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ITRAQ analysis of colorectal cancer suggests the pathway of valine, leucine and isoleucine degradation is inactivation

ABSTRACT: Colorectal cancer (CRC) is currently the third in cancer incidence worldwide and the fourth most common cause of cancer deaths. To discover the proteins related to colon cancer, a typical inflammation-related C57B/6N mouse colon carcinogenesis model was developed using azoxymethane-dextran sodium sulfate (AOM-DSS) treated for 14 weeks. iTRAQ-based proteomics study was performed using cell membrane components enriched from colonic mucosa. Tumor tissues and their adjacent normal colon tissues from colonic cancer patients were collected for differential protein detection and metabolomics studies. Totally, 74 differentially expressed proteins were identified in the AOM/DSS treated tumor samples compared with AOM/DSS treated adjacent samples, and the saline treated control. Bioinformatics analysis showed that eight downregulated proteins were enriched in the pathway of valine, leucine and isoleucine degradation. Targeted metabolomics study showed that valine, leucine and isoleucine was upregulated in tumor tissues compared with their adjacent normal tissues from colonic cancer patients. Further real-time PCR and western blot experiments showed that the signal pathway proteins of Hadh and ALDH2 were downregulated in colon patients (colon tumor tissues vs their adjacent colon tissues), as well as in AOM/DSS treated mouse model. In all, our study showed that the pathway of valine, leucine and isoleucine degradation was inactivation in colon cancer, and Hadh and ALDH2 were two potential biomarkers for colon cancer treatment.

ORGANISM(S): Mus Musculus

SUBMITTER: Lijun zhang

PROVIDER: PXD046882 | iProX | Mon Nov 13 00:00:00 GMT 2023

REPOSITORIES: iProX

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