Identifying the novel key genes in renal cell carcinoma by bioinformatics analysis and cell experiments.

BACKGROUND: Although major driver gene have been identified, the complex molecular heterogeneity of renal cell cancer (RCC) remains unclear. Therefore, more relevant genes need to be identified to explain the pathogenesis of renal cancer. METHODS: Microarray datasets GSE781, GSE6344, GSE53000 and GSE68417 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by employing GEO2R tool, and function enrichment analyses were performed by using DAVID. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Survival analysis was performed using GEPIA. Differential expression was verified in Oncomine. Cell experiments (cell viability assays, transwell migration and invasion assays, wound healing assay, flow cytometry) were utilized to verify the roles of the hub genes on the proliferation of kidney cancer cells (A498 and OSRC-2 cell lines). RESULTS: A total of 215 DEGs were identified from four datasets. Six hub gene (SUCLG1, PCK2, GLDC, SLC12A1, ATP1A1, PDHA1) were identified and the overall survival time of patients with RCC were significantly shorter. The expression levels of these six genes were significantly decreased in six RCC cell lines(A498, OSRC-2, 786- O, Caki-1, ACHN, 769-P) compared to 293t cell line. The expression level of both mRNA and protein of these genes were downregulated in RCC samples compared to those in paracancerous normal tissues. Cell viability assays showed that overexpressions of SUCLG1, PCK2, GLDC significantly decreased proliferation of RCC. Transwell migration, invasion, wound healing assay showed overexpression of three genes(SUCLG1, PCK2, GLDC) significantly inhibited the migration, invasion of RCC. Flow cytometry analysis showed that overexpression of three genes(SUCLG1, PCK2, GLDC) induced G1/S/G2 phase arrest of RCC cells. CONCLUSION: Based on our current findings, it is concluded that SUCLG1, PCK2, GLDC may serve as a potential prognostic marker of RCC.

Efficacy and safety of transurethral split of prostate for benign prostatic hyperplasia: a meta-analysis.

BACKGROUND: Transurethral resection of the prostate (TURP) is the first choice for the treatment of benign prostatic hyperplasia. However, Transurethral split of prostate (TUSP) also seems to have clear clinical efficacy and clinical promotion value. To better clarify the potential and limitations of this treatment of prostate hyperplasia. This study objectively evaluated the clinical efficacy and safety of TUSP. METHODS: The Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), Wanfang (Wanfang data), and SinoMed databases were searched for relevant studies. We then used Revman Manager 5.3 to perform a meta-analysis of all randomized controlled trials that evaluated the efficacy and safety of TUSP versus the classic surgical procedures commonly used in the clinic. RESULTS: A total of 7 studies involving 592 patients were included. The combined data showed that TUSP can shorten the operation time [MD: -33.68; 95% CI: - 38.45 to - 28.91; P < 0.001], reduce intraoperative blood loss [MD: -56.06; 95% CI: - 62.68 to - 49.43; P < 0.001], shorten the time of indwelling catheter [MD: -1.83; 95% CI: - 1.99 to - 1.67; P < 0.001], shorten the postoperative hospital stay length [MD: -1.61; 95% CI: - 1.90 to - 1.32; P < 0.001] and improved postoperative quality of life score (QOL) [MD: 0.16; 95% CI: 0.02 to 0.29; P = 0.02] compared to traditional surgical approaches. There were no statistically significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax), residual urine volume (RUV), or complications between TUSP and traditional approached. CONCLUSION: TUSP can be an effective alternative for clinical treatment of benign prostatic hyperplasia. Given the limitations of the included studies, more high-quality randomized controlled trials are needed in the future to validate or update the results of this analysis.

[Independent external verification of the nomograms for predicting lymph node metastasis in penile cancer].

