Molecular markers implicating early malignant events in cervical carcinogenesis

Area of Science:

• Oncology
• Molecular Biology
• Virology

Background:

• Human papillomavirus (HPV) can cause cervical lesions (CIN) that may progress to carcinoma.
• Accurate molecular markers are crucial for identifying CIN at high risk of malignant progression.
• hTERT activation is a potential indicator of irreversible malignant changes.

Purpose of the Study:

• To identify molecular markers that predict the progression of cervical intraepithelial neoplasia (CIN).
• To investigate the role of hTERT and viral oncogene expression in HPV-induced CIN progression.
• To evaluate a panel of genes as potential prognostic markers for CIN lesions.

Main Methods:

• Utilized the UT-DEC-1 cell line as an in vitro model for HPV-induced progression.
• Identified nine potential genes linking hTERT, viral oncogenes, and CIN2 phenotypes via molecular mining.
• Selected five genes (hTERT, DKC1, Bcl-2, S100A8, S100A9) for real-time PCR and immunohistochemistry analysis in 120 CIN lesions.

Main Results:

• Significant changes in mRNA expression of target genes were observed at three distinct time points during cellular progression.
• Overexpression of hTERT, Bcl-2, and S100A9 was detected in CIN lesions.
• The expression patterns of these genes changed progressively during the transition from CIN2 to CIN3 lesions.

Conclusions:

• Identified time points and gene overexpression patterns correlate with critical events in malignant progression, including viral integration and sustained telomerase activity.
• The combination of hTERT, Bcl-2, and S100A9 shows potential as a prognostic marker panel for assessing CIN lesions.
• Further validation in prospective clinical studies is necessary to confirm these findings.