Investigator
Unknown Institution
Membrane transporter genes predict chemoradiotherapy response in patients with cervical cancer
This study aimed to explore membrane transporter gene expression as a predictive biomarker of chemoradiotherapy response in cervical cancer. The differential expression of ATP1B3 and SLCO1B3 accurately classified patients as responders or non-responders with 90% accuracy, highlighting their potential for personalized treatment strategies. Two gene groups with contrasting expression profiles were identified. The ATP1B3 and SLCOB3 gene profiles classified patients with 90% accuracy. The ATP1B3 and SLCOB3 gene signature is a potential predictor of treatment response. Cervical cancer is the fourth most common cancer in women worldwide. Resistance to chemoradiotherapy in cervical cancer has been widely associated with membrane transport-related genes, particularly those encoding efflux transport proteins, such as the ATP-binding cassette family members (including P-glycoprotein), which act by expelling chemotherapeutic agents from tumor cells, as well as solute carrier proteins, whose expression impairs the uptake of antineoplastic drugs by cancer cells. This study aimed to identify specific membrane transport-related gene expression profiles as potential biomarkers for predicting chemoradiotherapy response in cervical cancer. Cervical biopsies were collected from 31 patients (21 responders and 10 non-responders) at Hospital Luxemburgo - Instituto Mário Penna. Fluorescence-activated cell sorting was used to separate non-stem cancer cells from cervical cancer biopsies. cDNA libraries from the 21 responders and 10 non-responders were sequenced using the Illumina platform. Expression analysis was performed using R and the DESeq2 package, with differentially expressed genes identified based on log fold change >1 or <-1 and padj ≤0.05. WEKA software and decision tree methods were used to analyze membrane transporters. The results revealed two major gene groups with contrasting differentially expressed genes profiles. The first group, comprising SLC35 and ATP13, was overexpressed in non-responders, while the second group, consisting of SLC25 and ATP6, was overexpressed in responders. Decision tree analysis revealed that ATP1B3 and SLCOB3 expression profiles accurately classified patients into responder and non-responder groups with 90% accuracy, indicating that ATP1B3 and SLCOB3 are potential predictors of chemoradiotherapy response. Our results strongly suggest the presence of a candidate gene signature comprising ATP1B3 and SLCO1B3 that holds predictive value for chemoradiotherapy response in cervical cancer.
Association of a CHEK2 somatic variant with tumor microenvironment calprotectin expression predicts platinum resistance in a small cohort of ovarian carcinoma
High-grade serous ovarian cancer (HGSOC) low overall survival rate is often attributed to platinum resistance. Recent studies suggest that the tumor associated-microenvironment (TME) is a determining factor in malignant tumor progression and DNA damage plays a crucial role in this process. Here, we sought to identify platinum resistance biomarkers associating the TME immune profile and the mutational landscape of the homologous repair pathway genes with the HGSOC patients prognosis and response to chemotherapy. Using a decision tree classifier approach, we found that platinum resistant (PR) patients were characterized by the presence of a novel deep intronic variant, the CHEK2 c.319+ 3943A > T, and higher L1 expression (p = 0.016), (100% accuracy). Chek2 protein is an important component of DNA repair and L1, also known as calprotectin, is one component of the neutrophil extracellular traps (NETs) during inflammation, previously suggested as a key contributor to the metastatic process in HGSOC. Also, PD-L2 levels were significantly higher in PR patients positive for this CHEK2 variant (p = 0.048), underscoring the need to explore its potential therapeutic role for this cancer. Our results suggest an interplay between TME and DNA repair variants that results in a multifactorial nature of HGSOC resistance to platinum chemotherapy.
Validation of cervical cancer genetic signature in minimally invasive samples
Abstract Cervical cancer remains the leading cause of cancer death in 36 countries, and high-risk human papillomavirus types are responsible for most cases. Identifying strategies to make treatment more targeted and effective has become a priority. This study aims to validate a set of differentially expressed genes previously identified in cervical cancer stem cells as predictive biomarkers for response to chemoradiotherapy using minimally invasive samples. Additionally, it aims to elucidate the relationship between high-risk human papillomavirus infection and cervical cancer patients’ response to treatment. Gene expression for three differentially expressed genes (COPZ1, ILF2, and SNX2) was evaluated from 20 cervical cancer patients’ cervical cytology brushes. Unmapped reads from the same transcriptome were used to evaluate the presence of human papillomavirus in tumor tissue through qualitative screening of 13 high-risk human papillomavirus types. Our study did not clarify the relationship between high-risk human papillomavirus infection and the treatment response. However, we found downregulation of COPZ1 in patients who responded to treatment compared to non-responders, and ILF2 in patients with more advanced tumor stages. This suggests that COPZ1 and ILF2 expressions are potential cervical cancer prognostic biomarkers that can be assessed using samples commonly used in clinical practice.
