ATF4, ZIK1, and PNMA3 Transcriptomic Signatures Predict Chemoradiotherapy Response in Cervical Cancer

Area of Science:

• Oncology
• Genomics
• Biomarkers

Background:

• Cervical cancer (CC) is a leading global malignancy in women with high mortality.
• Chemoradiotherapy resistance significantly impacts CC treatment outcomes.
• Prognostic biomarkers are crucial for tailoring therapeutic strategies in CC patients.

Purpose of the Study:

• To identify gene expression signatures for predicting treatment response in cervical cancer patients.
• To discover potential biomarkers for assessing chemoradiotherapy outcomes.
• To investigate gene expression profiles in non-stem CC cells related to treatment response.

Main Methods:

• Analysis of non-stem cervical cancer cells from responder and non-responder patients using Fluorescence-activated Cell Sorting.
• Next-generation RNA sequencing to evaluate differential gene expression profiles.
• Machine learning and statistical analyses to identify gene signatures associated with clinical outcomes.

Main Results:

• 2670 differentially expressed genes (DEGs) were identified between responder and non-responder groups.
• Eight genes were found relevant for classifying treatment response; PNMA3 and ZIK1 were upregulated in non-responders.
• ATF4 and PNMA3, in conjunction with ZIK1, showed differential expression in non-stem CC cells and were linked to apoptosis pathways.

Conclusions:

• Upregulation of PNMA3 and ZIK1, with concurrent ATF4 downregulation in cervical cancer non-stem cells, is associated with resistance to apoptosis and chemoradiotherapy.
• These identified genes (PNMA3, ZIK1, ATF4) show potential as prognostic signatures for cervical cancer.
• The findings highlight the importance of non-stem cell gene expression in predicting CC treatment response.