Relevance research between the expression of p16INK4a , Notch1, and hTERC genes: The development of HPV16-positive cervical cancer

J Clin Lab Anal. 2020 May;34(5):e23207. doi: 10.1002/jcla.23207. Epub 2020 Jan 24.

Abstract

Background: GLOBOCAN 2018 latest data show cervical cancer ranks fourth in morbidity and mortality among women. Many genes in cervical lesions differ in sensitivity and specificity. However, the diagnostic molecules for early cervical cancer are not very clear. This paper screens biomarkers for early molecular diagnosis of Mongolian patients with cervical cancer.

Methods: Immunohistochemical SP method was used to detect the expression of p16INK4a and Notch1 protein in paraffin sections of 226 Mongolian patients with HPV16-positive cervical lesions after pathological examination, and 100 of them were randomly selected by fluorescence in situ hybridization to detect hTERC gene. The HPV16-binding human cervical cancer SiHa cell line was used to silence the expression of HPV16 E6/E7 gene by RNA interference, and the expression of p16INK4a , Notch1, and hTERC genes and protein expression levels were detected by RT-PCR and Western blot.

Results: The positive expression rates of p16INK4a , Notch1, and hTERC genes in HPV16-positive cervical cancer, CIN-III, CIN-II, CIN-I, uterine leiomyoma, and chronic cervicitis were significantly different (P < .05); the positive expression rates of the three genes were also significantly different in the same type of cervical lesions (P < .05); RNA interference can effectively inhibit HPV16 E6/E7, p16INK4a and Notch1 gene expression, but has no effect on hTERC gene expression.

Conclusion: The p16INK4a gene can be used as a biomarker for early screening of cervical cancer, and the hTERC gene can be used to confirm the clinical diagnosis of cervical cancer.

Keywords: HPV16; Notch1 gene; SiHa cells; cervical cancer; hTERC gene; p16INK4a gene.

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Human papillomavirus 16 / pathogenicity
  • Humans
  • Oncogene Proteins, Viral / genetics
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • RNA / genetics*
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Repressor Proteins / genetics
  • Telomerase / genetics*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • E6 protein, Human papillomavirus type 16
  • NOTCH1 protein, human
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Receptor, Notch1
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • telomerase RNA
  • RNA
  • Telomerase