Gene expression profiling utilizing extremely sensitive CDNA arrays and enrichment-based network study of major bone cancer genes

Qiang Lin; Anum Munir; Sana Masood; Shahid Hussain; Mashal Naeem; Sahar Fazal

doi:10.4103/jrms.JRMS_592_20

Gene expression profiling utilizing extremely sensitive CDNA arrays and enrichment-based network study of major bone cancer genes

J Res Med Sci. 2021 Jul 31:26:49. doi: 10.4103/jrms.JRMS_592_20. eCollection 2021.

Authors

Qiang Lin¹, Anum Munir², Sana Masood², Shahid Hussain², Mashal Naeem³, Sahar Fazal²

Affiliations

¹ The First Department of Orthopedic Injury, Baoji Hospital of Traditional Chinese Medicine, Jintai District, Baoji City, Shanxi Province, China.
² Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences, Capital University of Science and Technology, Islamabad, Pakistan.
³ Department of Bioscience, Comsats Institute of Information Technology, Islamabad, Pakistan.

Abstract

Background: The gene interaction network is a set of genes interconnected by functional interactions among the genes. The gene interaction networks are studied to determine pathways and regulatory mechanisms in model organisms. In this research, the enrichment study of bone cancer-causing genes is undertaken to identify several hub genes associated to the development of bone cancer.

Materials and methods: Data on bone cancer is obtained from mutated gene samples; highly mutated genes are selected for the enrichment analysis. Due to certain interactions with each other the interaction network model for the hub genes is developed and simulations are produced to determine the levels of expression. For the array analyses, a total of 100 tumor specimens are collected. Cell cultures are prepared, RNA is extracted, cDNA arrays probes are generated, and the expressions analysis of Hub genes is determined.

Results: Out of cDNA array findings, only 7 genes: CDKN2A, AKT1, NRAS, PIK3CA, RB1, BRAF, and TP53 are differentially expressed and shown as significant in the development of bone tumors, approximately 15 pathways have been identified, including pathways for non-small cell lung cancer, prostate cancer, pancreatic cancer, chronic myeloid leukemia, and glioma, consisting of all the identified 7 genes. After clinical validations of tumor samples, the IDH1 and TP53 gene revealed significant number of mutations similar to other genes. Specimens analysis showed that RB1, P53, and NRAS are amplified in brain tumor, while BRAF, CDKN2A, and AKT1 are amplified in sarcoma. Maximum deletion mutations of the PIK3CA gene are observed in leukemia. CDKN2A gene amplifications have been observed in virtually all tumor specimens.

Conclusion: This study points to a recognizable evidence of novel superimposed pathways mechanisms strongly linked to cancer.

Keywords: Bone cancer; enrichment; gene ontology; network; phylogenetic analysis.