Affiliations 

  • 1 Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
  • 2 Health Sciences Division, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi P.O. Box 25026, United Arab Emirates
  • 3 Faculty of Health and Life Sciences, INTI International University, Persiaran Perdana BBN, Putra Nilai, Nilai 71800, Malaysia
  • 4 He & Ni Academy, Office Tower B, Northpoint Mid Valley City, Kuala Lumpur 59200, Malaysia
  • 5 School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Malaysia
Int J Mol Sci, 2022 Nov 18;23(22).
PMID: 36430761 DOI: 10.3390/ijms232214285

Abstract

The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.