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通过加权基因共表达网络分析鉴定的黑色素瘤预后基因以及基于网络方法的药物重新定位

Prognostic genes of melanoma identified by weighted gene co-expression network analysis and drug repositioning using a network-based method.

作者信息

Wang Lu, Wei Chuan-Yuan, Xu Yuan-Yuan, Deng Xin-Yi, Wang Qiang, Ying Jiang-Hui, Zhang Si-Min, Yuan Xin, Xuan Tian-Fan, Pan Yu-Yan, Gu Jian-Ying

机构信息

Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

出版信息

Oncol Lett. 2019 Dec;18(6):6066-6078. doi: 10.3892/ol.2019.10961. Epub 2019 Oct 4.

Abstract

Melanoma is one of the most malignant types of skin cancer. However, the efficacy and utility of available drug therapies for melanoma are limited. The objective of the present study was to identify potential genes associated with melanoma progression and to explore approved therapeutic drugs that target these genes. Weighted gene co-expression network analysis was used to construct a gene co-expression network, explore the associations between genes and clinical characteristics and identify potential biomarkers. Gene expression profiles of the GSE65904 dataset were obtained from the Gene Expression Omnibus database. RNA-sequencing data and clinical information associated with melanoma obtained from The Cancer Genome Atlas were used for biomarker validation. A total of 15 modules were identified through average linkage hierarchical clustering. In the two significant modules, three network hub genes associated with melanoma prognosis were identified: C-X-C motif chemokine receptor 4 (CXCR4), interleukin 7 receptor (IL7R) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG). The receiver operating characteristic curve indicated that the mRNA levels of these genes exhibited excellent prognostic efficiency for primary and metastatic tumor tissues. In addition, the proximity between candidate genes associated with melanoma progression and drug targets obtained from DrugBank was calculated in the protein interaction network, and the top 15 drugs that may be suitable for treating melanoma were identified. In summary, co-expression network analysis led to the selection of CXCR4, IL7R and PIK3CG for further basic and clinical research on melanoma. Utilizing a network-based method, 15 drugs that exhibited potential for the treatment of melanoma were identified.

摘要

黑色素瘤是皮肤癌中最恶性的类型之一。然而,现有黑色素瘤药物疗法的疗效和实用性有限。本研究的目的是识别与黑色素瘤进展相关的潜在基因,并探索靶向这些基因的已批准治疗药物。加权基因共表达网络分析用于构建基因共表达网络,探索基因与临床特征之间的关联,并识别潜在的生物标志物。从基因表达综合数据库获得GSE65904数据集的基因表达谱。从癌症基因组图谱获得的与黑色素瘤相关的RNA测序数据和临床信息用于生物标志物验证。通过平均连锁层次聚类共识别出15个模块。在两个显著模块中,识别出与黑色素瘤预后相关的三个网络中心基因:C-X-C基序趋化因子受体4(CXCR4)、白细胞介素7受体(IL7R)和磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基γ(PIK3CG)。受试者工作特征曲线表明,这些基因的mRNA水平对原发性和转移性肿瘤组织具有优异的预后效率。此外,在蛋白质相互作用网络中计算了与黑色素瘤进展相关的候选基因与从药物银行获得的药物靶点之间的接近度,并识别出可能适合治疗黑色素瘤的前15种药物。总之,共表达网络分析导致选择CXCR4、IL7R和PIK3CG用于黑色素瘤的进一步基础和临床研究。利用基于网络的方法,识别出15种具有治疗黑色素瘤潜力的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/267c/6864934/da48d8d76ef4/ol-18-06-6066-g00.jpg

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