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基于基因分型的结肠组织基因表达-预测准确性及其与结直肠癌患者预后的关系。

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

机构信息

Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.

Institute of Medical Biometry and Informatics, Medical Faculty, Heidelberg University, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.

出版信息

Int J Mol Sci. 2020 Oct 31;21(21):8150. doi: 10.3390/ijms21218150.

Abstract

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 and CRC-specific survival for patients with a body mass index greater than or equal to 30 kg/m (HR (hazard ratio) = 0.66 for an expression higher vs. lower than the median, = 0.005). This association was validated using genotype and clinical data from the UK Biobank (HR = 0.74, = 0.04). In addition to the identification of 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.

摘要

结直肠癌(CRC)的生存既有环境因素,也有遗传因素。可以根据个体基因型推断特定基因的表达,即所谓的表达数量性状基因座。在这项研究中,我们使用 PrediXcan 方法,使用 91 名 CRC 患者的个体基因型数据预测正常结肠组织中的基因表达,并检查预测和测量的基因表达水平之间的相关性 ρ。在 5434 个预测基因中,有 58%的 ρ 值为负值,只有 16%的 ρ 值高于 0.10。随后,我们研究了 ρ 值大于 0.10 的结肠组织中基于基因型的基因表达与 4436 名 CRC 患者生存之间的关联。我们发现,对于 BMI 大于或等于 30 kg/m 的患者,预测表达与 CRC 特异性生存之间呈负相关(高表达与低表达相比,风险比(HR)= 0.66, = 0.005)。使用英国生物库的基因型和临床数据验证了该关联(HR = 0.74, = 0.04)。除了确定正常结肠组织中 表达作为肥胖 CRC 患者候选预后生物标志物外,我们的研究还说明了基于基因型预测基因表达的挑战,以及在研究人群的子集中使用测量的基因表达数据重新评估预测准确性的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a472/7662650/e636b72c04df/ijms-21-08150-g001.jpg

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