Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression

被引：60
作者：
Palaniappan, Ashok [1 ]
Ramar, Karthick [1 ]
Ramalingam, Satish [1 ]
机构：
[1] Chettinad Acad Res & Educ, Fac Allied Hlth Sci, Kelambakkam 603103, Tamil Nadu, India
来源：
PLOS ONE | 2016年 / 11卷 / 05期
关键词：
GAMMA-GLUTAMYL-TRANSFERASE; MUTATED DRIVER PATHWAYS; PHOSPHOLIPASE C-GAMMA-1; CYTOSCAPE PLUGIN; CELL-SURVIVAL; HUMAN COLON; PROTEIN; EXPRESSION; GENE; OVEREXPRESSION;
D O I：
10.1371/journal.pone.0156665
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
It is well-known that the conversion of normal colon epithelium to adenoma and then to carcinoma stems from acquired molecular changes in the genome. The genetic basis of colorectal cancer has been elucidated to a certain extent, and much remains to be known about the identity of specific cancer genes that are associated with the advancement of colorectal cancer from one stage to the next. Here in this study we attempted to identify novel cancer genes that could underlie the stage-specific progression and metastasis of colorectal cancer. We conducted a stage-based meta-analysis of the voluminous tumor genome-sequencing data and mined using multiple approaches for novel genes driving the progression to stage-II, stage-III and stage-IV colorectal cancer. The consensus of these driver genes seeded the construction of stage-specific networks, which were then analyzed for the centrality of genes, clustering of subnetworks, and enrichment of gene-ontology processes. Our study identified three novel driver genes as hubs for stage-II progression: DYNC1H1, GRIN2A, GRM1. Four novel driver genes were identified as hubs for stage-III progression: IGF1R, CPS1, SPTA1, DSP. Three novel driver genes were identified as hubs for stage-IV progression: GSK3B, GGT1, EIF2B5. We also identified several non-driver genes that appeared to underscore the progression of colorectal cancer. Our study yielded potential diagnostic biomarkers for colorectal cancer as well as novel stage-specific drug targets for rational intervention. Our methodology is extendable to the analysis of other types of cancer to fill the gaps in our knowledge.
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页数：21
相关论文
共 95 条
[71]   Analyzing biological network parameters with CentiScaPe [J].
Scardoni, Giovanni ;
Petterlini, Michele ;
Laudanna, Carlo .
BIOINFORMATICS, 2009, 25 (21) :2857-2859
[72]   Cytoscape: A software environment for integrated models of biomolecular interaction networks [J].
Shannon, P ;
Markiel, A ;
Ozier, O ;
Baliga, NS ;
Wang, JT ;
Ramage, D ;
Amin, N ;
Schwikowski, B ;
Ideker, T .
GENOME RESEARCH, 2003, 13 (11) :2498-2504
[73]   Consistent and Differential Genetic Aberrations between Esophageal Dysplasia and Squamous Cell Carcinoma Detected By Array Comparative Genomic Hybridization [J].
Shi, Zhi-Zhou ;
Shang, Li ;
Jiang, Yan-Yi ;
Hao, Jia-Jie ;
Zhang, Yu ;
Zhang, Tong-Tong ;
Lin, De-Chen ;
Liu, Shu-Guang ;
Wang, Bo-Shi ;
Gong, Ting ;
Zhan, Qi-Min ;
Wang, Ming-Rong .
CLINICAL CANCER RESEARCH, 2013, 19 (21) :5867-5878
[74]   Genomic Alterations with Impact on Survival in Esophageal Squamous Cell Carcinoma Identified by Array Comparative Genomic Hybridization [J].
Shi, Zhi-Zhou ;
Liang, Jian-Wei ;
Zhan, Ting ;
Wang, Bo-Shi ;
Lin, De-Chen ;
Liu, Shu-Guang ;
Hao, Jia-Jie ;
Yang, Hai ;
Zhang, Yu ;
Zhan, Qi-Min ;
Zhang, Kai-Tai ;
Wang, Ming-Rong .
GENES CHROMOSOMES & CANCER, 2011, 50 (07) :518-526
[75]   Stratifin accelerates progression of lung adenocarcinoma at an early stage [J].
Shiba-Ishii, Aya ;
Kim, Yunjung ;
Shiozawa, Toshihiro ;
Iyama, Shinji ;
Satomi, Kaishi ;
Kano, Junko ;
Sakashita, Shingo ;
Morishita, Yukio ;
Noguchi, Masayuki .
MOLECULAR CANCER, 2015, 14
[76]   Aberrant Stratifin Overexpression Is Regulated by Tumor-Associated CpG Demethylation in Lung Adenocarcinoma [J].
Shiba-Ishii, Aya ;
Noguchi, Masayuki .
AMERICAN JOURNAL OF PATHOLOGY, 2012, 180 (04) :1653-1662
[77]  
Shiratsuchi I, 2011, ANTICANCER RES, V31, P2541
[78]   Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe [J].
Sureban, S. M. ;
Ramalingam, S. ;
Natarajan, G. ;
May, R. ;
Subramaniam, D. ;
Bishnupuri, K. S. ;
Morrison, A. R. ;
Dieckgraefe, B. K. ;
Brackett, D. J. ;
Postier, R. G. ;
Houchen, C. W. ;
Anant, S. .
ONCOGENE, 2008, 27 (33) :4544-4556
[79]   ModuLand plug-in for Cytoscape: determination of hierarchical layers of overlapping network modules and community centrality [J].
Szalay-Beko, Mate ;
Palotai, Robin ;
Szappanos, Balazs ;
Kovacs, Istvan A. ;
Papp, Balazs ;
Csermely, Peter .
BIOINFORMATICS, 2012, 28 (16) :2202-2204
[80]  
Tuominen H, 1996, BRIT J DERMATOL, V135, P576, DOI 10.1046/j.1365-2133.1996.d01-1043.x
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