Plasma Endoglin is Associated with Favorable Outcome for Pemetrexed-Based Therapy in Advanced Non-Small Cell Lung Cancer

• Published in: Cancer management and research Vol. 13; pp. 9305 - 9318
• Main Authors: Li, Che-Hsing, Ko, Jiunn-Liang, Hsiao, Yu-Ping, Tsai, Ming-Hung, Lai, Yen-Chein, Hsin, I-Lun, Kang, Yu-Ting, Sheu, Gwo-Tarng, Lin, Wea-Lung, Wu, Ming-Fang
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: biomarker; Biomarkers; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Development and progression; Dihydrofolate reductase; Disease; endoglin; Kinases; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Lymphatic system; Medical prognosis; Medical research; Medicine, Experimental; Mutation; non-squamous non-small cell lung cancer; Oncology; Original Research; Patients; Pemetrexed; pemetrexed-based therapy; Plasma; Prognosis; prognostic factor; Proteins; Taiwan; Minneapolis Minnesota; United States > US; endoglin; non-squamous non-small cell lung cancer; prognostic factor; biomarker; pemetrexed-based therapy
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S338957

Pemetrexed-based chemotherapy (Pem-C) is the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, limited tumor-associated proteins in blood are available to predict pemetrexed response and/or survival. Plasma samples from three responders and three nonresponders with stage IIIB-IV NSCLC were collected prior to Pem-C and analyzed using Proteome Profiler Human XL Oncology Array to detect 84 oncology-related proteins. The plasma concentrations of cathepsin S, endoglin (ENG), and matrix metalloproteinases 3 and 9 in 71 patients with advanced NSCLC treated with Pem-C were further measured using enzyme-linked immunosorbent assay based on the remarkable differences in the four proteins between responders and nonresponders in the array results. Pem-C responders had significantly higher ENG levels but not the other three markers than nonresponders (mean ENG level: 27.1 ± 7.4 vs 22.3 ± 6.9, < 0.01). High ENG concentration was correlated with improved progression-free survival (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.31-0.86, < 0.01) and overall survival (HR: 0.55, 95% CI: 0.32-0.94, < 0.05) in patients treated with Pem-C, and the ENG level was an independent factor in our cohort (HR: 0.54, 95% CI: 0.33-0.89, < 0.05). ENG concentration in Pem-C responders also significantly increased at the time of best response ( < 0.05). Cumulatively, this study reveals that ENG is correlated with Pem-C responsiveness in patients, which indicates the potential use of plasma ENG levels as a non-invasive biomarker for pemetrexed-based treatment in patients with non-squamous NSCLC.