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Cervical Cancer Stem-Like Cell Transcriptome Profiles Predict Response to Chemoradiotherapy.
Luciana W Zuccherato1, Christina M T Machado1, Wagner C S Magalhães1
1Núcleo de Ensino e Pesquisa - Instituto Mário Penna, Belo Horizonte, Brazil.
Frontiers in Oncology
|May 24, 2021
Summary
Researchers identified gene expression differences in cervical cancer stem-like cells (CCSC) to predict treatment resistance. These findings offer potential biomarkers for cervical cancer (CC) prognosis and new therapeutic targets.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- Cervical cancer (CC) is a global health challenge, with treatment resistance often linked to cancer stem cells (CSCs).
- Understanding the genetic basis of chemoradiotherapy resistance in CC is crucial for improving patient outcomes.
- Cervical cancer stem-like cells (CCSC) play a key role in treatment refractoriness and recurrence.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in CCSCs as potential biomarkers for intrinsic chemoradiotherapy resistance in cervical cancer.
- To evaluate the diagnostic and prognostic value of these DEGs for predicting treatment response and survival in CC patients.
- To explore novel therapeutic targets based on the identified gene expression signatures.
Main Methods:
- Recruitment of 31 locally advanced cervical cancer patients.
- Isolation and enrichment of CD34+/CD45- CCSCs using fluorescence-activated cell sorting.
- Ultra-low input RNA sequencing to perform transcriptome analysis.
- Identification of DEGs by comparing Non-Responder (NR) and Responder (R) groups using Log2 fold change and adjusted p-value < 0.05.
- Biomarker selection using Area Under the ROC Curve (AUC) and partial AUC (pAUC) analysis.
Main Results:
- 1050 DEGs were identified between NR and R patient groups.
- A significant number of underexpressed coding genes, lncRNAs, and miRNAs were found in NR patients.
- Seven genes (ILF2, RBM22P2, ACO16722.1, AL360175.1, AC092354.1) showed high diagnostic capacity for distinguishing NR vs. R patients.
- Four of these genes were also associated with significant survival Hazard Ratios.
Conclusions:
- DEG signatures in CCSCs can serve as potential biomarkers for cervical cancer prognosis and treatment outcomes.
- The identified genes offer potential for predicting patient response to chemoradiotherapy.
- These findings highlight potential alternative therapeutic targets for cervical cancer treatment.