Objective: To evaluate the two newly established nomograms for predicting lymph node metastasis in penile cancer based on the clinical data on a large cohort of patients. METHODS: We retrospectively studied the clinical data on 93 patients with penile cancer treated in the Center for Tumor Prevention and Treatment. Using the two recently established nomograms (Bhagat nomogram and Zhu nomogram), we predicted lymph node metastasis in the patients, analyzed the differences between prediction and the results of postoperative pathology, and compared the accuracy of prediction between the two nomograms with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: The median age of the patients was 55 (27－82) years. Positive lymph nodes were found in 31 cases (33.3%) postoperatively and in 9 (21.9%) of the 41 clinically negative cases. The AUC of the Bhagat nomogram was 0.739 and that of Zhu nomogram was 0.808, both of which were similar to the prediction accuracy of internal verification and manifested a medium predictive ability. CONCLUSIONS: The newly established Bhagat and Zhu nomograms can be used for predicting lymph node metastasis in penile cancer, but with a low precision, and therefore cannot be relied exclusively for the option of inguinal lymphadenectomy.

miR-186 downregulates protein phosphatase PPM1B in bladder cancer and mediates G1-S phase transition.

Nuclear factor-κB (NF-κB) is a core regulator in multiple tumorigenic pathways. Its activation is mediated by IκB kinase ß (IKKß). Protein phosphatase PPM1B is reported to dephosphorylate IKKß, thereby terminating IKKß-mediated NF-κB activation. However, the role of PPM1B in bladder cancer is unclear. The aim of this study was to determine the expression patterns and molecular mechanisms of PPM1B in bladder cancer. Comparative analyses were conducted in six bladder cancer cell lines, a normal urinary epithelial cell line, and adjacent non-tumorous bladder epithelia. Searches were conducted through publicly available algorithms and The Cancer Genome Atlas. HT-1376 and RT4 cells were transduced to stably overexpress PPM1B and its predicted regulator miR-186. Subsequent in vitro studies included 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation, anchorage-independent growth ability, luciferase reporter assays, and flow cytometric cell cycle analyses. A xenograft model was established in nude mice to evaluate the effect of PPM1B in bladder tumors in vivo. The results revealed that PPM1B was frequently downregulated in bladder cancer cells at both protein and messenger RNA (mRNA) levels, whereas miR-186 was upregulated. Further analyses showed that miR-186 promoted G1-S transition by targeting PPM1B at its 3'-untranslated region (3'UTR). Conversely, ectopic expression of PPM1B significantly suppressed proliferation and tumorigenicity in bladder cancer cells in vitro and in vivo, thereby neutralizing the oncogenic effect of miR-186. This study has identified PPM1B and miR-186 as potential diagnostic markers in bladder cancer. Promotion of PPM1B and suppression of miR-186 may offer effective therapeutic strategies in the treatment of bladder cancer.

Current Treatment for Low-Risk Prostate Cancer in China: A National Network Survey.

Objective: To analyze the current treatment for low-risk prostate cancer (LRPC) in China. Methods: A national questionnaire survey titled "A survey of current treatment of LRPC" was designed and released nationally through the network from July 16 to August 3, 2017. Results: A total of 1,116 valid questionnaires were recovered. The percentages of preferred treatment by active surveillance (AS) or radical prostatectomy (RP) were 29.21% and 45.61%, respectively. A correspondence analysis showed that the physician in charge was more inclined to choose AS than RP. Respondents from different institution types, hospitals with different annual numbers of newly admitted patients with prostate cancer, and with different familiarity with the LRPC definition presented a significant difference in the preferred treatments (p < 0.05). Urologists chose AS or not for the following reasons: tumor progression (52.51%), potential medical disputes (42.56%) (i.e., medical disputes from patients or their relatives when urologists choose AS to treat patients with LRPC and the patient has a poor outcome), fear of cancer (41.94%), and surgical risk (39.07%). These reasons were ubiquitous, and there was no significant difference among urologists for these concerns (p > 0.05). Personal skills, surgical risk, and tumor progression were the most common factors that influenced whether AS or RP was preferred (p < 0.05). Concern about the medical disputes brought about by AS was a key factor for not choosing AS (p < 0.05). Conclusions: LRPC is still dominated by RP in China, followed by AS. Personal skills, surgical risk, and concern about tumor progression were the common factors influencing whether AS or RP was preferred. In addition, medical disputes brought by AS are another key factor for not choosing AS. There will be more Chinese data in the future to guide treatment of LRPC.

