A Notch signaling-related lncRNA signature for predicting prognosis and therapeutic response in clear cell renal cell carcinoma.

Increasing evidence has confirmed the vital role of Notch signaling in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). The underlying function of long non-coding RNA (lncRNA) related to Notch signaling in ccRCC remains unclear. In present study, the prognostic value and therapeutic strategy of Notch signaling-related lncRNA are comprehensively explored in ccRCC. In total, we acquired 1422 NSRlncRNAs, of which 41 lncRNAs were identified the key NSRlncRNAs associated with the occurrence of ccRCC. The prognostic signature containing five NSRlncRNAs (AC092611.2, NNT-AS1, AGAP2-AS1, AC147651.3, and AC007406.3) was established and validated, and the ccRCC patients were clustered into the high- and low-risk groups. The overall survival of patients in the low-risk group were much more favorable than those in the high-risk group. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic biomarker. Based on the risk score and clinical variables, a nomogram for predicting prognosis of ccRCC patients was constructed, and the calibration curves and DCA curves showed the superior predictive ability of nomogram. The risk score was correlated with immune cell infiltration, targeted therapy or chemotherapy sensitivity, and multiple oncogenic pathways. Additionally, consensus clustering analysis stratified the ccRCC patients into four clusters with obvious different outcomes, immune microenvironments, and expression of immune checkpoints. The constructed NSRlncRNA-based signature might serve as a potential biomarker for predicting prognosis and response to immunotherapy or targeted therapy in patients with ccRCC.

Quantitative Analysis of Quality of Life and Exploration of Influencing Factors in Patients Undergoing Radical Prostatectomy.

OBJECTIVE: To quantify and evaluate the quality of life of patients undergoing radical prostatectomy using the FACT-P scoring system, and to explore the predictive factors for postoperative quality of life. METHODS: Clinical data of 249 patients who underwent radical prostatectomy in our hospital from January 2021 to October 2022 were analyzed. According to the surgical method and whether the subjective quality of life of the patient decreased significantly, the patients were divided into groups, and the predictive factors for changes in subjective quality of life after surgery were analyzed. RESULTS: A total of 192 cases were finally obtained (45 cases of fascia internal approach, 147 cases of traditional radical prostatectomy), and patients who underwent fascia internal approach (FACT-P: 110.15 ± 10.55) had better postoperative quality of life than those who underwent extra-fascial radical prostatectomy (FACT-P: 102.30 ± 6.75) (P < .01). One hundred fourteen patients reported a decrease in subjective quality of life, while 78 did not. The preoperative FACT-P score was an independent predictive factor (OR=0.719, P < .01), and when the preoperative score was <116 points, the possibility of no decrease in quality of life after surgery was higher. CONCLUSION: Fascia internal approach should be performed as much as possible for suitable surgical patients, and for patients with a preoperative FACT-P score ≥116 points, the possibility of a decrease in quality of life after surgery should be fully communicated.

Case report: durable complete response to pembrolizumab plus lenvatinib in a metastatic upper tract urothelial carcinoma patient with high tumor mutational burden and an immune-active tumor microenvironment.

Immune checkpoint inhibitors (ICIs) have been approved as an emerging first-line treatment option for advanced and metastatic urothelial carcinoma whose tumors express programmed death-ligand 1 (PD-L1). However, the efficacy of immunotherapy in PD-L1-negative urothelial carcinoma patients remains unclear, and biomarkers beyond PD-L1 expression to predict response to immunotherapy need investigation. Here, we report a metastatic renal pelvis urothelial carcinoma patient with PD-L1 negative expression that responded dramatically to first-line pembrolizumab plus lenvatinib. By the recent follow-up in March 2022, the patient had a complete radiological response for 3.4 years, with no recurrence even during the 23-month drug-withdrawal period. The results of the next-generation sequencing using the tumor sample revealed a high tumor mutational burden (TMB), which may be independently driven by the pathogenic mutation in TP53 , TERT , NCOR1 , and TSC2 genes. Besides, the tumor microenvironment exhibited an immune-active signature with relatively abundant CD8+ cells and M1 tumor-associated macrophages but scarce regulatory T cells may also explain the great benefit of the combination therapy. Our case provides a direction for identifying biomarkers beyond PD-L1 expression to screen urothelial carcinoma patients who benefit from ICI as well as ICI-based therapy.

Complete response to tislelizumab in a metastatic urothelial carcinoma after surgery associated with high tumor mutational burden: a case report.

