Cover Image

Structural and Functional Analysis of Crucial Protein Complex in Basal Cell Skin Carcinoma via Network Construction

Mona Zamanian Azodi, Mostafa Rezaei-Tavirani, Majid Rezaei-Tavirani, Mohammad Rostami-Nejad

 Background: The basal-cell carcinoma (BCC) as one of the most common type of skin cancers reported to have an increasing trend during past years. Molecular approaches can be useful to advance diagnosis and treatment goals in this cancer.Materials and Methods: In this sense, one of the recent popular investigations, protein-protein interaction network analysis (PPI), was  applied in this study to better facilitate molecular view of BCC.  Cytoscape v3.6.0 and its plug-ins analyzed and explored the topological and annotation features of the constructed network. Result: Among TP53, EGFR, AKT1, ERBB2, HRAS, and CCND1 as central agents of the network, five of them were also present in the first prominent cluster of the network in which considered for further analysis. It is suggested that there are significant related biological processes, actions, and expression changes for this highlighted cluster that may be related to BCC risk.  Conclusion: Therefore, the studied complex of proteins may worth considering for clinical studies and therapeutic interventions after validating by related tests. What is more, among these genes, EBBR2 has more to offer and consequently with additional values.  [GMJ.2018;7:e1271]

Protein Interaction Maps; Gene Ontology; Protein Complex; Skin Neoplasm

Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. New England Journal of Medicine. 2009;361(12):1164-72.

Wong C, Strange R, Lear J. Basal cell carcinoma. BMJ: British Medical Journal. 2003;327(7418):794-98.

Hoorens I, Vossaert K, Ongenae K, Brochez L. Is early detection of basal cell carcinoma worthwhile? Systematic review based on the WHO criteria for screening. British Journal of Dermatology. 2016;174(6):1258-65.

Clark CM, Furniss M, Mackay-Wiggan JM. Basal cell carcinoma: an evidence-based treatment update. American journal of clinical dermatology. 2014;15(3):197-216.

Stacey SN, Helgason H, Gudjonsson SA, Thorleifsson G, Zink F, Sigurdsson A et al. New basal cell carcinoma susceptibility loci. Nature communications. 2015;6825(6): 1-10.

Brohee S, Van Helden J. Evaluation of clustering algorithms for protein-protein interaction networks. BMC bioinformatics. 2006;7(1):1-19.

Zamanian Azodi M, Rezaei Tavirani M, Arefi Oskouie A, Mansouri V, Hamdieh M, Nejati N et al. Introducing Transthyretin as a Differentially Expressed Protein in Washing Subtype of Obsessive-Compulsive Disorder. Basic and Clinical Neuroscience. 2018;9(3):187-94.

Tavirani MR, Mansouri V, Tavirani SR, Tackallou SH, Rostami-Nejad M. Gliosarcoma Protein-Protein Interaction Network Analysis and Gene Ontology. International Journal of Cancer Management. 2018(In Press).

Liu X, Yang Z, Zhou Z, Sun Y, Lin H, Wang J et al. The impact of protein interaction networks' characteristics on computational complex detection methods. Journal of theoretical biology. 2018;439:141-51.

Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC bioinformatics. 2003;4(1):1-27.

Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010;27(3):431-2.

Jeong H, Mason SP, Barabási A-L, Oltvai ZN. Lethality and centrality in protein networks. Nature. 2001;411(6833):41-42.

Sand M, Bechara FG, Sand D, Gambichler T, Hahn SA, Bromba M et al. Long-noncoding RNAs in basal cell carcinoma. Tumor Biology. 2016;37(8):10595-608.

Liu Y, Chen C, Xu Z, Scuoppo C, Rillahan CD, Gao J et al. Deletions linked to TP53 loss drive cancer through p53-independent mechanisms. Nature. 2016;531(7595):471-75.

Nicholson R, Gee J, Harper M. EGFR and cancer prognosis. European journal of cancer. 2001;37:9-15.

Segrelles C, Lu J, Hammann B, Santos M, Moral M, Cascallana JL et al. Deregulated activity of Akt in epithelial basal cells induces spontaneous tumors and heightened sensitivity to skin carcinogenesis. Cancer research. 2007;67(22):10879-88.

Ullrich SE. Sunlight and skin cancer: lessons from the immune system. Molecular carcinogenesis. 2007;46(8):629-33.

Arnault JP, Mateus C, Escudier B, Tomasic G, Wechsler J, Hollville E et al. Skin tumors induced by sorafenib; paradoxic RAS–RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Clinical cancer research. 2012;18(1):263-72.

Utikal J, Udart M, Leiter U, Kaskel P, Peter RU, Krähn G. Numerical abnormalities of the Cyclin D1 gene locus on chromosome 11q13 in non-melanoma skin cancer. Cancer letters. 2005;219(2):197-204.

Smyth I, Narang MA, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G et al. Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene in basal cell carcinoma and medulloblastoma on chromosome 1p32. Human molecular genetics. 1999;8(2):291-7.

Rezaei-Tavirani M, Zamanian-Azodi M, Rajabi S, Masoudi-Nejad A, Rostami-Nejad M, Rahmatirad S. Protein Clustering and Interactome Analysis in Parkinson and Alzheimer's Diseases. Archives of Iranian Medicine (AIM). 2016;19(2):101-109.

Rezaei–Tavirani M, Bashash D, Rostami FT, Tavirani SR, Nikzamir A, Tavirani MR et al. Celiac disease microarray analysis based on system biology approach. Gastroenterology and Hepatology from bed to bench. 2018; 11(3): 216-224.


  • There are currently no refbacks.