: Our study revealed that IRFA induced pyroptosis in HCCLM3 and HepG2 cells. GSDME, rather than GSDMD, was cleaved in heat stress-induced pyroptosis in HCCLM3 and HepG2 cells due to caspase-3 activation. However, GSDME overexpression promoted HCC growth in vivo and predicted poor PFS and OS in HCC patients treated by RFA. Heat stress modulated gene expression related to PD-L1 signaling and caspase inhibitors inhibited heat-induced PD-L1 expression in residual HCC after IRFA. Gsdme overexpression caused resistance to PD-L1 inhibitor in residual HCC after IRFA by increasing infiltrating of CD3+PD-1+ or CD3+CTLA-4+ exhausted T cells. Conclusions: This study indicated that GSDME could serve as a potential prognostic biomarker and help to prescribe personalized sequential immunotherapy for HCC patients receiving RFA. |
| first_indexed | 2024-03-09T07:35:39Z |
| format | Article |
| id | doaj.art-ca02c5006f8a4c86b157f0b5e6d09204 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-09T07:35:39Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-ca02c5006f8a4c86b157f0b5e6d092042023-12-03T05:40:24ZengElsevierTranslational Oncology1936-52332024-01-0139101796GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablationXuexia Liang0Qiaodan Liu1Shuqin Zhu2Zizi Li3Hui Chen4Zhongzhen Su5Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Cancer Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaDepartment of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Cancer Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaDepartment of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Department of Pathology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaDepartment of Pathology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaDepartment of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaDepartment of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Corresponding author at: Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.Background: Heat stress can induce programmed cell death (PCD). Pyroptosis is a gasdermin-mediated PCD. This study hypothesized that insufficient radiofrequency ablation (IRFA) induced pyroptosis in hepatocellular carcinoma (HCC) and investigated its underlying mechanism and clinical significance. Methods: Thermostatic water bath was used to stimulate IRFA in vitro. Cell viability was assessed by MTT assay. IL-1β and HMGB1 were measured by ELISA assay. LDH level was measured by LDH cytotoxicity detection kit. Permeability of cell membrane was assessed by Hoechst33342/PI fluorescence staining. RNA expression was evaluated by qRT-PCR, and protein was assessed by Western Blotting or immunofluorescence or immunohistochemistry. Gene expression with clinicopathological characteristics from HCC patients treated by RFA were analyzed for associations between GSDME expression and prognosis. Results: Our study revealed that IRFA induced pyroptosis in HCCLM3 and HepG2 cells. GSDME, rather than GSDMD, was cleaved in heat stress-induced pyroptosis in HCCLM3 and HepG2 cells due to caspase-3 activation. However, GSDME overexpression promoted HCC growth in vivo and predicted poor PFS and OS in HCC patients treated by RFA. Heat stress modulated gene expression related to PD-L1 signaling and caspase inhibitors inhibited heat-induced PD-L1 expression in residual HCC after IRFA. Gsdme overexpression caused resistance to PD-L1 inhibitor in residual HCC after IRFA by increasing infiltrating of CD3+PD-1+ or CD3+CTLA-4+ exhausted T cells. Conclusions: This study indicated that GSDME could serve as a potential prognostic biomarker and help to prescribe personalized sequential immunotherapy for HCC patients receiving RFA.http://www.sciencedirect.com/science/article/pii/S1936523323001821Hepatocellular carcinomaInsufficient radiofrequency ablationGSDMEExhausted T cellPD-L1 inhibitor |
| spellingShingle | Xuexia Liang Qiaodan Liu Shuqin Zhu Zizi Li Hui Chen Zhongzhen Su GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation Translational Oncology Hepatocellular carcinoma Insufficient radiofrequency ablation GSDME Exhausted T cell PD-L1 inhibitor |
| title | GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation |
| title_full | GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation |
| title_fullStr | GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation |
| title_full_unstemmed | GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation |
| title_short | GSDME has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation |
| title_sort | gsdme has prognostic and immunotherapeutic significance in residual hepatocellular carcinoma after insufficient radiofrequency ablation |
| topic | Hepatocellular carcinoma Insufficient radiofrequency ablation GSDME Exhausted T cell PD-L1 inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323001821 |
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