Molecular and bioinformatic analysis of apoptotic tumor suppressor genes in cervical cancer

Chetna Yadav1, Smiti Nanda2, Neelam Sehrawat1

  • 1Department of Genetics, Maharshi Dayanand University, Rohtak, 124001, India.

Insights

Aberrant methylation of apoptotic genes like DAPK, FAS, and TRAIL-R1 is linked to cervical cancer progression. These gene alterations correlate with HPV infection and clinicopathological factors, suggesting potential as biomarkers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cervical cancer is a significant global health issue.
  • Apoptosis plays a crucial role in cancer development and progression.
  • Aberrant gene methylation is implicated in various cancers, including cervical cancer.

Purpose of the Study:

  • To investigate the methylation status and mRNA expression of key apoptotic genes (DAPK, FAS, SMAC, TRAIL-R1) in cervical cancer.
  • To explore the association between gene methylation, mRNA expression, and clinicopathological factors in cervical cancer.
  • To evaluate the correlation with high-risk HPV types (16 and 18).

Main Methods:

  • Methylation-specific polymerase chain reaction (MSP) on 110 cervical cancer patients.
  • Real-time PCR for analyzing mRNA expression of selected apoptotic genes.
  • HPV typing (HPV 16 and 18) and association analysis with clinicopathological factors.
  • In-silico analysis for validation.

Main Results:

  • Significant differences in methylation status of DAPK, TRAIL-R1, SMAC, and FAS between cancer and normal tissues.
  • DAPK, FAS, and TRAIL-R1 were hypermethylated; SMAC was hypomethylated.
  • HPV 16/18 infections showed significant associations with methylation of DAPK, FAS, and TRAIL-R1.
  • Methylation was inversely correlated with DAPK, TRAIL-R1, and FAS expression.

Conclusions:

  • Aberrant promoter methylation of key apoptotic genes is significantly associated with cervical cancer.
  • These epigenetic alterations may contribute to cervical cancer progression.
  • The findings suggest potential of these genes as predictive biomarkers, especially in conjunction with HPV infection and clinicopathological factors.
  • Further research with larger cohorts and functional validation is warranted.

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