Anais da Academia Brasileira de Ciências

Prognostic significance and therapeutic outcome prediction through serum miR-21 and miR-145 in ovarian cancer

Abstract This study investigated the diagnostic value of serum microRNA-21 (miR-21) and miR-145 in assessing the treatment response and prognosis of ovarian cancer patients. A total of 139 patients enrolled in this study were categorized based on their chemotherapy outcomes into three groups: partial response, stable disease, and disease progression. Significant differences in serum levels of miR-21 and miR-145 among these groups were observed. Specifically, elevated miR-21 and reduced miR-145 levels were associated with worse treatment outcomes and poorer prognoses. Multivariate logistic regression analysis identified miR-21 and miR-145, along with age, tumor stage, and lymph node metastasis, as independent predictors of patient outcomes. The receiver operating curve (ROC) analysis indicated that the combination of miR-21 and miR-145 provided higher accuracy in predicting patient prognosis compared to each biomarker alone. The findings suggest that miR-21 and miR-145 can be effective supplementary tools for evaluating treatment effectiveness and prognostic assessments in ovarian cancer patients.

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.

Plasma antioxidant capacity in cervical cancer patients

The oxidative pathway and the alteration of the antioxidant defense have drawn attention to the pathophysiology of cervical cancer (CC). In our preliminary study, it was possible to corroborate the findings regarding the antioxidants of patients affected by CC. The total antioxidant activity and lipid peroxidation (LP) were evaluated in 14 people diagnosed with CC and 14 volunteers without CC (control group). Results showed low antioxidant activity in CC group. LP was not significant when analyzing CC group and control group. Our results indicate that changes in antioxidant defense may contribute to the pathophysiology of CC.

Fatty acid synthase as a potential new therapeutic target for cervical cancer

Fatty acid synthase (FASN) is the rate-limiting enzyme for the de novo synthesis of fatty acids in the cytoplasm of tumour cells. Many tumour cells express high levels of FASN, and its expression is associated with a poorer prognosis. Cervical cancer is a major public health problem, representing the fourth most common cancer affecting women worldwide. To date, only a few in silico studies have correlated FASN expression with cervical cancer. This study aimed to investigate in vitro FASN expression in premalignant lesions and cervical cancer samples and the effects of a FASN inhibitor on cervical cancer cells. FASN expression was observed in all cervical cancer samples with increased expression at more advanced cervical cancer stages. The FASN inhibitor (orlistat) reduced the in vitro cell viability of cervical cancer cells (C-33A, ME-180, HeLa and SiHa) in a time-dependent manner and triggered apoptosis. FASN inhibitor also led to cell cycle arrest and autophagy. FASN may be a potential therapeutic target for cervical cancer, and medicinal chemists, pharmaceutical researchers and formulators should consider this finding in the development of new treatment approaches for this cancer type.