Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by data-independent acquisition mass spectrometry

Yencheng Chao; Weipeng Jiang; Xiaocen Wang; Xiaoyue Wang; Juan Song; Cuicui Chen; Jian Zhou; Qihong Huang; Jie Hu; Yuanlin Song

doi:10.1093/cei/uxac021

Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by data-independent acquisition mass spectrometry

Clin Exp Immunol. 2022 May 13;208(1):60-71. doi: 10.1093/cei/uxac021.

Authors

Yencheng Chao^{1

2}, Weipeng Jiang^{1

2}, Xiaocen Wang¹, Xiaoyue Wang¹, Juan Song¹, Cuicui Chen¹, Jian Zhou¹, Qihong Huang³, Jie Hu¹, Yuanlin Song^{1

2

4

5

6

7}

Affiliations

¹ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
² Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, China.
³ Shanghai Respiratory Research Institute, Department of Clinical Sciences, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Shanghai Respiratory Research Institute, Shanghai, China.
⁵ National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
⁶ Department of Pulmonary Medicine, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China.
⁷ Jinshan Hospital of Fudan University, Shanghai, China.

Abstract

First-line immune checkpoint inhibitors (ICIs) have greatly ameliorated outcomes in non-small cell lung cancer (NSCLC). However, approximately a quarter of patients receiving ICIs demonstrate long-term clinical benefit, and the true responders have not been fully clarified by the existing biomarkers. To discover potential biomarkers treatment-related outcomes in plasma, mass spectrometry assay for the data-independent acquisition was analyzed plasma samples collected before the anti-PD-1 treatment. From July 2019 to January 2020, 15 patients with EGFR/ALK-negative NSCLC receiving first-line anti-programmed cell death protein 1 (PD-1) inhibitors were enrolled, and six healthy individuals have collected the plasma samples as control. We explored plasma proteome profiles and conducted stratified analyses by anti-PD-1 responders and non-responders. To validate the target proteins by ELISA, we recruited 22 additional independent patients and 15 healthy individuals from April 2021 to August 2021. By identifying biomarkers to predict better efficacy, we performed differential expression analysis in 12 responders and three non-responders. Compared with healthy individuals, hierarchical cluster analysis revealed plasma proteome profiles of NSCLC were markedly changed in 170 differentially expressed proteins. Furthermore, we discovered that SAA1, SAA2, S100A8, and S100A9 were noticeably increased among non-responders than responders, which may serve as predictive biomarkers with unfavorable responses. The validated results from all samples via ELISA have confirmed this observation. Identified a set of plasma-derived protein biomarkers (SAA1, SAA2, S100A8, and S100A9) that could potentially predict the efficacy in cohorts of patients with NSCLC treated with first-line anti-PD-1 inhibitors and deserves further prospective study.

Keywords: data-independent acquisition; immunotherapy; non-small cell lung cancer; proteomics; tumor biomarkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Immunological* / therapeutic use
B7-H1 Antigen
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immunotherapy / methods
Lung Neoplasms* / drug therapy
Lung Neoplasms* / metabolism
Mass Spectrometry
Prospective Studies

Substances

B7-H1 Antigen
Antineoplastic Agents, Immunological
Biomarkers, Tumor