Protein profiling reveals the characteristic changes of complement cascade pathway in the tissues of gastric signet ring cell carcinoma

ABSTRACT: Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared to adenocarcinomas (ACs). Lacking of systematically molecular overview to this disease made a slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumor and adjacency including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate cellular heterogeneity of the tissues. Proteome of tissues were profiled by data independent acquisition (DIA) mass spectrometry (MS). Based on the over 6 000 proteins quantified. Univariate analysis and pathway enrichment revealed that some proteins and pathways bared the differences between SRCC and ACs. Importantly, the up regulation for a majority of complement-related proteins were iconic for SRCC but not for AC. A hypothesis, based on the proteomics evidence, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, while the SRCC cells survived the complement cytotoxicity by secreting endogenous negative regulators. Moreover, an attempt was made to seek appropriate cell models for gastric SRCC, through proteomic comparison of the 15 gastric cell lines and the gastric tumors. The prediction of supervised classifier suggested none of these gastric cell lines qualified in mimicking SRCC. This study discovered that complement cascade is activated at a higher level in gastric SRCC than AC.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Gastric Epithelium

SUBMITTER: Yuting Liang  

LAB HEAD: Yan Ren

PROVIDER: PXD022405 | Pride | 2021-02-25

REPOSITORIES: Pride