Quantitative proteomic analysis of bronchoalveolar lavage fluids from patients with small cell lung cancers

Hung M Vu; Hazara Begum Mohammad; Thy N C Nguyen; Jun Hyung Lee; Yeji Do; Ji-Youn Sung; Seung Hyeun Lee; Min-Sik Kim

doi:10.1002/prca.202300011

Quantitative proteomic analysis of bronchoalveolar lavage fluids from patients with small cell lung cancers

Proteomics Clin Appl. 2023 Sep;17(5):e2300011. doi: 10.1002/prca.202300011. Epub 2023 Mar 1.

Authors

Hung M Vu¹, Hazara Begum Mohammad¹, Thy N C Nguyen¹, Jun Hyung Lee¹, Yeji Do¹, Ji-Youn Sung², Seung Hyeun Lee³, Min-Sik Kim^{1

4

5}

Affiliations

¹ Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
² Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
³ Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
⁴ New Biology Research Center, DGIST, Daegu, Republic of Korea.
⁵ Center for Cell Fate Reprogramming and Control, DGIST, Daegu, Republic of Korea.

PMID: 36807835
DOI: 10.1002/prca.202300011

Abstract

Purpose: Small cell lung cancer (SCLC) is one of the malignant cancers with aggressive progression and poor prognosis. Bronchoalveolar lavage fluid (BALF) has been arising recently as a potential source of biomarkers for lung cancers. In this study, we performed quantitative BALF proteomic analysis to identify potential biomarkers for SCLC.

Experimental design: BALF were collected from tumor-bearing lungs and non-tumor lungs of five SCLC patients. Then, BALF proteomes were prepared for a TMT-based quantitative mass spectrometry analysis. Differentially expressed proteins (DEP) were identified when considering individual variation. Potential SCLC biomarker candidates were validated by immunohistochemistry (IHC). A public database of multiple SCLC cell lines was used to evaluate the correlation of these markers with SCLC subtypes and chemo-drug responses.

Results: We identified 460 BALF proteins in SCLC patients and observed considerable individual variation among the patients. Immunohistochemical analysis and bioinformatics resulted in the identification of CNDP2 and RNPEP as potential subtype markers for ASCL1 and NEUROD1, respectively. In addition, CNDP2 was found to be positively correlated with responses to etoposide, carboplatin, and irinotecan.

Conclusions and clinical relevance: BALF is an emerging source of biomarkers, making it useful for the diagnosis and prognosis of lung cancers. We characterized the proteomes of paired BALF samples collected from tumor-bearing and non-tumor lungs of SCLC patients. Several proteins were found elevated in tumor-bearing BALF, and especially CNDP2 and RNPEP appeared to be potential indicators for ASLC1-high and NEUROD1-high subtypes of SCLC, respectively. The positive correlation of CNDP2 with chemo-drug responses would help to make decisions for treatment of SCLC patients. These putative biomarkers could be comprehensively investigated for a clinical use towards precision medicine.

Keywords: SCX StageTips; TMT labeling; bronchoalveolar lavage fluid; proteomics; small cell lung cancer.

Publication types

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

MeSH terms

Biomarkers, Tumor / metabolism
Bronchoalveolar Lavage Fluid
Humans
Lung Neoplasms* / metabolism
Proteome
Proteomics
Small Cell Lung Carcinoma* / diagnosis

Substances

Proteome
Biomarkers, Tumor