Stella Di Costanzo

miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy

AbstractEndometrial cancer (EC) is the most prevalent gynecological cancer in high‐income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity‐related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR‐199a‐5p, miR‐449a, miR‐449b‐5p) in normal‐weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity‐related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity‐related pathways and that may provide novel implications for the clinical management of obese EC patients.

Optimal number of neoadjuvant chemotherapy cycles prior to interval debulking surgery in advanced epithelial ovarian cancer: a systematic review and meta-analysis of progression-free survival and overall survival

Neoadjuvant chemotherapy (NACT) represents a treatment option in patients with advanced epithelial ovarian cancer (AEOC) who are not good candidates for primary debulking surgery. Usually, 3 cycles of chemotherapy before surgery have been considered the best option for patient survival, although quite often some patients receive more than 3 cycles. The aim of this systematic review and meta-analysis was to identify the optimal number of NACT cycles reporting better survival in AEOC patients. PubMed, Cochrane Library, and Scopus were searched for original articles that analyzed the relationship between the number of chemotherapy cycles and clinical outcomes in AEOC patients before interval debulking surgery (IDS). The main outcomes were progression-free survival (PFS) and overall survival (OS). A total of 22 studies comprising 7,005 patients diagnosed with AEOC were included in our analysis. In terms of survival, the reviewed studies dividing the patients in ≤3 NACT cycles vs. >3, showed a trend for a decrease in PFS and a significant reduction in OS with an increasing number of cycles, while a difference in both PFS and OS was revealed if early IDS included patients with 4 NACT cycles. These results should be interpreted with caution due to the complex characteristics of AEOC patients. In conclusion, our review and meta-analysis revealed that there is not enough evidence to determine the optimal number of NACT treatments before surgery. Further research in the form of well-designed randomized controlled trials is necessary to address this issue. PROSPERO Identifier: CRD42022334959.