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In-depth proteomic analysis of tissue interstitial fluid reveals biomarkers related to differentiation status in gastric adenocarcinoma

ABSTRACT: In this study, we collected an in-depth quantitative proteomic dataset of poorly and non-poorly differentiated gastric adenocarcinoma from both tissue and interstitial fluid levels and presented a comprehensive analysis from several aspects. The ISF proteome has higher abundances in proteins of blood microparticle, protein-lipid complex, immunoglobulin complex, and high-density lipoprotein particle etc. Correlation analysis of protein abundance changes between tissues and the matched ISFs uncovered consistent and inconsistent biological events.

ORGANISM(S): Homo Sapiens

SUBMITTER: Ning Ren

PROVIDER: PXD053337 | iProX | Sat Jun 22 00:00:00 BST 2024

REPOSITORIES: iProX

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Project description:TMPRSS2-ERG gene fusions that are frequently identified in prostate cancer can be generated either through chromosomal translocation or via interstitial deletion. The latter mechanism deletes an interstitial region of ~3Mb and it remains largely unanswered whether genes deleted within this region contribute to prostate cancer. By characterizing two knockin mouse models recapitulating TMPRSS2-ERG fusions with or without the interstitial deletion, we found that only those with deletion developed poorly differentiated adenocarcinomas with epithelial-to-mesenchymal transition, when under a Pten-null background. We identified several interstitial genes, including ETS2 and BACE2, whose reduced expression correlates with worse disease-free survival and lethal disease. By using an Ets2 conditional knockout allele, we demonstrated that loss of one copy of Ets2 was sufficient for prostate cancer progression when under a Pten-null background. Collectively, our data suggest that ETS2 is a prostate tumor suppressor and haploinsufficiency of one or more interstitial genes contributes to prostate cancer progression. Genotyped male mice were euthanized at 12 months of age and prostates isolated. Prostates were fixed overnight in 10% formalin and stored in 70% ethanol until tissue processing and paraffin embedding. Serial sections were cut from paraffin blocks which were stained for H&E and analyzed by a trained rodent histopathologist. Using these sections as a visual guide for specific types of lesions, the sequential sections were stained with hematoxylin and used for laser capture microdissection on ArcturusXT system. Epithelial cells within notable high grade prostate intraepithelial neoplasia (HG-PIN) lesions were microdissected from 3 mice from each corresponding genotype. In addition, poorly differentiated adenocarcinomas from PbCre;T-3Mb-Erg/+;PtenL/L mice were also dissected. RNA was isolated from the microdissected tissue using the Qiagen RNeasy FFPE kit and subjected to Nugen Amplification before microarray analysis on an Affymetrix Mouse Gene 2.0 ST chip.

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In-depth proteomic analysis of tissue interstitial fluid reveals biomarkers related to differentiation status in gastric adenocarcinoma

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