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

Autor: Xiaomin Lou, Yang Fan, Fenli Zhou, Guixue Hou, Yanxia Liu, Fei Chen, Jin Zi, Yan Ren, Qingchuan Zhao, Siqi Liu, Bin Bai, Yuting Liang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Proteomics
Cell
neoplasms
complement system proteins
DIA
data-independent acquisition
Biology
Adenocarcinoma
Biochemistry
Analytical Chemistry
03 medical and health sciences
GSEA
gene set enrichment analysis
Stomach Neoplasms
Signet ring cell carcinoma
Cell Line
Tumor
medicine
CRP
complemental regulation protein
Humans
Molecular Biology
030304 developmental biology
Laser capture microdissection
mass spectrometry
Neoplasm Staging
0303 health sciences
Signet ring cell
Research
030302 biochemistry & molecular biology
Stomach
signet ring cell
TME
tumor microenvironment
Cancer
SRCC
signet ring cell carcinoma
Middle Aged
medicine.disease
PDAC
poorly differentiated adenocarcinoma
medicine.anatomical_structure
WMDAC
well-moderately differentiated adenocarcinoma
AC
adenocarcinoma
Proteome
DEP
differentially expressed protein
Cancer research
H&E
hematoxylin and eosin
Female
Carcinoma
Signet Ring Cell
LCM
laser capture microdissection
Zdroj: Molecular & Cellular Proteomics : MCP
ISSN: 1535-9484
1535-9476
Popis: 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.
Graphical Abstract
Highlights • LCM-DIA extracted unprecedented proteomic details of gastric in different subtypes. • Complement cascade was found to be an SRCC-specific pathway for the first time. • Gastric cell lines were evaluated based on proteomic features for the first time. • Re-analyzable DIA data collected provide rich opportunity for future research.
In Brief This study took advantages of LCM and DIA-MS, generating a data set in the context of different subtypes of gastric tumors, globally and precisely. It was discovered for the first time that the complement cascade in SRCC tumors was specifically activated compared with AC.
Databáze: OpenAIRE
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