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Apelin, a novel predictive biomarker for bevacizumab response in colorectal cancer

ABSTRACT: Gene expression profiles of various isolated normal and tumour cell types The goal was to identify genes differentially expressed in different cell types between normal and tumour tissues. To this end, different cell types (endothelial cells, macrophages and epithelial cells) were isolated from non-paired primary normal colon tissues and colorectal carcinomas and subsequently RNA was isolated. Endothelial cells and epithelial cells were isolated using facs-sorting, whereas macrophages were isolated by means of plastic adherence. For comparison RNA was also isolated from non-paired whole normal colon tissue and whole tumour colorectal carcinomas (so called “bulk”). RNA was processed and hybridized onto Agilent microarrays. Primary goal was to establish an endothelial cell genetic profile. For this we compared the gene expression of tumour endothelial cells (TECs) with normal endothelial cells (NECs).

ORGANISM(S): Homo sapiens

PROVIDER: GSE89287 | GEO | 2016/10/29

SECONDARY ACCESSION(S): PRJNA351247

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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Apelin, a novel predictive biomarker for bevacizumab response in colorectal cancer

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