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MiRNA expression profiling of locally advancer cervical cancer

ABSTRACT: MiRNA expression in totally 200 locally advanced cervical tumor biopsies were analysed by sequencing of small RNAs with Illumina HiSeq 2500. Based on the RNA isolation protocols, 90 samples were assigned to an experimental cohort, and 110 samples were assigned to a validation cohort (validation cohort1). The miRNA expression data was used to investigate miRNAs associated with prognosis and clinocopathological features in cervical cancer patients. Further we used the miRNA expression data to discover target genes by mathed sample miRNA-mRNA expression analysis with mRNA expression data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178629 | GEO | 2022/02/21

REPOSITORIES: GEO

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Project description:Purpose: We aimed to investigate the distinct transcriptional landscape in the poor responders to concurrent chemoradiotherapy (CCRT) and to gain mechanistic insights on treatment resistance in cervical cancer. Methods: RNA sequencing was performed using archived pre-treatment tissue biopsies of patients with locally advanced cervical cancer treated with concurrent platinum-based CCRT. Transcriptome data of patients with no durable benefit (NDB; progression-free period < 3 years) and durable clinical benefit (DCB; progression-free period > 5 years) after were compared. NDB score was estimated for each patient using the differentially expressed genes between NDB and DCB patients. Three independent cohorts, including The Cancer Genome Atlas cervical cancer (TCGA-CESC) cohort, were utilized for validation of NDB score. Potential response to PD-1 blockade was estimated with Tumor Immune Dysfunction and Exclusion (TIDE) score and T-cell-inflamed gene expression profile (GEP). Results: Patients with NDB exhibited a distinct transcriptional profile compared to those with DCB such as higher signatures of extracellular matrix organization and epithelial-to-mesenchymal transition. The fraction of cancer-associated fibroblasts (CAFs) within the tumor was significantly higher in NDB than DCB patients. Higher NDB score was significantly associated with poor survival in the TCGA-CESC cohort (n = 274; P = 0.015), but only in patients that received curative aim radiotherapy (P = 0.002) and not in patients who received other treatments (P = 0.57). The transcriptomic characteristics of patients with NDB were recapitulated in patients with high NDB score in TCGA-CESC. Patients with high NDB score displayed significantly higher TIDE prediction score and lower T-cell-inflamed GEP score compared to patients with low NDB scores. Conclusion: Cervical cancer patients with poor treatment outcome following CCRT exhibited a distinct gene signature that was able to predict treatment outcomes. For poor responders, immune checkpoint inhibitors may be less effective and CAF-targeting treatments may be a promising approach.

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MiRNA expression profiling of locally advancer cervical cancer

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