Mutation analysis of EGFR and its correlation with the HPV in Indian cervical cancer patients

Abstract

Cervical cancer is a major cause of morbidity and mortality particularly in developing countries. Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is associated with increased sensitivity to tyrosine kinase inhibitors (TKIs). In this study, the presence of EGFR mutations in cervical cancer and its correlation with HPV were identified. EGFR mutations were found in 31 out of 95 patients (32.63 %). Results showed the presence of EGFR mutations in 5.263 % of patients in exon 19. In exon 20, mutations were predominant in 25.26 % patients. While in exon 21, 8.421 % of patients had mutations. HPV, which is associated with cervical cancer development, was found in 95.78 % (HPVL1), 92.63 % (HPV16), and 3.15 % (HPV18) of patients. No correlation was found between HPV16 and EGFR mutations (p = 0.0616). Overall, mutations like V742R, Q787Q, Q849H, E866E, T854A, L858R, E872Q, and E688Q were found. Next, impact of TKI inhibitor (gefitinib) was checked with respect to presence or absence of mutation considering Q787Q mutation in exon 20 (G/A genotype) which is present in 25.2 % patients. Mutated cervical cancer cell lines showed higher sensitivity to gefitinib. Overall, this study suggests the importance of mutations in EGFR gene and indicates their relevance with respect to TKIs treatment in Indian cervical cancer patients.

The restraining effect of baicalein and U0126 on human cervical cancer cell line HeLa

“…Human papillomavirus (HPV) infection is one of the primary causes of cervical cancer tumorigenesis. HPV DNA can integrate into the cervical cells, and its encoded oncoprotein E6 will continue to activate the extracellular signal-regulated kinase (ERK1/2) signaling pathway, thus promoting cancerous processes and inhibiting apoptosis (2,3).…”

Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients

“…In India, cervix cancer is the second leading cause of mortality accounting 17% of all cancer deaths among women between the age group 30 and 69 years, which is about one-third of total deaths due to cervical cancer worldwide. 15 Annually, 6.7 lakh women die due to this disease 16 making this disease a primary major civic-related trouble for Indian women. The present study determines expression pattern, promoter hypermethylation and mutation of PTEN along with the clinical significance of the findings among cervix cancer patients from North Indian population to reinforce their implication in genesis, progression, and aggressiveness of cervix cancer.…”

Bcl-2-like Protein 11 (BIM) Expression Is Associated with Favorable Prognosis for Patients with Cervical Cancer

“…In EGFR-mutant lung cancer, EGFR tyrosine kinase inhibitors such as erlotinib and gefitinib effectively inhibit EGFR signaling, and so BIM up-regulation through EGFR inhibition is one of the important targets for tumor apoptosis (23,25). According to a recent report, EGFR mutation was observed in 32.6% of cervical cancer cases, and EGFR inhibition was effective in cell lines with EGFR mutations (26). Considering all of the above-noted results, BIM can be considered to be an important therapeutic target for EGFR-inhibition therapy; indeed, our favorable survival data for high BIM expression is evidence for application of EGFR inhibition to the treatment of EGFR-mutant cervical cancer.…”