Does previous transurethral resection of the prostate negatively influence subsequent robotic-assisted radical prostatectomy in men diagnosed with prostate cancer? A systematic review and meta-analysis.

It is not uncommon to incidentally discover prostate cancer during the transurethral resection of the prostate (TURP) for the treatment of benign prostatic hyperplasia and necessitate a subsequent robotic-assisted radical prostatectomy (RARP). The study aims to evaluate whether TURP have negative influence on subsequent RARP. Through a literature search using MEDLINE, EMBASE and the Cochrane Library, 10 studies with 683 patients who underwent RARP after previous TURP and 4039 patients who underwent RARP only were identified for the purposes of the meta-analysis. Compared to standard RARP, RARP after TURP was related to longer operative time (WMD: 29.1 min, 95% CI: 13.3-44.8, P < 0.001), more blood loss (WMD: 49.3 ml, 95% CI: 8.8-89.7, P = 0.02), longer time to catheter removal (WMD: 0.93 days, 95% CI: 0.41-1.44, P < 0.001), higher rates of overall (RR: 1.45, 95% CI: 1.08-1.95, P = 0.01) and major complications (RR: 3.67, 95% Cl: 1.63-8.24, P = 0.002), frequently demand for bladder neck reconstruction (RR: 5.46, 95% CI: 3.15-9.47, P < 0.001) and lower succeed in nerve sparing (RR: 0.73, 95% CI: 0.62-0.87, P < 0.001). In terms of quality of life, there are worse recovery of urinary continence (RR of incontinence rate: RR: 1.24, 95% CI: 1.02-1.52, P = 0.03) and potency (RR: 0.8, 95% CI: 0.73-0.89, P < 0.001) at 1 year in RARP with previous TURP. In addition, the RARP with previous TURP had greater percentage positive margins (RR: 1.24, 95% CI: 1.02-1.52, P = 0.03), while there is no difference in length of stay and biochemical recurrence rate at 1 year. RARP is feasible but challenging after TURP. It significantly increases the difficulty of operation and compromises surgical, functional and oncological outcomes. It is important for urologists and patients to be aware of the negative impact of TURP on subsequent RARP and establish treatment strategies to lessen the adverse effects.

YTHDC1 is downregulated by the YY1/HDAC2 complex and controls the sensitivity of ccRCC to sunitinib by targeting the ANXA1-MAPK pathway.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) such as sunitinib are multitarget antiangiogenic agents in clear cell renal cell carcinoma (ccRCC). They are widely used in the treatment of advanced/metastatic renal cancer. However, resistance to TKIs is common in the clinic, particularly after long-term treatment. YTHDC1 is the main nuclear reader protein that binds with m6A to regulate the splicing, export and stability of mRNA. However, the specific role and corresponding mechanism of YTHDC1 in renal cancer cells are still unclear. METHODS: The Cancer Genome Atlas (TCGA) dataset was used to study the expression of YTHDC1 in ccRCC. Cell counting kit-8 (CCK-8), wound healing, Transwell and xenograft assays were applied to explore the biological function of YTHDC1 in ccRCC. Western blot, quantitative real time PCR (RT‒qPCR), RNA immunoprecipitation PCR (RIP-qPCR), methylated RIP-qPCR (MeRIP-qPCR) and RNA sequencing (RNA-seq) analyses were applied to study the YY1/HDAC2/YTHDC1/ANXA1 axis in renal cancer cells. The CCK-8 assay and xenograft assay were used to study the role of YTHDC1 in determining the sensitivity of ccRCC to sunitinib. RESULTS: Our results demonstrated that YTHDC1 is downregulated in ccRCC tissues compared with normal tissues. Low expression of YTHDC1 is associated with a poor prognosis in patients with ccRCC. Subsequently, we showed that YTHDC1 inhibits the progression of renal cancer cells via downregulation of the ANXA1/MAPK pathways. Moreover, we also showed that the YTHDC1/ANXA1 axis modulates the sensitivity of tyrosine kinase inhibitors. We then revealed that HDAC2 inhibitors resensitize ccRCC to tyrosine kinase inhibitors through the YY1/HDAC2 complex. We have identified a novel YY1/HDAC2/YTHDC1/ANXA1 axis modulating the progression and chemosensitivity of ccRCC. CONCLUSION: We identified a novel YY1/HDAC2/YTHDC1/ANXA1 axis modulating the progression and chemosensitivity of ccRCC.