Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy

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Paajanen , J , Ilonen , I , Lauri , H , Järvinen , T , Sutinen , E , Ollila , H , Rouvinen , E , Lemström , K , Räsänen , J , Ritvos , O , Koli , K & Myllärniemi , M 2020 , ' Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy ' , Clinical Lung Cancer , vol. 21 , no. 3 , pp. E142-E150 . https://doi.org/10.1016/j.cllc.2019.10.013

Title: Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy
Author: Paajanen, Juuso; Ilonen, Ilkka; Lauri, Helena; Järvinen, Tommi; Sutinen, Eva; Ollila, Hely; Rouvinen, Eeva; Lemström, Karl; Räsänen, Jari; Ritvos, Olli; Koli, Katri; Myllärniemi, Marjukka
Contributor: University of Helsinki, Keuhkosairauksien yksikkö
University of Helsinki, Department of Surgery
University of Helsinki, Department of Diagnostics and Therapeutics
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, INDIVIDRUG - Individualized Drug Therapy
University of Helsinki, Department of Pathology
University of Helsinki, HUSLAB
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, Department of Physiology
University of Helsinki, Katri Koli / Principal Investigator
University of Helsinki, Department of Medicine
Date: 2020-05
Language: eng
Number of pages: 9
Belongs to series: Clinical Lung Cancer
ISSN: 1525-7304
URI: http://hdl.handle.net/10138/315743
Abstract: Activin A has previously been associated with cancer cachexia and in vitro resistance to platinum-based chemotherapy. We studied circulating activin A concentrations as well as activin B and their antagonists' follistatin/follistatin-like 3 in presurgical patients with non-small-cell lung cancer and malignant pleural mesothelioma. We found that circulating activing A levels were elevated in malignant pleural mesothelioma and associated with cancer cachexia and poor response to platinum-based chemotherapy. Circulating activing A separated non-small-cell lung cancer from benign lung lesion. Background: Previous preclinical studies have shown that activin A is overexpressed in malignant pleural mesothelioma (MPM), associates with cancer cachexia, and is observed in in vitro resistance to platinum-based chemotherapy. We evaluated circulating activin levels and their endogenous antagonists' follistatin/follistatin-like 3 in intrathoracic tumors. Materials and Methods: Patients suspected of thoracic malignancy were recruited prior to surgery. Serum samples were collected from 21 patients with MPM, 59 patients with non-small-cell lung cancer (NSCLC), and 22 patients with benign lung lesions. Circulating activin/follistatin levels were measured using enzymelinked immunosorbent assay and compared with clinicopathologic parameters. Results: Circulating activin A levels were elevated in patients with MPM when compared with patients with NSCLC or benign lung lesion samples (P <.0001). Also, follistatin and follistatin-like 3 levels were the highest in MPM, although with less difference compared with activin A. Receiver operating characteristic analysis for activin A for separating NSCLC from benign lung lesion showed an area under the curve of 0.856 (95% confidence interval, 0.77-0.94). Activin A levels were higher in patients with cachexia (P <.001). In patients with MPM, activin A levels correlated positively with computed tomographybased baseline tumor size (R = 0.549; P = .010) and the change in tumor size after chemotherapy (R = 0.743; P = .0006). Patients with partial response or stable disease had lower circulating activin A levels than the ones with progressive disease (P = .028). Conclusion: Activin A serum level could be used as a biomarker in differentiating malignant and benign lung tumors. Circulating activin A levels were elevated in MPM and associates with cancer cachexia and reduced chemotherapy response. (C) 2019 The Author(s). Published by Elsevier Inc.
Subject: 3122 Cancers
Mesothelioma
NSCLC
Biomarker
Activin A
Cancer cachexia
Chemotherapy response
SOLID TUMORS
SARCOPENIA
PROGNOSTIC VALUE
BIOMARKERS
SERUM CONCENTRATIONS
CISPLATIN
GROWTH
MYOSTATIN
FOLLISTATIN
EXPRESSION
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