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Open AccessArticle

Genotype-Based Gene Expression in Colon Tissue—Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients

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Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
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Institute of Medical Biometry and Informatics, Medical Faculty, Heidelberg University, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany
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Division of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69121 Heidelberg, Germany
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Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69121 Heidelberg, Germany
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Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69121 Heidelberg, Germany
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Division of Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
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NCT Tissue Bank, National Center for Tumor Diseases (NCT) and University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
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Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
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Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany
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Huntsman Cancer Institute, 2000 Cir of Hope Dr 1950, Salt Lake City, UT 84112, USA
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Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA
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Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf (UKE), Martinstraße 52, 20246 Hamburg, Germany
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German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 8150; https://doi.org/10.3390/ijms21218150
Received: 30 September 2020 / Revised: 26 October 2020 / Accepted: 27 October 2020 / Published: 31 October 2020
(This article belongs to the Special Issue Molecular Biomarkers in Colorectal Adenocarcinoma)
Colorectal cancer (CRC) survival has environmental and inherited components. The expression of specific genes can be inferred based on individual genotypes—so called expression quantitative trait loci. In this study, we used the PrediXcan method to predict gene expression in normal colon tissue using individual genotype data from 91 CRC patients and examined the correlation ρ between predicted and measured gene expression levels. Out of 5434 predicted genes, 58% showed a negative ρ value and only 16% presented a ρ higher than 0.10. We subsequently investigated the association between genotype-based gene expression in colon tissue for genes with ρ > 0.10 and survival of 4436 CRC patients. We identified an inverse association between the predicted expression of ARID3B and CRC-specific survival for patients with a body mass index greater than or equal to 30 kg/m2 (HR (hazard ratio) = 0.66 for an expression higher vs. lower than the median, p = 0.005). This association was validated using genotype and clinical data from the UK Biobank (HR = 0.74, p = 0.04). In addition to the identification of ARID3B expression in normal colon tissue as a candidate prognostic biomarker for obese CRC patients, our study illustrates the challenges of genotype-based prediction of gene expression, and the advantage of reassessing the prediction accuracy in a subset of the study population using measured gene expression data. View Full-Text
Keywords: genotype-based gene expression; PrediXcan; colorectal cancer; survival genotype-based gene expression; PrediXcan; colorectal cancer; survival
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MDPI and ACS Style

Deutelmoser, H.; Lorenzo Bermejo, J.; Benner, A.; Weigl, K.; Park, H.A.; Haffa, M.; Herpel, E.; Schneider, M.; Ulrich, C.M.; Hoffmeister, M.; Chang-Claude, J.; Brenner, H.; Scherer, D. Genotype-Based Gene Expression in Colon Tissue—Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients. Int. J. Mol. Sci. 2020, 21, 8150. https://doi.org/10.3390/ijms21218150

AMA Style

Deutelmoser H, Lorenzo Bermejo J, Benner A, Weigl K, Park HA, Haffa M, Herpel E, Schneider M, Ulrich CM, Hoffmeister M, Chang-Claude J, Brenner H, Scherer D. Genotype-Based Gene Expression in Colon Tissue—Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients. International Journal of Molecular Sciences. 2020; 21(21):8150. https://doi.org/10.3390/ijms21218150

Chicago/Turabian Style

Deutelmoser, Heike; Lorenzo Bermejo, Justo; Benner, Axel; Weigl, Korbinian; Park, Hanla A.; Haffa, Mariam; Herpel, Esther; Schneider, Martin; Ulrich, Cornelia M.; Hoffmeister, Michael; Chang-Claude, Jenny; Brenner, Hermann; Scherer, Dominique. 2020. "Genotype-Based Gene Expression in Colon Tissue—Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients" Int. J. Mol. Sci. 21, no. 21: 8150. https://doi.org/10.3390/ijms21218150

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