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Exploration of the typical features of tubulovillous adenoma using in-depth quantitative proteomics analysis.

ABSTRACT: This present study aimed to explore the typical protein features of tubulovillous adenoma (TVA) using proteomic and bioinformatic analyses. Tandem mass tag (TMT)-based quantitative proteomic analyses were conducted on normal mucosa, tubular adenoma, TVA and adenocarcinoma tissues. We identified 5,665 proteins categorized into seven clusters based on Pearson's correlation analysis. The bioinfomatic analysis showed mitochondrial and metabolism-related events were typical characteristics of TVA and mitochondrial-, ribosome- and matrisome-related biological processes may contribute to carcinogenesis. PLOD3 was identified as a key protein associated with the malignant potential of TVA and promoted the viability of adenoma organoids. The Cancer Genome Atlas (TCGA) analysis revealed PLOD3 as a risk factor for disease-free and overall survival. Furthermore, the PLOD3 expression correlated negatively with the abundance of B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages and myeloid dendritic cells. In conclusion, enhanced metabolic and mitochondrial reprogramming are typical features of TVA, and PLOD3 might be related to the "immune desert" phenotype and contribute to TVA tumorigenesis and colorectal cancer development.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8806592 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Exploration of the typical features of tubulovillous adenoma using in-depth quantitative proteomics analysis.

Zhang Yin Y Pan Meng M Li Chun-Yuan CY Li Jing-Ying JY Ge Wei W Xu Lai L Xiao Yi Y

Bioengineered 20211201 1

This present study aimed to explore the typical protein features of tubulovillous adenoma (TVA) using proteomic and bioinformatic analyses. Tandem mass tag (TMT)-based quantitative proteomic analyses were conducted on normal mucosa, tubular adenoma, TVA and adenocarcinoma tissues. We identified 5,665 proteins categorized into seven clusters based on Pearson's correlation analysis. The bioinfomatic analysis showed mitochondrial and metabolism-related events were typical characteristics of TVA and ...[more]

PMID: 34585630

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Project description:PurposeIn this study, we aimed to provide a comprehensive description of typical features and identify key proteins associated with the high-grade intraepithelial neoplasia- (HIN-) adenocarcinoma (AC) sequence.MethodsWe conducted tandem mass tag-based quantitative proteomic profiling of normal mucosa, HIN, and AC tissues. Protein clusters representative of the HIN-AC sequence were identified using heatmaps based on Pearson's correlation analysis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, ClueGO plugin in Cytoscape, and the Metascape database. The prognostic value of the key proteins and their effects on the tumor microenvironment and consensus molecular subtype were explored based on The Cancer Genome Atlas.ResultsWe identified 536 proteins categorized into three clusters. Among the biological processes and pathways of the highly expressed proteins in the HIN-AC sequence, proteins were predominantly enriched in response to gut microbiota, cell proliferation, leukocyte migration, and extracellular matrix (ECM) organization events. SERPINH1 and P3H1 were identified as the key proteins that promote the HIN-AC sequence. In the correlation analysis of infiltrating immune cells, both SERPINH1 and P3H1 expression correlated negatively with tumor purity, while correlating positively with abundance of CD8+ T cells, B cells, macrophage/monocytes, dendritic cells, cancer-associated fibroblasts, endothelial cells, neutrophils, and natural killer cells. Furthermore, both SERPINH1 and P3H1 expression positively correlated with common immune checkpoints and mesenchymal molecular subtype. High P3H1 expression was associated with poor disease-free survival and overall survival.ConclusionsECM-related biological processes and pathways are typical features of the HIN-AC sequence. SERPINH1 and P3H1 might be the key proteins in this sequence and be related to ECM remodeling and immune suppression status in CRC.

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Exploration of the typical features of tubulovillous adenoma using in-depth quantitative proteomics analysis.

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Exploration of the typical features of tubulovillous adenoma using in-depth quantitative proteomics analysis.

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