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pmid:28929377
Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer.
Betul Taskoparan · Esin Gulce Seza · Secil Demirkol · Sinem Tuncer · Milan Stefek · Ali Osmay Gure · Sreeparna Banerjee
Cellular oncology (Dordrecht, Netherlands) · 2017 doi:10.1007/s13402-017-0351-7
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Complete file
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Available data indicate that, despite their similarities in structure and enzymatic functions, their roles in CRC may be divergent. Here, we aimed to determine the expression and functional implications of AKR1B1 and AKR1B10 in CRC.\nMETHODS: AKR1B1 and AKR1B10 gene expression levels were analyzed using publicly available microarray data and ex vivo CRC-derived cDNA samples. Gene Set Enrichment Analysis (GSEA), The Cancer Genome Atlas (TCGA) RNA-seq data and The Cancer Proteome Atlas (TCPA) proteome data were analyzed to determine the effect of high and low AKR1B1 and AKR1B10 expression levels in CRC patients. Proliferation, cell cycle progression, cellular motility, adhesion and inflammation were determined in CRC-derived cell lines in which these genes were either exogenously overexpressed or silenced.\nRESULTS: We found that the expression of AKR1B1 was unaltered, whereas that of AKR1B10 was decreased in primary CRCs. GSEA revealed that, while high AKR1B1 expression was associated with increased cell cycle progression, cellular motility and inflammation, high AKR1B10 expression was associated with a weak inflammatory phenotype. Functional studies carried out in CRC-derived cell lines confirmed these data. Microarray data analysis indicated that high expression levels of AKR1B1 and AKR1B10 were significantly associated with shorter and longer disease-free survival rates, respectively. A combined gene expression signature of AKR1B10 (low) and AKR1B1 (high) showed a better prognostic stratification of CRC patients independent of confounding factors.\nCONCLUSIONS: Despite their similarities, the expression levels and functions of AKR1B1 and AKR1B10 are highly divergent in CRC, and they may have prognostic implications.", "claims": [{"id": "claim-target-result", "statement": "The study used Gene Set Enrichment Analysis (GSEA) on publicly available microarray data, together with TCGA RNA-seq and TCPA proteome data, and found that AKR1B1 and AKR1B10 have divergent expression, functional effects, and prognostic implications in colorectal cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28929377", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Gene Set Enrichment Analysis (GSEA), The Cancer Genome Atlas (TCGA) RNA-seq data and The Cancer Proteome Atlas (TCPA) proteome data were analyzed to determine the effect of high and low AKR1B1 and AKR1B10 expression levels in CRC patients."}, {"asset": "source:pmid:28929377", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found that the expression of AKR1B1 was unaltered, whereas that of AKR1B10 was decreased in primary CRCs."}, {"asset": "source:pmid:28929377", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Despite their similarities, the expression levels and functions of AKR1B1 and AKR1B10 are highly divergent in CRC, and they may have prognostic implications."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study used Gene Set Enrichment Analysis (GSEA) on publicly available microarray data, together with TCGA RNA-seq and TCPA proteome data, and found that AKR1B1 and AKR1B10 have divergent expression, functional effects, and prognostic implications in colorectal cancer.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:28929377"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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