Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer

Minwei Bao; Yuxia Huang; Zhongping Lang; Hui Zhao; Yuichi Saito; Tatsuya Nagano; Izumi Kawagoe; Duilio Divisi; Xiaoyi Hu; Gening Jiang

doi:10.21037/tlcr-22-467

Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer

Transl Lung Cancer Res. 2022 Jul;11(7):1434-1452. doi: 10.21037/tlcr-22-467.

Authors

Minwei Bao^#¹, Yuxia Huang^#², Zhongping Lang^#³, Hui Zhao^{2

4}, Yuichi Saito^{5

6}, Tatsuya Nagano⁷, Izumi Kawagoe⁸, Duilio Divisi⁹, Xiaoyi Hu², Gening Jiang¹

Affiliations

¹ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Department of Laboratory Medicine, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, China.
⁴ Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai, China.
⁵ Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
⁶ Department of Thoracic Surgery, Saitama Cardiovascular and Respiratory Center, Saitama, Japan.
⁷ Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
⁸ Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, Tokyo, Japan.
⁹ Department of Life, Health and Environmental Sciences, University of L'Aquila, Thoracic Surgery Unit, "Giuseppe Mazzini" Hospital of Teramo, Teramo, Italy.

^# Contributed equally.

Abstract

Background: Currently, the prognosis of patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. This current study evaluated the relationship between histology of NSCLC and protein expression of exosomes in the plasma from NSCLC patients, and furthermore investigate the impact of the exosome profile on the tumor, node, metastasis (TNM) classification.

Methods: Plasma samples were collected from 26 NSCLC patients before surgery. The exosomes were extracted from the plasma and liquid chromatography-mass spectrometry (LC/MS) was used to evaluate the expression of the proteins in the exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Cytoscape 3.8.2 software. Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to identify proteins which could effectively distinguish between lung adenocarcinoma and lung squamous cell carcinoma. The relationship between protein expression and the TNM stage was calculated using Spearman rank correlation.

Results: The expression levels of ZSWIM9, FYB1, SERPINF1, C1orf68, MASP2, and IGHV3-72 were higher in patients with lung adenocarcinoma compared to patients with lung squamous cell carcinoma. MFGE8 was associated with the occurrence of squamous cell carcinoma. CORO1A was positively correlated with the TNM stage of the patients, and COL4A2 was negatively correlated with TNM stage. GO and KEGG analyses revealed that cholesterol metabolism was important in NSCLC development.

Conclusions: Lung adenocarcinoma may be distinguished from squamous cell carcinoma by the molecular profile of exosomes in the plasma samples. And, proteomics analysis suggested that cholesterol metabolism may play an important role of cancer progress in NSCLC.

Keywords: Gene Ontology (GO); Non-small cell lung cancer (NSCLC); differently expressed proteins; exosome; proteomics.