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 that has distinct features in cellular morphology, epidemiology and clinicopathology compared with adenocarcinomas (ACs). Lacking of systematically molecular overview to this disease made a slow progress in diagnosis and therapy for SRCC. In the present proteomics study, the gastric tissues were collected from tumor and adjacent regions including 14 SRCC and 34 AC cases, and laser capture microdissection (LCM) was employed to eradicate cellular heterogeneity of the tissues. Over 6,000 proteins were quantified through data independent acquisition (DIA) mass spectrometry (MS). The quantitative profiles of proteomes in tumor tissues, either AC or SRCC, were dramatically different from that in the corresponding adjacencies, whereas the SRCC proteomes appeared not distinguishable to the AC proteomes via hierarchical clustering. However, focusing on univariate analysis and pathway enrichment unrevealed that some proteins and pathways bared the differences between SRCC and ACs. Importantly, the abundance changes for a bulk of proteins involved in complement cascade were highly associated with SRCC but not so sensitive to the AC status. A hypothesis, therefore, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, while the SRCC cells survived from the complement cytotoxicity by secreting negative regulators. Moreover, an attempt was made to seek appropriate cell model for gastric SRCC, through proteomic comparison of the 15 gastric cell lines and the gastric tumors. The prediction upon supervised classifier suggested none of these gastric cell lines qualified in mimic to SRCC.