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

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

Minwei Bao #  1 , Yuxia Huang #  2 , Zhongping Lang #  3 , Hui Zhao  2   4 , Yuichi Saito  5   6 , Tatsuya Nagano  7 , Izumi Kawagoe  8 , Duilio Divisi  9 , Xiaoyi Hu  2 , Gening Jiang  1
Affiliations

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

Minwei Bao et al. Transl Lung Cancer Res. 2022 Jul.

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.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-467/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The flowchart of the study. NSCLC, non-small cell lung cancer.
Figure 2
Figure 2
The overlapping proteins among the top 20 proteins and the dataset by Kuang et al. (24). APOA1, apolipoprotein A-I; FGA, fibrinogen alpha chain; APOE, apolipoprotein E; FGG, fibrinogen gamma chain; FGB, fibrinogen beta chain; C4BPA, c4b-binding protein alpha chain; ALB, albumin.
Figure 3
Figure 3
GO and KEGG analysis of the top 20 proteins in plasma-derived exosomes in NSCLC patients. (A) GO analysis of the top 20 expressed proteins in plasma-derived exosomes in NSCLC patients. (B) KEGG analysis of the top 20 expressed proteins in plasma-derived exosomes in NSCLC patients. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; NSCLC, non-small cell lung cancer.
Figure 4
Figure 4
GO and KEGG analysis of the top 20 proteins in plasma-derived exosomes in lung squamous cell carcinoma patients. (A) GO analysis of the top 20 expressed proteins in plasma-derived exosomes in lung squamous cell carcinoma patients. (B) KEGG analysis of the top 20 expressed proteins in plasma-derived exosomes in lung squamous cell carcinoma patients. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 5
Figure 5
GO and KEGG analysis of the top 20 proteins in plasma-derived exosomes in lung adenocarcinoma patients. (A) GO analysis of the top 20 expressed proteins in plasma-derived exosomes in lung adenocarcinoma patients. (B) KEGG analysis of the top 20 expressed proteins in plasma-derived exosomes in lung adenocarcinoma patients. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 6
Figure 6
GO and KEGG analysis of the overlapping exosome proteins. (A) GO analysis of the 7 overlapping exosome proteins between this study and the report by Kuang et al. (B) KEGG analysis of the 7 overlapping exosome proteins. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 7
Figure 7
The differentially expressed proteins in the plasma-derived exosomes between lung squamous cell carcinoma and lung adenocarcinoma.
Figure 8
Figure 8
The factors distinguishing lung squamous cell carcinoma from lung adenocarcinoma. (A) Univariate analysis and multivariate logistic regression models. (B) The ROC curve demonstrating the ability of MFGE8 to predict lung squamous cell carcinoma and lung adenocarcinoma. ROC, receiver operating characteristic; OR, odds ratio; CI, confidence interval; AUC, area under the curve; TNM, tumor-node-metastasis.
Figure 9
Figure 9
The relationship between differentially expressed proteins and different TNM stages. (A-L) Differentially expressed proteins in plasma exosomes from lung cancer patients with different TNM stages. (M) The correlation between the 12 differentially expressed proteins and TNM stages. TNM, tumor, node, metastasis.
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