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Mol Cell Proteomics. 2021;20:100068. doi: 10.1016/j.mcpro.2021.100068. Epub 2021 Mar 03.

Proteomic Profiling of Gastric Signet Ring Cell Carcinoma Tissues Reveals Characteristic Changes of the Complement Cascade Pathway.

Molecular & cellular proteomics : MCP

Yang Fan, Bin Bai, Yuting Liang, Yan Ren, Yanxia Liu, Fenli Zhou, Xiaomin Lou, Jin Zi, Guixue Hou, Fei Chen, Qingchuan Zhao, Siqi Liu

Affiliations

  1. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China; Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China.
  2. State Key Laboratory of Cancer Biology & Department of Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
  3. College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China; Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China.
  4. Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China.
  5. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China.
  6. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  7. State Key Laboratory of Cancer Biology & Department of Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China. Electronic address: [email protected].
  8. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China; Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China. Electronic address: [email protected].

PMID: 33676000 PMCID: PMC8121970 DOI: 10.1016/j.mcpro.2021.100068

Abstract

Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared with adenocarcinomas (ACs). The lack of a systematic molecular overview of this disease has led to slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumors and adjacent tissues, including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate the cellular heterogeneity of the tissues. The proteomes of tissues were profiled by data-independent acquisition (DIA) mass spectrometry (MS). Based on the over 6000 proteins quantified, univariate analysis and pathway enrichment revealed that some proteins and pathways demonstrated differences between SRCC and ACs. Importantly, the upregulation of a majority of complement-related proteins was notable for SRCC but not for ACs. A hypothesis, based on the proteomics evidence, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, and the SRCC cells survived the complement cytotoxicity by secreting endogenous negative regulators. Moreover, an attempt was made to establish appropriate cell models for gastric SRCC through proteomic comparison of the 15 gastric cell lines and gastric tumors. The predictions of a supervised classifier suggested that none of these gastric cell lines qualified to mimic SRCC. This study discovered that the complement cascade is activated at a higher level in gastric SRCC than in ACs.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: complement system proteins; mass spectrometry; neoplasms; proteomics; signet ring cell; stomach

Conflict of interest statement

Conflict of interest The authors declare no competing interests.

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