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

Che-Hsing Li; Jiunn-Liang Ko; Yu-Ping Hsiao; Ming-Hung Tsai; Yen-Chein Lai; I-Lun Hsin; Yu-Ting Kang; Gwo-Tarng Sheu; Wea-Lung Lin; Ming-Fang Wu

doi:10.2147/CMAR.S338957

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

Cancer Manag Res. 2021 Dec 22:13:9305-9318. doi: 10.2147/CMAR.S338957. eCollection 2021.

Authors

Che-Hsing Li^#^{1

2}, Jiunn-Liang Ko^#^{1

3

4}, Yu-Ping Hsiao^{5

6}, Ming-Hung Tsai⁷, Yen-Chein Lai⁸, I-Lun Hsin^{3

4}, Yu-Ting Kang^{3

4}, Gwo-Tarng Sheu^{1

3

4}, Wea-Lung Lin^{6

9}, Ming-Fang Wu^{1

4

6}

Affiliations

¹ Divisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan.
² Graduate Program in Immunology & Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.
³ Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan.
⁴ CSMU Lung Cancer Research Center, Chung Shan Medical University, Taichung, 402, Taiwan.
⁵ Division of Dermatology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan.
⁶ School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan.
⁷ Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40447, Taiwan.
⁸ Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan.
⁹ Department of Pathology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan.

^# Contributed equally.

Abstract

Purpose: 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.

Patients and methods: Plasma samples from three responders and three nonresponders with stage IIIB-IV NSCLC were collected prior to Pem-C and analyzed using Proteome Profiler^TM 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.

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, p < 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, p < 0.01) and overall survival (HR: 0.55, 95% CI: 0.32-0.94, p < 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, p < 0.05). ENG concentration in Pem-C responders also significantly increased at the time of best response (p < 0.05).

Conclusion: 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.

Keywords: biomarker; endoglin; non-squamous non-small cell lung cancer; pemetrexed-based therapy; prognostic factor.

Grants and funding

This work was supported by funding from the Ministry of Science and Technology, (Taipei, Taiwan) to Prof. Ko (MOST 108-2320-B-040 −015 -MY3) and Prof. Wu (MOST 110-2314-B-040 −029-) and from Chung Shan Medical University Hospital (Taichung, Taiwan) to Prof. Wu (CSH-2021-C-031).