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Comparing miRNA Signature of Colon Cancer Primary Tumors to Metastases Formed in the Liver

ABSTRACT: Genome wide miRNA expression profiling was performed using Affymetric miRNA v. 3.0 Array on 48 samples which included paired FFPE colon tuomor and metastisized liver and paired normal colon, normal liver). The data set was divided into two categories and identified by tissue source and patient demographics: Tissue (Colon, Liver), Source (Colon Tumor Liver Met, Colon Normal, Liver Normal), Sex (Male, Female), Patient Pair. microRNAs (miRs) are frequently dysregulated in colorectal cancer (CRC) and subsets are correlated with advanced tumor stage and metastasis. Despite this, the development of prognostic biomarkers that predict metastatic potential remain limited. Our study was designed to identify, validate, and elucidate underlying biology imposed by a miR signature that defines and predicts metastatic disease. Genome-wide miR expression profiling was performed on fourteen patient-matched stage IV primary CRC tumors and corresponding liver metastases using microRNA array technology. Based on these results, this miR panel was then validated and evaluated in normal colon tissue (N = 5), early stage (I & II, N = 11) and late stage (Stage III & IV, N = 14) colorectal primary tumors via qRT-PCR.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE98406 | GEO | 2017/05/02

SECONDARY ACCESSION(S): PRJNA385008

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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Comparing miRNA Signature of Colon Cancer Primary Tumors to Metastases Formed in the Liver

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