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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| Veröffentlicht in: | Cancers 2022-02, Vol.14 (4), p.883 |
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| creator | Myojin, Yuta Kodama, Takahiro Sakamori, Ryotaro Maesaka, Kazuki Matsumae, Takayuki Sawai, Yoshiyuki Imai, Yasuharu Ohkawa, Kazuyoshi Miyazaki, Masanori Tanaka, Satoshi Mita, Eiji Tawara, Seiichi Yakushijin, Takayuki Nozaki, Yasutoshi Hagiwara, Hideki Tahata, Yuki Yamada, Ryoko Hikita, Hayato Tatsumi, Tomohide Takehara, Tetsuo |
| 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
= 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
= 0.015 for IL-6, and hazard ratio 0.306 and
= 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy. |
| doi_str_mv | 10.3390/cancers14040883 |
| format | Article |
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= 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
= 0.015 for IL-6, and hazard ratio 0.306 and
= 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14040883</identifier><identifier>PMID: 35205631</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Bevacizumab ; Biomarkers ; Cancer therapies ; Chemotherapy ; Disease control ; Enzyme-linked immunosorbent assay ; Hepatocellular carcinoma ; Immunoassay ; Immunotherapy ; Interleukin 6 ; Liver cancer ; Patients ; Plasma ; Plasma proteins ; Precision medicine ; Proteins ; Regression analysis ; Risk factors ; Survival ; Survival analysis ; Tumor markers ; Tumors ; Variance analysis ; α-Interferon</subject><ispartof>Cancers, 2022-02, Vol.14 (4), p.883</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-519654541bf24e650d6668e83fca91af59cd20d978def825190f23c3b0f5f5043</citedby><cites>FETCH-LOGICAL-c421t-519654541bf24e650d6668e83fca91af59cd20d978def825190f23c3b0f5f5043</cites><orcidid>0000-0002-8361-1311 ; 0000-0002-6250-1324 ; 0000-0002-1580-607X ; 0000-0003-3950-783X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870238/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870238/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35205631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Myojin, Yuta</creatorcontrib><creatorcontrib>Kodama, Takahiro</creatorcontrib><creatorcontrib>Sakamori, Ryotaro</creatorcontrib><creatorcontrib>Maesaka, Kazuki</creatorcontrib><creatorcontrib>Matsumae, Takayuki</creatorcontrib><creatorcontrib>Sawai, Yoshiyuki</creatorcontrib><creatorcontrib>Imai, Yasuharu</creatorcontrib><creatorcontrib>Ohkawa, Kazuyoshi</creatorcontrib><creatorcontrib>Miyazaki, Masanori</creatorcontrib><creatorcontrib>Tanaka, Satoshi</creatorcontrib><creatorcontrib>Mita, Eiji</creatorcontrib><creatorcontrib>Tawara, Seiichi</creatorcontrib><creatorcontrib>Yakushijin, Takayuki</creatorcontrib><creatorcontrib>Nozaki, Yasutoshi</creatorcontrib><creatorcontrib>Hagiwara, Hideki</creatorcontrib><creatorcontrib>Tahata, Yuki</creatorcontrib><creatorcontrib>Yamada, Ryoko</creatorcontrib><creatorcontrib>Hikita, Hayato</creatorcontrib><creatorcontrib>Tatsumi, Tomohide</creatorcontrib><creatorcontrib>Takehara, Tetsuo</creatorcontrib><title>Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><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
= 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
= 0.015 for IL-6, and hazard ratio 0.306 and
= 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy.</description><subject>Bevacizumab</subject><subject>Biomarkers</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Disease control</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Hepatocellular carcinoma</subject><subject>Immunoassay</subject><subject>Immunotherapy</subject><subject>Interleukin 6</subject><subject>Liver cancer</subject><subject>Patients</subject><subject>Plasma</subject><subject>Plasma proteins</subject><subject>Precision medicine</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Risk factors</subject><subject>Survival</subject><subject>Survival analysis</subject><subject>Tumor markers</subject><subject>Tumors</subject><subject>Variance 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Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy</title><author>Myojin, Yuta ; Kodama, Takahiro ; Sakamori, Ryotaro ; Maesaka, Kazuki ; Matsumae, Takayuki ; Sawai, Yoshiyuki ; Imai, Yasuharu ; Ohkawa, Kazuyoshi ; Miyazaki, Masanori ; Tanaka, Satoshi ; Mita, Eiji ; Tawara, Seiichi ; Yakushijin, Takayuki ; Nozaki, Yasutoshi ; Hagiwara, Hideki ; Tahata, Yuki ; Yamada, Ryoko ; Hikita, Hayato ; Tatsumi, Tomohide ; Takehara, Tetsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-519654541bf24e650d6668e83fca91af59cd20d978def825190f23c3b0f5f5043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Bevacizumab</topic><topic>Biomarkers</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Disease control</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Hepatocellular carcinoma</topic><topic>Immunoassay</topic><topic>Immunotherapy</topic><topic>Interleukin 6</topic><topic>Liver cancer</topic><topic>Patients</topic><topic>Plasma</topic><topic>Plasma proteins</topic><topic>Precision medicine</topic><topic>Proteins</topic><topic>Regression analysis</topic><topic>Risk factors</topic><topic>Survival</topic><topic>Survival analysis</topic><topic>Tumor markers</topic><topic>Tumors</topic><topic>Variance analysis</topic><topic>α-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Myojin, Yuta</creatorcontrib><creatorcontrib>Kodama, Takahiro</creatorcontrib><creatorcontrib>Sakamori, Ryotaro</creatorcontrib><creatorcontrib>Maesaka, Kazuki</creatorcontrib><creatorcontrib>Matsumae, Takayuki</creatorcontrib><creatorcontrib>Sawai, Yoshiyuki</creatorcontrib><creatorcontrib>Imai, Yasuharu</creatorcontrib><creatorcontrib>Ohkawa, Kazuyoshi</creatorcontrib><creatorcontrib>Miyazaki, 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Tetsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2022-02-10</date><risdate>2022</risdate><volume>14</volume><issue>4</issue><spage>883</spage><pages>883-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>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
= 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
= 0.015 for IL-6, and hazard ratio 0.306 and
= 0.03 for age). In conclusion, circulating IL-6 levels are a novel prognostic biomarker for advanced HCC patients who undergo combined immunotherapy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35205631</pmid><doi>10.3390/cancers14040883</doi><orcidid>https://orcid.org/0000-0002-8361-1311</orcidid><orcidid>https://orcid.org/0000-0002-6250-1324</orcidid><orcidid>https://orcid.org/0000-0002-1580-607X</orcidid><orcidid>https://orcid.org/0000-0003-3950-783X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2022-02, Vol.14 (4), p.883 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8870238 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Bevacizumab Biomarkers Cancer therapies Chemotherapy Disease control Enzyme-linked immunosorbent assay Hepatocellular carcinoma Immunoassay Immunotherapy Interleukin 6 Liver cancer Patients Plasma Plasma proteins Precision medicine Proteins Regression analysis Risk factors Survival Survival analysis Tumor markers Tumors Variance analysis α-Interferon |
| title | Interleukin-6 Is a Circulating Prognostic Biomarker for Hepatocellular Carcinoma Patients Treated with Combined Immunotherapy |
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