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网络分析确定DAPK3作为淋巴侵袭和结肠腺癌预后的潜在生物标志物。

Network analysis identifies DAPK3 as a potential biomarker for lymphatic invasion and colon adenocarcinoma prognosis.

作者信息

Chen Huey-Miin, MacDonald Justin A

机构信息

Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada.

出版信息

iScience. 2021 Jul 9;24(8):102831. doi: 10.1016/j.isci.2021.102831. eCollection 2021 Aug 20.

Abstract

Colon adenocarcinoma is a prevalent malignancy with significant mortality. Hence, the identification of molecular biomarkers with prognostic significance is important for improved treatment and patient outcomes. Clinical traits and RNA-Seq of 551 patient samples in the UCSC Toil Recompute Compendium of The Cancer Genome Atlas TARGET and Genotype Tissue Expression project datasets (primary_site = colon) were used for weighted gene co-expression network analysis to reveal the association between gene networks and cancer cell invasion. One module, containing 151 genes, was significantly correlated with lymphatic invasion, a histopathological feature of higher risk colon cancer. (death-associated protein kinase 3) was identified as the pseudohub of the module. Gene ontology identified gene enrichment related to cytoskeletal organization and apoptotic signaling processes, suggesting modular involvement in tumor cell survival, migration, and epithelial-mesenchymal transformation. Although expression was reduced in patients with colon cancer, high expression of was significantly correlated with greater lymphatic invasion and poor overall survival.

摘要

结肠腺癌是一种常见的恶性肿瘤,死亡率很高。因此,识别具有预后意义的分子生物标志物对于改善治疗和患者预后非常重要。利用加州大学圣克鲁兹分校(UCSC)Toil重新计算的癌症基因组图谱(TCGA)TARGET和基因型组织表达(GTEx)项目数据集中551例患者样本的临床特征和RNA测序(primary_site = 结肠)进行加权基因共表达网络分析,以揭示基因网络与癌细胞侵袭之间的关联。一个包含151个基因的模块与淋巴侵袭显著相关,淋巴侵袭是高风险结肠癌的一种组织病理学特征。死亡相关蛋白激酶3(DAPK3)被确定为该模块的假枢纽。基因本体论确定了与细胞骨架组织和凋亡信号传导过程相关的基因富集,表明该模块参与肿瘤细胞存活、迁移和上皮-间质转化。虽然DAPK3在结肠癌患者中表达降低,但DAPK3高表达与更大的淋巴侵袭和较差的总生存期显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/8326195/6f57414ac11f/fx1.jpg

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