Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy
Atezolizumab/bevacizumab (Atezo/Bev) combination therapy has become a front-line therapy for advanced hepatocellular carcinoma (HCC), but approximately 20% of patients are nonresponders. We investigated circulating biomarkers to predict therapeutic outcomes. We performed simultaneous measurement of...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/4/883 |
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| author | Yuta Myojin Takahiro Kodama Ryotaro Sakamori Kazuki Maesaka Takayuki Matsumae Yoshiyuki Sawai Yasuharu Imai Kazuyoshi Ohkawa Masanori Miyazaki Satoshi Tanaka Eiji Mita Seiichi Tawara Takayuki Yakushijin Yasutoshi Nozaki Hideki Hagiwara Yuki Tahata Ryoko Yamada Hayato Hikita Tomohide Tatsumi Tetsuo Takehara |
| author_facet | Yuta Myojin Takahiro Kodama Ryotaro Sakamori Kazuki Maesaka Takayuki Matsumae Yoshiyuki Sawai Yasuharu Imai Kazuyoshi Ohkawa Masanori Miyazaki Satoshi Tanaka Eiji Mita Seiichi Tawara Takayuki Yakushijin Yasutoshi Nozaki Hideki Hagiwara Yuki Tahata Ryoko Yamada Hayato Hikita Tomohide Tatsumi Tetsuo Takehara |
| author_sort | Yuta Myojin |
| collection | DOAJ |
| description | Atezolizumab/bevacizumab (Atezo/Bev) combination therapy has become a front-line therapy for advanced hepatocellular carcinoma (HCC), but approximately 20% of patients are nonresponders. We investigated circulating biomarkers to predict therapeutic outcomes. We performed simultaneous measurement of 34 proteins using a multiplex bead-based immunoassay in baseline plasma from 34 patients who underwent Atezo/Bev therapy as first- or second-line treatment. Logistic regression analysis showed that plasma IL-6 and interferon alpha (IFNα) levels were significant predictors of non-responders (odds ratio of 13.33 and FDR <i>p</i> = 0.021 for IL-6 and IFNα). The progression-free survival (PFS) and overall survival (OS) of patients with high IL-6 levels were significantly shorter than those of patients with low IL-6 levels. Next, we measured baseline plasma IL-6 levels in 64 HCC patients who underwent Atezo/Bev therapy by ELISA. The IL-6-high group showed higher female ratio, AST levels, tumor markers, Child–Pugh score, and vascular invasion ratio. The PFS and OS of the IL-6-high group were significantly shorter than those of the IL-6-low group. Multivariate Cox proportional hazards analysis showed that IL-6 level and age were independent risk factors for disease progression (hazard ratio of 2.785 and <i>p</i> = 0.015 for IL-6, and hazard ratio 0.306 and <i>p</i> = 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy. |
| first_indexed | 2024-03-09T22:24:42Z |
| format | Article |
| id | doaj.art-085ac7faea9e4766a05930d1f1150cb2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:24:42Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-085ac7faea9e4766a05930d1f1150cb22023-11-23T19:07:54ZengMDPI AGCancers2072-66942022-02-0114488310.3390/cancers14040883Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined ImmunotherapyYuta Myojin0Takahiro Kodama1Ryotaro Sakamori2Kazuki Maesaka3Takayuki Matsumae4Yoshiyuki Sawai5Yasuharu Imai6Kazuyoshi Ohkawa7Masanori Miyazaki8Satoshi Tanaka9Eiji Mita10Seiichi Tawara11Takayuki Yakushijin12Yasutoshi Nozaki13Hideki Hagiwara14Yuki Tahata15Ryoko Yamada16Hayato Hikita17Tomohide Tatsumi18Tetsuo Takehara19Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Ikeda Municipal Hospital, Ikeda 563-0025, JapanDepartment of Gastroenterology and Hepatology, Ikeda Municipal Hospital, Ikeda 563-0025, JapanDepartment of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka 541-8567, JapanDepartment of Gastroenterology and Hepatology, Osaka Police Hospital, Osaka 543-0035, JapanDepartment of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka 540-0006, JapanDepartment of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka 540-0006, JapanDepartment of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka 558-8558, JapanDepartment of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka 558-8558, JapanDepartment of Gastroenterology and Hepatology, Kansai Rosai Hospital, Amagasaki 660-8511, JapanDepartment of Gastroenterology and Hepatology, Kansai Rosai Hospital, Amagasaki 660-8511, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanAtezolizumab/bevacizumab (Atezo/Bev) combination therapy has become a front-line therapy for advanced hepatocellular carcinoma (HCC), but approximately 20% of patients are nonresponders. We investigated circulating biomarkers to predict therapeutic outcomes. We performed simultaneous measurement of 34 proteins using a multiplex bead-based immunoassay in baseline plasma from 34 patients who underwent Atezo/Bev therapy as first- or second-line treatment. Logistic regression analysis showed that plasma IL-6 and interferon alpha (IFNα) levels were significant predictors of non-responders (odds ratio of 13.33 and FDR <i>p</i> = 0.021 for IL-6 and IFNα). The progression-free survival (PFS) and overall survival (OS) of patients with high IL-6 levels were significantly shorter than those of patients with low IL-6 levels. Next, we measured baseline plasma IL-6 levels in 64 HCC patients who underwent Atezo/Bev therapy by ELISA. The IL-6-high group showed higher female ratio, AST levels, tumor markers, Child–Pugh score, and vascular invasion ratio. The PFS and OS of the IL-6-high group were significantly shorter than those of the IL-6-low group. Multivariate Cox proportional hazards analysis showed that IL-6 level and age were independent risk factors for disease progression (hazard ratio of 2.785 and <i>p</i> = 0.015 for IL-6, and hazard ratio 0.306 and <i>p</i> = 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy.https://www.mdpi.com/2072-6694/14/4/883multiplex immunoassayimmune checkpoint inhibitoranti-VEGF antibodyanti-PD-L1 antibodyliver cancer |
| spellingShingle | Yuta Myojin Takahiro Kodama Ryotaro Sakamori Kazuki Maesaka Takayuki Matsumae Yoshiyuki Sawai Yasuharu Imai Kazuyoshi Ohkawa Masanori Miyazaki Satoshi Tanaka Eiji Mita Seiichi Tawara Takayuki Yakushijin Yasutoshi Nozaki Hideki Hagiwara Yuki Tahata Ryoko Yamada Hayato Hikita Tomohide Tatsumi Tetsuo Takehara Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy Cancers multiplex immunoassay immune checkpoint inhibitor anti-VEGF antibody anti-PD-L1 antibody liver cancer |
| title | Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy |
| title_full | Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy |
| title_fullStr | Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy |
| title_full_unstemmed | Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy |
| title_short | Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy |
| title_sort | interleukin 6 is a circulating prognostic biomarker for hepatocellular carcinoma patients treated with combined immunotherapy |
| topic | multiplex immunoassay immune checkpoint inhibitor anti-VEGF antibody anti-PD-L1 antibody liver cancer |
| url | https://www.mdpi.com/2072-6694/14/4/883 |
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