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Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

ABSTRACT: We performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. 5 peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased following surgery.

ORGANISM(S): Homo Sapiens

SUBMITTER: Chen Huang

PROVIDER: PXD011352 | iProX | Wed Apr 17 00:00:00 BST 2019

REPOSITORIES: iProX

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Project description:Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

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Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients

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