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Comparative study of gene expression in human colorectal cancer tissues and normal mucosa

ABSTRACT: The purpose of our study was to better understand the genetic mechanism of oncogenesis for human colorectal cancer and to identify potential new tumour markers of use in clinical practice. Results: Comparing cancerous tissues with normal colonic mucosa we identified 584 known genes (3%) differentially expressed to a significant degree (p<0.001). Many of the transcripts that were more abundant in tumours than in non-neoplastic tissues appear to reflect important events for colon carcinogenesis. For example, a significant number of these genes serve as apoptotic inhibitors (e.g. BFAR, BIRC1, BIRC6). Furthermore, we observed the simultaneous upregulation of HLA-E and the downregulation of b2-microglobulin; these genes strongly support a potential tumour escape strategy from immune surveillance in colon cancer tissues. Conclusions: Our study provides new gene candidates in the pathogenesis of human CRC disease. From our results we hypothesise that CRC cells escape immune surveillance through a specific gene expression alteration; moreover, overexpression of several survival genes seems to confer a more anti-apoptotic phenotype. These genes are involved in pathways not previously implicated in CRC pathogenesis and they may provide new targets for therapy. Keywords: disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE3294 | GEO | 2006/03/01

SECONDARY ACCESSION(S): PRJNA92801

REPOSITORIES: GEO

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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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Comparative study of gene expression in human colorectal cancer tissues and normal mucosa

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