Mp58-13 the Role of G8 Screening Tool in Elderly Population Undergoing Radical Cystectomy: Preliminary Evaluation

Abstract

The molecular mechanisms of muscle invasion in bladder cancer (BC) are still unknown. Based on the microRNA (miRNA) signature of BC by deep sequencing, we recently found that several double-stranded mature miRNAs derived from the same pre-miRNAs acted as tumor suppressors by regulating common target genes. In this study, we focused on miR-199 family members (miR-199a-3p/-5p and miR-199b-3p/-5p) that were downregulated in the signature. The aim of this study was to investigate the functional role of miR-199 family members and to identify molecular targets that contribute to tumor invasion in BC.METHODS: Expression levels of these miRNAs in 32 BC clinical samples and 12 normal bladder epithelia (NBE) and cell lines (T24 and BOY) were evaluated by qRT-PCR. Cell proliferation, migration, and invasion assays were performed in these miRNAs transfected BC cells. In silico analysis by using TargetScan and GEO database were applied to identify candidate target genes of these miRNAs. Luciferase reporter assays were carried out to determine whether these miRNAs directly bind to the target gene. We performed loss-of-function studies by using si-RNA transfectants to evaluate the functional role of target gene. We confirmed the target gene expression and the correlations between miR-199 family and the target gene expression by The Cancer Genome Atlas (TCGA) database (408 BCs and 19 NBE).RESULTS: The expression levels of these miRNAs were significantly reduced in clinical BCs (P < 0.005). Restoration of these miRNAs significantly inhibited cell migration and invasion in BC cells (P < 0.0001). Luciferase reporter assays identified integrin a3 (ITGA3) as a target gene directly regulated by these miRNAs. TCGA database showed that ITGA3 expression was significantly upregulated in BC compared with NBE (P ¼ 0.0063) and there were significant negative correlations between ITGA3 and miR-199 family expression (P < 0.05). Immunohistochemistry demonstrated ITGA3 expression was significantly upregulated in BCs compared with NBE (P ¼ 0.0038) and highly expressed in patients with advanced tumor stage (T2 or more) (P ¼ 0.048). Loss-of-function study showed that cell migration and invasion were significantly inhibited in si-ITGA3 transfectans (P < 0.0001).CONCLUSIONS: Recent studies showed that ITGA3 functions as extracellular matrix (ECM) receptor and contributes to cancer cell migration and invasion. Our data suggested that ITGA3 was directly regulated by miR-199 family and could be a novel therapeutic target in BC.

Reliable Prediction of Post-Operative Complications’ Rate Using the G8 Screening Tool: A Prospective Study on Elderly Patients Undergoing Surgery for Kidney Cancer

“…Over time, the G8 score has been studied in various declinations and clinical fields, demonstrating how its use has proven useful and statistically significant [24][25][26][27]. Several studies have been conducted in the surgical setting too, demonstrating the versatility and functionality of the G8 screening tool [28][29][30][31]. In particular, a prospective trial was conducted with the aim to validate G8 as a screening tool in older cancer patients diagnosed with solid neoplasia candidates for surgical treatment, in order to identify those who needed extended CGA.…”