Proteomic characteristics of lung adenocarcinoma tumors that are small but highly invasive

Zhenbin Qiu; Xiongwen Yang; Jin Xia; Chao Zhang; Wenfang Tang; Xiangpeng Chu; Rui Fu; Xuening Yang; Xuchao Zhang; Yilong Wu; Wenzhao Zhong

doi:10.1002/med4.38

Medicine Advances 2023, 1(4): 340-352 https://doi.org/10.1002/med4.38

Original Article |

Open Access | Issue | Published: 27 November 2023

Proteomic characteristics of lung adenocarcinoma tumors that are small but highly invasive

Show Author's Information Hide Author's Information Zhenbin Qiu^{¹^,²^,³^,}, Xiongwen Yang^{¹^,²^,³^,}, Jin Xia^{¹^,²^,³^,}, Chao Zhang^{¹^,²^,³}, Wenfang Tang^⁴, Xiangpeng Chu^{¹^,²}, Rui Fu^{¹^,²^,³}, Xuening Yang^{¹^,²}, Xuchao Zhang^{¹^,²}, Yilong Wu^{¹^,²}, Wenzhao Zhong^{¹^,²^,³}(

)

School of Medicine, South China University of Technology, Guangzhou, China

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

Department of Cardiovascular Surgery, Zhongshan People's Hospital, Zhongshan, China

Zhenbin Qiu, Xiongwen Yang and Jin Xia contributed equally.

Keywords:

metastasis, proteomics, focal adhesion, lung adenocarcinoma, lymph node

Cite this article:

Qiu Z, Yang X, Xia J, et al. Proteomic characteristics of lung adenocarcinoma tumors that are small but highly invasive. Medicine Advances, 2023, 1(4): 340-352. https://doi.org/10.1002/med4.38

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Abstract Full text Electronic supplementary material About this article

Abstract

Background

Understanding the molecular mechanism of early lymph node metastasis among lung adenocarcinoma (LUAD) is essential for developing novel therapeutic agents. Proteomic studies helped generate molecular landscape for LUAD. However, the molecular basis of early lymph node metastases remains unknown in patients with LUAD.

Methods

Surgically resected LUAD tissues and paired normal tissues were selected from 25 patients with stage pT1bN2M0 (group of metastases [GM]) and 27 patients with stage T2b‐3N0M0 (group of large primary focus, GL) who had not undergone any anti‐tumor treatment. 4D‐Label‐free proteomics sequencing was performed among these tissues. The clinicopathological information was retrieved from the electronic medical record system in Guangdong Provincial People's Hospital.

Results

Compared with GL tumor tissue, 89 upregulated and 155 downregulated proteins were identified in GM tumor tissue. Upregulated proteins of GM were enriched in the ECM‐receptor interaction and PI3K‐AKT pathway under Kyoto Encyclopedia of Genes and Genomes enrichment analysis. And then, the median disease‐free survival (DFS) of GM phenotype patients was used as the cut‐off value, and GM was divided into two groups with significantly different survival outcomes (DFS good vs. DFS Poor: DFS: p < 0.0001; overall survival: p = 0.0017). All members of the Microchromosome maintenance protein family were highly expressed in the DFS‐poor group, especially MCM2. Proteome‐based stratification of LUAD revealed three subtypes (S‐2, S‐2, and S‐3) related to different clinical and molecular features. S‐3 had higher catabolism‐related pathways enriched, such as amino sugar and nucleotide sugar metabolism and fructose and mannose metabolism, which has the worst prognosis (S1 vs. S2 vs. S3, RFS: p = 0.042).

Conclusions

Proteomics analyses revealed that the activation of the extracellular matrix and intracellular signal transduction might be the driving mechanisms for early lymph node metastasis. Higher expressed cell proliferation related pathways of early lymph node metastatic LUAD may accelerate the recurrence after curative surgery. Three proteomic subgroups of LUAD with distinct molecular and clinical characteristics were identified, the one of which characterized by enrichment of catabolism‐related pathways displayed the worst survival data.

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About this article

Proteomic characteristics of lung adenocarcinoma tumors that are small but highly invasive

Show Author's information Hide Author's Information Zhenbin Qiu^{¹^,²^,³^,}, Xiongwen Yang^{¹^,²^,³^,}, Jin Xia^{¹^,²^,³^,}, Chao Zhang^{¹^,²^,³}, Wenfang Tang^⁴, Xiangpeng Chu^{¹^,²}, Rui Fu^{¹^,²^,³}, Xuening Yang^{¹^,²}, Xuchao Zhang^{¹^,²}, Yilong Wu^{¹^,²}, Wenzhao Zhong^{¹^,²^,³}(

)

School of Medicine, South China University of Technology, Guangzhou, China

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

Department of Cardiovascular Surgery, Zhongshan People's Hospital, Zhongshan, China

Zhenbin Qiu, Xiongwen Yang and Jin Xia contributed equally.

Abstract

Background

Methods

Results

Conclusions

Keywords: metastasis, proteomics, focal adhesion, lung adenocarcinoma, lymph node

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Received: 11 May 2023

Accepted: 09 September 2023

Published: 27 November 2023

Issue date: December 2023

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This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.