Dataset Information

Age-Associated Proteomic Hallmarks and Potential Clinically Actionable Targets of Colorectal Cancer

ABSTRACT: Colorectal cancer (CRC) is the third most frequent cancer usually occurring in elderly persons. However, the molecular characteristics of old-onset CRC remain largely unknown. Here we performed proteomic profiling from 52 CRC tumors and their paired non-cancerous adjacent tissues and delineated the distinct molecular attributes and hallmarks of tumor progression in old-onset CRC patients over 60 years old. Then we screened out candidate proteins highly correlated with age in CRC patients through logistic regression algorithm. Besides comparative proteomic analysis of tumors and NATs revealed a catalog of age-associated proteins, including drug targets, oncogenes, transcription factors and tumor suppressors. Immunohistochemical analysis showed that the CRC patients with high NHP2 expression had lower overall survival rate and the older persons had the worse the prognosis. Cell viability and clone formation experiments revealed that knockdown of NHP2 in HT29 and SW620 cell lines inhibited cell proliferation. Collectively, this study provides a deeper understanding of cancer biology leading to old-onset CRC, and identifies potential biomarkers and therapeutic targets for old-onset CRC patients.

ORGANISM(S): Homo Sapiens

SUBMITTER: Lunzhi Dai

PROVIDER: PXD022714 | iProX | Fri Apr 16 00:00:00 BST 2021

REPOSITORIES: iProX

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Publications

Age-Associated Proteomic Signatures and Potential Clinically Actionable Targets of Colorectal Cancer.

Gong Yanqiu Y Liu Yu Y Wang Tian T Li Zhigui Z Gao Li L Chen Haining H Shu Yang Y Li Yuan Y Xu Heng H Zhou Zongguang Z Dai Lunzhi L

Molecular & cellular proteomics : MCP 20210612

The occurrence and prevalence of colorectal cancer (CRC) is closely associated with age. More than 90% of patients with CRC are diagnosed after 50 years of age. However, CRC incidence of young individuals has been increasing since 1990s, whereas the overall CRC frequency is declining. Distinct overall survival rates between young and aged patients with CRC have been established. Tremendous efforts have been made to clarify the underlying mechanisms of age-dependent clinical differences, but it s ...[more]

PMID: 34129943

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Project description:Background: The incidence of colorectal cancer (CRC) has been steadily increasing in younger individuals over the past several decades for reasons that are incompletely defined. Identifying differences in gene expression profiles, or transcriptomes, in early-onset colorectal cancer (EOCRC, < 50 years old) patients versus later-onset colorectal cancer (LOCRC, > 50 years old) patients is one approach to understanding molecular and genetic features that distinguish EOCRC. Methods: We performed RNA-sequencing (RNA-seq) to characterize the transcriptomes of patient-matched tumors and adjacent, uninvolved (normal) colonic segments from EOCRC (n=21) and LOCRC (n=22) patients. The EOCRC and LOCRC cohorts were matched for demographic and clinical characteristics. We used The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database for validation. We used a series of computational and bioinformatic tools to identify EOCRC-specific differentially expressed genes, molecular pathways, predicted cell populations, differential gene splicing events, and predicted neoantigens. Results: We identified an eight-gene signature in EOCRC comprised of ALDOB, FBXL16, IL1RN, MSLN, RAC3, SLC38A11, WBSCR27 and WNT11, from which we developed a score predictive of overall CRC patient survival. On the entire set of genes identified in normal tissues and tumors, cell type deconvolution analysis predicted a differential abundance of immune and non-immune populations in EOCRC versus LOCRC. Gene set enrichment analysis identified increased expression of splicing machinery in EOCRC. We further found differences in alternative splicing (AS) events, including one within the long non-coding RNA, HOTAIRM1. Additional analysis of AS found seven events specific to EOCRC that encode potential neoantigens. Conclusion: Our transcriptome analyses identified genetic and molecular features specific to EOCRC which may inform future screening, development of prognostic indicators, and novel drug targets.

Dataset Information

Age-Associated Proteomic Hallmarks and Potential Clinically Actionable Targets of Colorectal Cancer

Publications

Age-Associated Proteomic Signatures and Potential Clinically Actionable Targets of Colorectal Cancer.

Similar Datasets

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