Prognostic Implications of Immune-Related Gene Pairs Signatures in Bladder Cancer.

Compelling evidence indicates that immune function is correlated with the prognosis of bladder cancer (BC). Here, we aimed to develop a clinically translatable immune-related gene pairs (IRGPs) prognostic signature to estimate the overall survival (OS) of bladder cancer. From the 251 prognostic-related IRGPs, 37 prognostic-related IRGPs were identified using LASSO regression. We identified IRGPs with the potential to be prognostic markers. The established risk scores divided BC patients into high and low risk score groups, and the survival analysis showed that risk score was related to OS in the TCGA-training set (p < 0.001; HR = 7.5 [5.3, 10]). ROC curve analysis showed that the AUC for the 1-year, 3-year, and 5-year follow-up was 0.820, 0.883, and 0.879, respectively. The model was verified in the TCGA-testing set and external dataset GSE13507. Multivariate analysis showed that risk score was an independent prognostic predictor in patients with BC. In addition, significant differences were found in gene mutations, copy number variations, and gene expression levels in patients with BC between the high and low risk score groups. Gene set enrichment analysis showed that, in the high-risk score group, multiple immune-related pathways were inhibited, and multiple mesenchymal phenotype-related pathways were activated. Immune infiltration analysis revealed that immune cells associated with poor prognosis of BC were upregulated in the high-risk score group, whereas immune cells associated with a better prognosis of BC were downregulated in the high-risk score group. Other immunoregulatory genes were also differentially expressed between high and low risk score groups. A 37 IRGPs-based risk score signature is presented in this study. This signature can efficiently classify BC patients into high and low risk score groups. This signature can be exploited to select high-risk BC patients for more targeted treatment.

LncRNA PlncRNA-1 accelerates the progression of prostate cancer by regulating PTEN/Akt axis.

Long non-coding RNAs are key regulators of tumor development and progression, with the potential to be biomarkers of tumors. This study aimed to explore the role of PlncRNA-1 in the progression of prostate cancer (PCa). We found that PlncRNA-1 was up-regulated in 85.29% of PCa tissues and could predict the T stage of PCa patients to a certain extent. Results showed that inhibition of PlncRNA-1 expression potentially promoted cell apoptosis, suppressed the proliferation, migration, and invasion of cells, and triggered G2/M cycle arrest in vitro and in vivo. PlncRNA-1 was mainly localized in the nucleus and PlncRNA-1 expression and phosphatase and tensin homologue (PTEN) expression were negatively correlated. Mechanistically, knockdown of PlncRNA-1 increased expression levels of PTEN protein and phosphorylated PTEN protein, and decreased expression levels of Akt protein and phosphorylated Akt protein. Rescue experiments demonstrated that PTEN inhibitors abolished the changes in PTEN/Akt pathway caused by PlncRNA-1 interference. PlncRNA-1 can promote the occurrence and development of PCa via the PTEN/Akt pathway. PlncRNA-1 may, therefore, be a new candidate target for the treatment of PCa.

The retrospective study of perioperative application of dexamethasone and furosemide for postoperative anti-inflammation in patients undergoing percutaneous nephrolithotomy.

OBJECTIVES: To investigate whether the perioperatively combined application of dexamethasone and furosemide could alleviate the inflammation in patients undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: 147 patients undergoing PCNL between November 2018 and October 2019 were enrolled in the study. 77 patients accepted a single dose of dexamethasone and furosemide administration (EXP group, n = 77), and 70 patients did not (CON group, n = 70). Demographic and perioperative data, inflammatory markers including interleukin-6 (IL-6) and procalcitonin (PCT), and clinical outcomes were compared between the two groups. RESULTS: Compared with the CON group, the incidence rate of urosepsis of the EXP group were significantly lower (11.69% vs. 24.29%, p = 0.046). 3 patients developed severe urosepsis in the EXP group, while 5 patients developed severe urosepsis in the CON group. Compared with those in the CON group, the patients with postoperative urosepsis in the EXP group showed lower serum levels of IL-6 at postoperative hour two (p = 0.045) and at postoperative day one (p = 0.031) and lower serum levels of PCT at postoperative day one (p = 0.015). There was a better clinical outcome of a shorter postoperative hospital stay (p = 0.015) in patients with postoperative urosepsis in the EXP group than in those in the CON group. CONCLUSION: The perioperatively combined application of dexamethasone and furosemide was beneficial for alleviating postoperative inflammatory reaction and caused a better clinical outcome of a shorter postoperative hospital stay.

The predictive and diagnostic ability of IL-6 for postoperative urosepsis in patients undergoing percutaneous nephrolithotomy.

The aim of this study is to investigate the predictive and diagnostic ability of interleukin-6 (IL-6) for postoperative urosepsis in patients undergoing percutaneous nephrolithotomy (PCNL). 90 patients undergoing PCNL between April 2019 and September 2019 were studied. 16 patients progressed to urosepsis (EXP1 group, n = 16) and 74 patients did not (CON group, n = 74); demographic and perioperative data were compared between these two groups. 25 patients who progressed to postoperative urosepsis without receiving the test of IL-6 between March 2018 and March 2019 were enrolled (EXP2 group, n = 25); demographic and perioperative data were compared between EXP1 group and EXP2 group. Compared with CON group, EXP1 group showed higher serum levels of IL-6 (p < 0.001) and neutrophil (p < 0.001) at postoperative hour two; higher serum levels of IL-6 (p < 0.001), procalcitonin (PCT) (p < 0.05), white blood cell (WBC) (p < 0.05), and neutrophil (p < 0.001) on postoperative day one; higher serum levels of PCT (p < 0.05) and WBC (p < 0.05) on postoperative day three. ROC curves showed IL-6 (AUC = 1.000) at postoperative hour two and PCT (AUC = 0.954) on postoperative day three. Compared with EXP2 group, EXP1 group showed shorter time to intervene (p < 0.001), a shorter postoperative hospital stay (p < 0.001), and a lower incidence rate of severe urosepsis (p < 0.05). There were different diagnostic abilities of IL-6, PCT, WBC, and neutrophil for postoperative urosepsis at different time points, and IL-6 was greatly valuable as a predictive and early diagnosing biomarker for postoperative urosepsis in patients undergoing PCNL at postoperative hour two and on postoperative day one.

Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis.

Apart from being potential prognostic biomarkers and therapeutic targets, long non-coding RNAs (lncRNAs) modulate the development and progression of multiple cancers. PlncRNA-1 is a newly discovered lncRNA that exhibits the above properties through multiple regulatory pathways. However, the clinical significance and molecular mechanisms of PlncRNA-1 in bladder cancer have not been established. PlncRNA-1 was found to be overexpressed in 71.43% of bladder cancer tissues. Moreover, the expression level correlated with tumor invasion, T stage, age, and number of tumors, but not with gender, recurrent status, preoperative treatment, pathological grade, and tumor size. The expression level of PlncRNA-1 can, to a certain extent, be used as a predictor of the degree of tumor invasion and T stage among BC patients. Inhibiting PlncRNA-1 expression impaired the proliferation, migration, and invasion of T24 and 5637 bladder cancer cells in vitro and in vivo. Specifically, PlncRNA-1 promoter in BC tissues was found to be hypomethylated at position 131 (36157603 on chromosome 21). PlncRNA-1 promoter hypomethylation induces the overexpression of PlncRNA-1. In addition, PlncRNA-1 modulated the expression of smad3 and has-miR-136-5p (miR-136). Conversely, miR-136 regulated the expression of PlncRNA-1 and smad3. PlncRNA-1 mimics competitive endogenous RNA (ceRNA) in its regulation of smad3 expression by binding miR-136. Rescue analysis further revealed that modulation of miR-136 could reverse the expression of smad3 and epithelial-mesenchymal transition (EMT) marker proteins impaired by PlncRNA-1. In summary, PlncRNA-1 has important clinical predictive values and is involved in the post-transcriptional regulation of smad3. The PlncRNA-1/miR-136/smad3 axis provides insights into the regulatory mechanism of BC, thus may serve as a potential therapeutic target and prognostic biomarker for cancer.

Should kidney volume be used as an indicator of surgical occasion for patients with autosomal dominant polycystic kidney disease?

To investigate the best surgical occasion of laparoscopic cyst decortications (LCDs) in patients with autosomal dominant polycystic kidney disease (ADPKD), in accordance with the renal volume (RV). We retrospectively analyzed 135 (65 male and 70 female) patients with ADPKD who underwent LCD between June 2011 and October 2015. Patients were divided into 4 groups according to the volume of the operated kidney measured from computed tomography scans: group A (28 patients, RV < 500 mL), group B (63 patients, RV = 500-1000 mL), group C (30 patients, RV = 1000-1500 mL), and group D (14 patients, RV > 1500 mL). We studied postoperative indicators at least 1-year follow-up. For each RV group, therapeutic responses of LCD in these patients with ADPKD were assessed by improvement of clinical parameters and manifestations. A significant glomerular filtration rate (GFR) improvement was found in RV group B (31.8 ±â€Š11.1 mL/min; final GFR 36.9 ±â€Š12.7 mL/min; P < 0.01), and RV group C (21.1 ±â€Š8.7 mL/min; final GFR 27.4 ±â€Š9.2 mL/min; P < 0.01). RV group C had much higher GFR improvements than did RV group B (P < 0.01). In addition, refractory pain in patients of RV groups B, C, and D was much relieved by LCD treatment. Compared with other RV groups, blood pressures in patients with ADPKD of RV group D were also improved (P < 0.01). Our study indicates that RV could be used to evaluate LCD clinical outcomes in patients with ADPKD. The results of LCD for patients with ADPKD with RV between 500 and 1500 mL were encouraging, especially with regards to renal function improvement and pain relief. Therefore, RV may become a useful marker to predict the timing of LCD surgery in patients with ADPKD.