Exploring the p53 connection of cervical cancer pathogenesis involving north-east Indian patients

Abstract

Background As per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population. Methods Blood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies.

Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer

“…Previous studies also supported that SP1 is an important biomarker for CC [ 52 ]. Khan M.A et al revealed that TP53 has an association with cervical cancer pathogenesis [ 53 ]. NFYA promoted cell proliferation and tumorigenic properties by transcriptional activation of SOX2 in cervical cancer [ 54 ].…”

Elevated serum expression of p53 and association of TP53 codon 72 polymorphisms with risk of cervical cancer in Bangladeshi women

“…The majority of investigation of p53 protein in cervical cancer has been done in tissue biopsies with immunohistochemical staining [ 36 , 50 , 51 ]. To the best of our knowledge, only a limited number of studies investigated the serum p53 level in cervical cancer.…”

“…In contrast, reports of no significant difference in serum p53 levels between cervical cancer patients and controls have been reported in the Korean population [ 35 ]. A recent study in north-east Indian cervical cancer patients reported significant downregulation of p53 mRNA and protein in tissue biopsies compared to non-neoplastic control areas but a majority of the patients were affected with HPV infection [ 57 ] where viral oncogene E6 may be responsible for the degradation of the p53 protein [ 58 ]. So, p53 may be used as a peripheral biomarker only in cervical cancer patients without HPV infection.…”

“…A recent study in the North-East Indian population reported downregulation of p53 protein expression in tissue biopsies of cervical cancer patients compared to the non-neoplastic adjacent control region. Moreover, they reported that p53 protein was downregulated in lower grades (≤ stage III) of cervical cancer compared to higher grades (≥ stage III) [ 36 ]. In contrast, p53 expression was upregulated in stage IB1 cervical carcinoma in Taiwanese cervical cancer patients [ 37 ].…”

FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients

“…product. Standardized protocol of our laboratory ( Real et al, 2018 ; Sadaf et al, 2018 ; Khan et al, 2020 ) was used to perform PCR. Measurements were taken in triplicates.…”