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

被引:11
作者
Wang, Lu [1 ]
Wei, Chuan-Yuan [1 ]
Xu, Yuan-Yuan [2 ]
Deng, Xin-Yi [1 ]
Wang, Qiang [1 ]
Ying, Jiang-Hui [1 ]
Zhang, Si-Min [1 ]
Yuan, Xin [1 ]
Xuan, Tian-Fan [1 ]
Pan, Yu-Yan [1 ]
Gu, Jian-Ying [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Plast Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China
[2] Shanxi Med Univ, Dept Surg, Hosp 1, Taiyuan 030001, Shanxi, Peoples R China
关键词
melanoma; prognosis; drug repositioning; CHEMOKINE RECEPTOR CXCR4; LYMPH-NODE METASTASIS; PHASE-II; TARGETED THERAPY; OPEN-LABEL; EXPRESSION; CANCER; COMBINATION; SURVIVAL; OVEREXPRESSION;
D O I
10.3892/ol.2019.10961
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 gamma (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.
引用
收藏
页码:6066 / 6078
页数:13
相关论文
共 60 条
[1]   Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia [J].
Abou Dalle, Iman ;
Jabbour, Elias ;
Short, Nicholas J. ;
Ravandi, Farhad .
CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2019, 20 (01)
[2]   The identification of patient-specific mutations reveals dual pathway activation in most patients with melanoma and activated receptor tyrosine kinases in BRAF/NRAS wild-type melanomas [J].
Appenzeller, Silke ;
Gesierich, Anja ;
Thiem, Alexander ;
Hufnagel, Anita ;
Jessen, Christina ;
Kneitz, Hermann ;
Regensburger, Martina ;
Schmidt, Cornelia ;
Zirkenbach, Vanessa ;
Bischler, Thorsten ;
Schilling, Bastian ;
Siedel, Claudia ;
Goebeler, Maria-Elisabeth ;
Houben, Roland ;
Schrama, David ;
Gehrig, Andrea ;
Rost, Simone ;
Maurus, Katja ;
Bargou, Ralf ;
Rosenwald, Andreas ;
Schartl, Manfred ;
Goebeler, Matthias ;
Meierjohann, Svenja .
CANCER, 2019, 125 (04) :586-600
[3]   Management of melanoma in patients with chronic lymphocytic leukemia [J].
Archibald, William J. ;
Meacham, Philip J. ;
Williams, AnnaLynn M. ;
Baran, Andrea M. ;
Victor, Adrienne, I ;
Barr, Paul M. ;
Sahasrahbudhe, Deepak M. ;
Zent, Clive S. .
LEUKEMIA RESEARCH, 2018, 71 :43-46
[4]   Final Version of 2009 AJCC Melanoma Staging and Classification [J].
Balch, Charles M. ;
Gershenwald, Jeffrey E. ;
Soong, Seng-jaw ;
Thompson, John F. ;
Atkins, Michael B. ;
Byrd, David R. ;
Buzaid, Antonio C. ;
Cochran, Alistair J. ;
Coit, Daniel G. ;
Ding, Shouluan ;
Eggermont, Alexander M. ;
Flaherty, Keith T. ;
Gimotty, Phyllis A. ;
Kirkwood, John M. ;
McMasters, Kelly M. ;
Mihm, Martin C., Jr. ;
Morton, Donald L. ;
Ross, Merrick I. ;
Sober, Arthur J. ;
Sondak, Vernon K. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206
[5]   Cancer and the chemokine network [J].
Balkwill, F .
NATURE REVIEWS CANCER, 2004, 4 (07) :540-550
[6]   Gene Ontology Consortium: going forward [J].
Blake, J. A. ;
Christie, K. R. ;
Dolan, M. E. ;
Drabkin, H. J. ;
Hill, D. P. ;
Ni, L. ;
Sitnikov, D. ;
Burgess, S. ;
Buza, T. ;
Gresham, C. ;
McCarthy, F. ;
Pillai, L. ;
Wang, H. ;
Carbon, S. ;
Dietze, H. ;
Lewis, S. E. ;
Mungall, C. J. ;
Munoz-Torres, M. C. ;
Feuermann, M. ;
Gaudet, P. ;
Basu, S. ;
Chisholm, R. L. ;
Dodson, R. J. ;
Fey, P. ;
Mi, H. ;
Thomas, P. D. ;
Muruganujan, A. ;
Poudel, S. ;
Hu, J. C. ;
Aleksander, S. A. ;
McIntosh, B. K. ;
Renfro, D. P. ;
Siegele, D. A. ;
Attrill, H. ;
Brown, N. H. ;
Tweedie, S. ;
Lomax, J. ;
Osumi-Sutherland, D. ;
Parkinson, H. ;
Roncaglia, P. ;
Lovering, R. C. ;
Talmud, P. J. ;
Humphries, S. E. ;
Denny, P. ;
Campbell, N. H. ;
Foulger, R. E. ;
Chibucos, M. C. ;
Giglio, M. Gwinn ;
Chang, H. Y. ;
Finn, R. .
NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) :D1049-D1056
[7]   Network-based approach to prediction and population-based validation of in silico drug repurposing [J].
Cheng, Feixiong ;
Desai, Rishi J. ;
Handy, Diane E. ;
Wang, Ruisheng ;
Schneeweiss, Sebastian ;
Barabasi, Albert-Laszlo ;
Loscalzo, Joseph .
NATURE COMMUNICATIONS, 2018, 9
[8]   Molecular stratification of metastatic melanoma using gene expression profiling : Prediction of survival outcome and benefit from molecular targeted therapy [J].
Cirenajwis, Helena ;
Ekedahl, Henrik ;
Lauss, Martin ;
Harbst, Katja ;
Carneiro, Ana ;
Enoksson, Jens ;
Rosengren, Frida ;
Werner-Hartman, Linda ;
Torngren, Therese ;
Kvist, Anders ;
Fredlund, Erik ;
Bendahl, Par-Ola ;
Jirstrom, Karin ;
Lundgren, Lotta ;
Howlin, Jillian ;
Borg, Ake ;
Gruvberger-Saal, Sofia K. ;
Saal, Lao H. ;
Nielsen, Kari ;
Ringner, Markus ;
Tsao, Hensin ;
Olsson, Hakan ;
Ingvar, Christian ;
Staaf, Johan ;
Jonsson, Goran .
ONCOTARGET, 2015, 6 (14) :12297-12309
[9]   Trajectories of premalignancy during the journey from melanocyte to melanoma [J].
Colebatch, Andrew J. ;
Scolyer, Richard A. .
PATHOLOGY, 2018, 50 (01) :16-23
[10]   A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma [J].
da Silveira Nogueira Lima, Joao Paulo ;
Georgieva, Mina ;
Haaland, Benjamin ;
Lopes, Gilberto de Lima .
CANCER MEDICINE, 2017, 6 (06) :1143-1153