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参与非恶性乳腺表型的管家基因在多种癌症中广泛表达,并提供肿瘤分类的新型生物标志物。

Housekeeping genes involved in non-malignant breast phenotypes are widely expressed in multiple cancers and provide novel biomarkers of tumor classification.

作者信息

Delmonico L, Obenauer J C, Stockfisch T P, Fournier M V

机构信息

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.

Rancho BioSciences, San Diego, CA, USA.

出版信息

Braz J Med Biol Res. 2021 May 17;54(7):e10388. doi: 10.1590/1414-431X2020e10388. eCollection 2021.

Abstract

Clinically relevant biomarkers are useful to determine cancer patients' prognosis and treatments. To discover new putative biomarkers, we performed in silico analysis of a 325-gene panel previously associated with breast epithelial cell biology and clinical outcomes. Sixteen public datasets of microarray samples representing 8 cancer types and a total of 3,663 patients' samples were used for the analyses. Feature selection was used to identify the best subsets of the 325 genes for each classification, and linear discriminant analysis was used to quantify the accuracy of the classifications. A subset of 102 of the 325 genes were found to be housekeeping (HK) genes, and the classifications were repeated using only the 102 HK subset. The 325-gene panel and 102 HK subset were able to distinguish colon, gastric, lung, ovarian, pancreatic, and prostate tumors and leukemia from normal adjacent tissue, and classify disease subtypes of breast and lung cancers and leukemia with 70% or higher accuracy. HK genes have been overlooked as potential biomarkers due to their relative stability. This study describes a set of HK genes as putative biomarkers applicable to multiple cancer types worth following in subsequent validation studies.

摘要

临床相关生物标志物有助于确定癌症患者的预后和治疗方案。为了发现新的潜在生物标志物,我们对先前与乳腺上皮细胞生物学和临床结果相关的325个基因组成的基因面板进行了计算机分析。分析使用了16个代表8种癌症类型的微阵列样本公共数据集,共3663例患者样本。特征选择用于识别每种分类中325个基因的最佳子集,线性判别分析用于量化分类的准确性。发现325个基因中的102个基因子集是管家(HK)基因,仅使用102个HK基因子集重复进行分类。325个基因组成的基因面板和102个HK基因子集能够将结肠、胃、肺、卵巢、胰腺和前列腺肿瘤以及白血病与相邻正常组织区分开来,并以70%或更高的准确率对乳腺癌、肺癌和白血病的疾病亚型进行分类。由于其相对稳定性,HK基因一直被忽视作为潜在的生物标志物。本研究描述了一组HK基因作为适用于多种癌症类型的潜在生物标志物,值得在后续验证研究中进一步关注。

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