Carolina Pereira de Souza Melo

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.