Metastatic urothelial carcinoma (mUC) is associated with poor prognosis. Cisplatin-based combination chemotherapy is the preferred initial regimen for patients with mUC. However, a substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. Currently, immune checkpoint inhibitors (ICI) showed to be effective in cisplatin-ineligible mUC patients on first-line treatment. Tislelizumab is an anti-human programmed death receptor-1 monoclonal IgG4 antibody, which was specifically engineered to minimize binding to FcɣR on macrophages to abrogate antibody-dependent phagocytosis. But there is no report of tislelizumab as a first-line treatment for cisplatin-ineligible patients with mUC currently. Here, we report a cisplatin-ineligible mUC patient with PD-L1-negative, microsatellite stable (MSS), high tumor mutational burden (TMB-H) obtained complete response receiving tislelizumab therapy after laparoscopic debulking surgery. Progression-free survival has exceeded 16 months since treatment with tislelizumab. To our knowledge, this is the first reported case of cisplatin-ineligible mUC patient with PD-L1-negative, MSS and TMB-H who responded well to tislelizumab as a first-line treatment. However, we still need more studies to assess the efficacy of tislelizumab as a first-line treatment in cisplatin-ineligible mUC patients and to confirm predictive values of TMB for efficacy of tislelizumab.

Overexpression of miR-340 inhibits cell proliferation and induces apoptosis of human bladder cancer via targeting Glut-1.

BACKGROUND: Bladder cancer (BC) has high mortality due to distant metastasis. Previous works suggested that microRNA (miRNA)-340 is a critical regulator for the development and progression of various cancers. The specific biological function of miR-340 in BC is little known. METHODS: In the present study, RT-qPCR was performed to measure the expression of miR-340 in paired BC tissues and adjacent non-tumor tissues. Next, the target gene of miR-340 was identified using dual-luciferase reporter assay and its level was also tested in tissues. Moreover, cell proliferation and apoptosis were analyzed by CCK-8 and flow cytometry. Finally, the expression of PCNA, Bax was detected by RT-qPCR and western blotting, as well as PI3K/AKT signaling measured by western blotting. RESULT: The results demonstrated that miR-340 expression was downregulated and its target Glut-1 level was upregulated in BC tissues. Functionally, overexpression of miR-340 suppressed the proliferation and induced apoptosis in BC cells, while Glut-1 reversed the suppression of proliferation or induction of apoptosis induced by miR-340. Additionally, miR-340 repressed PCNA, p-PI3K and p-AKT levels but enhanced Bax level, while Glut-1 rescued the effects. CONCLUSION: In conclusion, miR-340 functions as a tumor suppressor of BC, which inhibited proliferation and induced apoptosis by targeting Glut-1 partly through regulating PCNA, Bax expression and PI3K/AKT pathway. This study suggested that miR-340 is a potential target for the treatment of BC.

A five-gene methylation signature predicts overall survival of patients with clear cell renal cell carcinoma.

BACKGROUND: In this study, we aimed to screen methylation signatures associated with the prognosis of patients with clear cell renal cell carcinoma (ccRCC). METHODS: Gene expression and methylation profiles of ccRCC patients were downloaded from publicly available databases, and differentially expressed genes (DEGs)-differentially methylated genes (DMGs) were obtained. Subsequently, gene set enrichment and transcription factor (TF) regulatory network analyses were performed. In addition, a prognostic model was constructed and the relationship between disease progression and immunity was analyzed. RESULTS: A total of 23 common DEGs-DMGs were analyzed, among which 14 DEGs-DMGs were obtained with a cutoff value of PCC < 0 and p < 0.05. The enrichment analysis showed that the 14 DEGs-DMGs were enriched in three GO terms and three KEGG pathways. In addition, a total of six TFs were shown to be associated with the 14 DEGs-DMGs, including RP58, SOX9, NF-κB65, ATF6, OCT, and IK2. A prognostic model using five optimized DEGs-DMGs which efficiently predicted survival was constructed and validated using the GSE105288 dataset. Additionally, four types of immune cells (NK cells, macrophages, neutrophils, and cancer-associated fibroblasts), as well as ESTIMATE, immune, and stromal scores were found to be significantly correlated with ccRCC progression (normal, primary, and metastasis) in addition to the five optimized DEGs-DMGs. CONCLUSION: A five-gene methylation signature with the predictive ability for ccRCC prognosis was investigated in this study, consisting of CCNB2, CDKN1C, CTSH, E2F2, and ERMP1. In addition, potential targets for methylation-mediated immunotherapy were highlighted.

Significance of preoperative systemic immune-inflammation (SII) in predicting postoperative systemic inflammatory response syndrome after percutaneous nephrolithotomy.

