title: Potential therapeutic targets for oral cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70.
abstract: In India, oral cancer has consistently ranked among top three causes of cancer-related deaths, and it has emerged as a top cause for the cancer-related deaths among men. Lack of effective therapeutic options is one of the main challenges in clinical management of oral cancer patients. We interrogated large pool of samples from oral cancer gene expression studies to identify potential therapeutic targets that are involved in multiple cancer hallmark events. Therapeutic strategies directed towards such targets can be expected to effectively control cancer cells. Datasets from different gene expression studies were integrated by removing batch-effects and was used for downstream analyses, including differential expression analysis. Dependency network analysis was done to identify genes that undergo marked topological changes in oral cancer samples when compared with control samples. Causal reasoning analysis was carried out to identify significant hypotheses, which can explain gene expression profiles observed in oral cancer samples. Text-mining based approach was used to detect cancer hallmarks associated with genes significantly expressed in oral cancer. In all, 2365 genes were detected to be differentially expressed genes, which includes some of the highly differentially expressed genes like matrix metalloproteinases (MMP-1/3/10/13), chemokine (C-X-C motif) ligands (IL8, CXCL-10/-11), PTHLH, SERPINE1, NELL2, S100A7A, MAL, CRNN, TGM3, CLCA4, keratins (KRT-3/4/13/76/78), SERPINB11 and serine peptidase inhibitors (SPINK-5/7). XIST, TCEAL2, NRAS and FGFR2 are some of the important genes detected by dependency and causal network analysis. Literature mining analysis annotated 1014 genes, out of which 841 genes were statistically significantly annotated. The integration of output of various analyses, resulted in the list of potential therapeutic targets for oral cancer, which included targets such as ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF and CD70.
authors.affiliation: Defence Research Development Establishment, Defence Research Development Organization, Ministry of Defence, Govt. of India, Gwalior, Madhya Pradesh, India; Department of Postgraduate Studies & Research in Biological Sciences, Rani Durgavati University, Jabalpur, Madhya Pradesh, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bundela
authors.affiliation: Department of Postgraduate Studies & Research in Biological Sciences, Rani Durgavati University, Jabalpur, Madhya Pradesh, India.
authors.forename: Anjana
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Defence Research Development Establishment, Defence Research Development Organization, Ministry of Defence, Govt. of India, Gwalior, Madhya Pradesh, India; School of Studies in Biotechnology, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Bisen
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism; D053282:CD27 Ligand / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D057225:Data Mining; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007194:India; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D058977:Molecular Sequence Annotation; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C507862:ADM protein, human; C526317:CCN2 protein, human; D053282:CD27 Ligand; C505771:CD70 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D055513:Connective Tissue Growth Factor; D053607:Adrenomedullin; C512478:EGFR protein, human; D066246:ErbB Receptors; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases