TRANSCRIPTOME ANALYSIS OF STEM-LIKE CELLS DERIVED FROM CERVICAL CANCER PATIENTS AND PUTATIVE INTRINSIC CHEMORESISTANCE SIGNATURE

Cervical cancer (CC) represents a poignant public health issue of incidence and mortality in women worldwide. Treatment refractoriness to standard chemo and radiotherapy have unveiled the cancer stem cell (CSC) as a critical coordinator in the biological mechanisms to chemoresistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC-like) as bio markers related to intrinsic chemoresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited to the study. Fluorescence-activated cell sorting (FACS) was used to isolate enriched CD34+/CD45- CCSCs-like from tumour biopsies. Transcriptome was performed using SMART-Seq v4 Ultra-low Input RNA Kit (Takara) followed by library construction with Nextera® XT and sequencing in a NextSeq® 550 (Illumina). Bioinformatic analysis was done to identify differentially expressed genes (DEGs). We constructed the regulatory network of DEGs using Gene Ontology. The panel of bio markers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measure for diagnostic accuracy of quantitative tests. The analysis showed 1062 DEGs in CCSCs-like when comparing failure (N= 10) and success of treatment (N=21) in clinical outcome. Overlapping of the 20 highest AUC and pAUC values revealed five transcripts potentially implicated in innate chemoresistance (ILF2, SNX2, COPZ1, AC016722.1 and AL360175.1). This study provides a genomic signature that can be considered as potential bio markers in CC prognosis, treatment outcome and alternative targets to the forefront of cancer therapy, improving the evidence-based practice in clinical decision. Financial support: This study was funded by the Ministry of Health (Pronon grant number: 25000.159953/2014-18)