There is evidence that inflammation response biomarkers are positivity associated with bacteremia and urosepsis. The objective of this study was to investigate the value of preoperative systemic immune-inflammation (SII) in predicting systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL). Records from 365 consecutive patients who previously received standard PCNL for kidney stones were retrospectively reviewed. Exactly 108 (29.6%) of the 365 patients who underwent PCNL developed SIRS postoperatively. The association of SIRS with the preoperative risk factors of infectious complications was evaluated. Female gender, operating time, SII, neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR) were found to be independent predictors for post-PCNL SIRS. Female patients with SIRS were more likely to have positive urine culture, a higher level of serum leukocyte, and serum hs-CRP than male patients with SIRS. Receiver operating characteristic curve analysis indicated SII for predicting the occurrence of SIRS with a higher AUC (0.782) than other systemic inflammation biomarkers such as LMR (0.734), NLR (0.671), and PLR (0.617). As a novel integrated inflammation biomarker for predicting SIRS after PCNL, SII showed a better predictive value than other traditional inflammation indicators. To our knowledge, we present the first study to investigate the predictive value of the preoperative SII on post-PCNL SIRS.

Significant benefit of everolimus in a patient with urothelial bladder cancer harboring a rare M1043I mutation of PIK3CA.

Urothelial bladder cancer (UBC) is a common malignancy with considerable mortality worldwide. However, the treatment options of UBC are mainly chemotherapy and immunotherapy, as few targeted agents have demonstrated efficacy against UBC. In recent studies, everolimus has exhibited antitumor activity in patients harboring aberrations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway in multiple tumor types. Herein, we report the case of a patient with metastatic UBC harboring a rare M1043I mutation of PIK3CA which was detected using DNA-based next-generation sequencing. The patient received everolimus as first-line therapy after palliative transurethral resection. The treatment resulted in complete response within 1 month, and the patient achieved a progression-free survival (PFS) of >6 months according to reports from the last follow-up visit. To our knowledge, this is the first reported case of PIK3CA-mutant UBC for which everolimus therapy demonstrated a significant benefit suggesting that the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further insights into its mechanism and clinical studies are needed to clarify the effectiveness of everolimus therapy in patients with PIK3CA M1043I mutation.

Renal immature teratoma in a male adult: A case report and literature review.

RATIONALE: Teratomas commonly arise in the gonads, including ovary and testis. The kidney is one of the most rare regions of primary teratoma. To date, about 19 cases of renal teratoma have been reported, and only 3 articles have reported renal immature teratoma; however, all of them occur in infant or children. In the present study, we reported a renal inmature teratoma in a male adult. PATIENT CONCERNS: The present patient was a middle-aged man with aching pain in the left waist, and contrast-enhanced CT showed a lump in the left kidney with mild-to-moderate enhancement, and a low density small necrotic area was seen in the center. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: The patient underwent radical nephrectomy. Based on postsurgical histopathology, the final diagnosis of this case was renal immature teratoma. Postoperative chemotherapy was carried out, and the patient has been followed-up for 18 months without tumor recurrence. LESSONS: Adult renal immature teratoma is rare, and the diagnosis is mainly based on the pathological findings.

The prognostic value of microRNA-183 in human cancers: A meta-analysis.

BACKGROUND: Several studies have been conducted to explore the prognostic value of miR-183 in different types of cancer; however, their results were controversial. Therefore, the present meta-analysis was conducted to comprehensively evaluate the prognostic value of miR-183 expression level in cancer. METHODS: A comprehensive literature search was carried out by searching PubMed and EMBASE database between January 1966 and April 2017. Fixed effect and random effect models were used to evaluate the pooled hazard risk (HR) and the relevant 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also carried out. RESULTS: A total of 12 studies published between 2011 and 2017 were included in the present meta-analysis. The meta-analysis result indicated that there was a significant association between miR-183 expression level and overall survival (HR = 2.642; 95%CI: 2.152-3.245), and there was a significant association between miR-183 expression level and tumor progression (HR = 2.403; 95%CI: 1.267-4.559). In subgroup analysis, we found that high expression level was significantly associated with poor prognosis in most cancers (HR = 2.824, 95%CI: 2.092-3.813); however, low miR-183 level was significantly associated with poor prognosis in melanoma and pancreatic ductal adenocarcinoma (HR = 2.322, 95%CI: 1.337-4.031). CONCLUSIONS: The results of our meta-analysis indicated that the highly expressed miR-183 might predict poor survival of patients with most cancer types, whereas the downregulated miR-183 level might be associated with poor prognosis in patients with melanoma and pancreatic ductal adenocarcinoma.

Metformin therapy and prostate cancer risk: a meta-analysis of observational studies.

OBJECTIVE: Several observational studies have shown that metformin therapy may modify the risk of prostate cancer. We carried out a meta-analysis of relevant studies evaluating the effect of metformin therapy on prostate cancer risk. METHODS: We searched pubmed database (January 1966-February 2014) for case-control and cohort studies that assessed metformin therapy and prostate cancer risk. Two authors independently assessed eligibility and extracted data. Summary RRs was calculated using fixed-effects model or random-effects model. Heterogeneity among studies was examined using Q and I(2) statistics. RESULTS: We included six cohort studies and four case-control studies in the present meta-analysis, comprising 863,769 participants and 39,073 prostate cancer cases. The pooled RR of prostate cancer in relation to metformin therapy was 0.92 (95% CI: 0.84-1.02, P = 0.112). When we stratified the various studies by study type, we found that metformin therapy was associated with a significant reduced risk of prostate cancer among cohort studies (RR = 0.92, 95% CI [0.87, 0.96], P<0.001); however, no significant association was detected among case-control studies (RR = 0.95, 95% CI [0.78, 1.16], P = 0.632). There was also no indication of publication bias as suggested by Begg's test (P = 0.421) and Egger's test (P = 0.627). CONCLUSION: Our findings indicate that metformin therapy is not significantly associated with lower prostate cancer risk.

Vasectomy and the risk of prostate cancer: a meta-analysis of cohort studies.

BACKGROUND: The relationship of vasectomy to prostate cancer has great public health significance. However, the results of observational studies were conflicting. To determine whether vasectomy is associated with the risk of prostate cancer, we performed a meta-analysis of cohort studies. METHODS: A literature search was carried out using Pubmed, Embase, Cochrane Libraryl, and China National Knowledge Infrastructure (CNKI) between January 1966 and July 2013. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of nine cohort studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Pooled results indicated that vasectomy was not associated with a significant increase of total prostate cancer risk (RR = 1.07, 95% CI [0.79, 1.46]). When stratified the various studies by geographic location, we found a significant association between vasectomy and increased PCa risk among studies conducted in the USA (RR = 1.54, 95% CI [1.23, 1.93]), however, there was no significant association between vasectomy and PCa risk among studies conducted in non-USA countries (RR = 0.74, 95% CI [0.50, 1.09]). Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSIONS: In conclusion, the present meta-analysis of cohort studies suggested that vasectomy was not associated with increased risk of prostate cancer. More in-depth studies are warranted to report more detailed results, including stratified results by age at vasectomy, tumor grade, and tumor stage.

Robot-assisted versus laparoscopic partial nephrectomy for localized renal tumors: a meta-analysis.

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) is being performed more frequently for the minimally invasive management of localized renal tumors. However, it's unclear whether RAPN is more efficacious than the standard laparoscopic partial nephrectomy (LPN). The objective of this meta-analysis is to compare RAPN and LPN in terms of perioperative and oncologic outcomes for the treatment of localized renal tumors. METHODS: A systematic search of electronic databases including MEDLINE, EMBASE and OVID was conducted. Comparative studies comparing RAPN and LPN for the treatment of localized renal tumors were regarded eligible. The mean difference (MD), odds ratio (OR) and their corresponding 95% confidence intervals (CI) were calculated for each outcome. The methodologic quality of the included studies was evaluated using the strict criteria of the Newcastle-Ottawa scale. RESULTS: 14 comparative studies (n = 1539 participants) were included in the present meta-analysis. Operative time was similar for RAPN and LPN (MD = 6.33, 95% CI [-23.93, 36.59]), however, warm ischemia time favored RAPN (MD = -3.29, 95% CI [-6.47, -0.10]). There was no significant difference in estimated blood loss (EBL) (MD = -42.24, 95% CI [-87.10, 2.61]) and length of stay (LOS) (MD = -0.29, 95% CI [-0.89, 0.32]). The incidence of intraoperative complications was similar for RAPN and LPN (OR = 0.68, 95% CI [0.29, 1.58]), as well as incidence of postoperative minor complications (OR = 1.10, 95% CI [0.80, 1.51]) and postoperative major complications distributions by Clavien classification (OR = 0.99, 95% CI [0.61, 1.61]). In addition, no significant difference was found in terms of positive surgical margin rate (OR = 1.12, 95% CI [0.56, 2.25]). CONCLUSIONS: RAPN had similar operative time, LOS, EBL, and perioperative complications compared with LPN, as well as positive margin rates. RAPN appears to offer the advantage of decreased WIT compared with LPN. Studies with long-term follow up are needed to compare RAPN and LPN in terms of long-term complications and oncologic outcomes.