Thyrotroph embryonic factor is downregulated in bladder cancer and suppresses proliferation and tumorigenesis via the AKT/FOXOs signalling pathway.

OBJECTIVES: Thyrotroph embryonic factor (TEF) plays an important role in several different processes in normal human cells; however, its function in malignant cells has not been fully elucidated. MATERIALS AND METHODS: The mRNA levels of TEF in 408 bladder cancer (BC) samples from the Cancer Genome Atlas (TCGA) database were analysed in depth. Next, the expression of TEF in 7 BC cell lines was compared to that in normal bladder epithelial cells. The cell count, colony formation and anchorage-independent growth assays as well as a nude mouse xenograft model were utilized to examine the effects of TEF on proliferation and tumorigenesis. Immunofluorescence staining, flow cytometry analysis and treatment with an AKT inhibitor were performed to explore the molecular regulation mechanisms of TEF in BC. RESULTS: Analysis of TCGA data indicated that TEF mRNA was decreased in BC samples compared to that in normal bladder epithelial cells and correlated with the poor survival of BC patients. Additional experiments verified that the mRNA and protein expression of TEF were significantly decreased in BC cells compared to that in normal bladder epithelial cells. Upregulation of TEF expression significantly retarded BC cell growth by inhibiting the G1/S transition via regulating AKT/FOXOs signalling. CONCLUSION: Our results suggest that TEF might play an important role in suppressing BC cells proliferation and tumorigenesis.

Upregulation of Holliday junction recognition protein predicts poor prognosis and biochemical recurrence in patients with prostate cancer.

Abnormal expression of Holliday junction recognition protein (HJURP) in several types of tumor cells plays a vital role in the formation and progression of tumors. Few studies have investigated the role of HJURP in prostate cancer (PCa). The aim of this study was to analyze the expression levels of HJURP in PCa and to establish the association with clinicopathological data. Reverse transcription quantitative polymerase chain reaction and immunohistochemical analysis were used to detect the expression levels of HJURP in benign and PCa prostate tissues. The Taylor dataset was statistically analyzed to determine if HJURP expression levels were associated with PCa clinicopathological data. HJURP was overexpressed in PCa tissues compared with benign prostate tissues. Statistical analysis of the Taylor dataset indicated that upregulation of HJURP was significantly associated with positive prostate-specific antigen (PSA) levels (P=0.004), high Gleason score (P=0.005), advanced pathological stage (P=0.007), metastasis (P<0.001) and PSA failure (P<0.001). Higher HJURP mRNA expression levels were significantly associated with shorter biochemical recurrence (BCR)-free survival (P<0.001). To the best of our knowledge, this study is the first report of HJURP upregulation in PCa tissues. Upregulation of HJURP may predict BCR-free survival and HJURP may be an oncogene that impacts the prognosis of patients with PCa.

MiR-200c inhibits bladder cancer progression by targeting lactate dehydrogenase A.

Lactate dehydrogenase A (LDHA) is overexpressed in various cancers. We investigated LDHA expression and function in bladder cancer. We demonstrate that LDHA is up-regulated in bladder cancer cells and promotes proliferation, invasion, and glycolysis. Additionally, we found that microRNA (miR)-200c directly targets LDHA in bladder cancer cells. Ectopic expression of miR-200c inhibited LDHA-induced glycolysis, cell proliferation, and invasion. Thus, targeting LDHA through miR-200c is a potential therapeutic strategy in bladder cancer.

[Therapeutic efficacy of bipolar plasmakinetic technique compared with transurethral resection on benign prostate hyperplasia].

OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with the bipolar plasmakinetic technique (PKRP) compared with the transurethral resection (TURP) in the treatment of benign prostate hyperplasia (BPH). METHOD: Four hundred BPH patients with matched lesions were divided into 2 groups: 200 patients, aged 74.1 (58-91), underwent transurethral prostatectomy with PKRP, and 200 patients, aged 73.8 (56-90), underwent TURP. RESULT: In the PKRP group the average IPSS decreased from 27.1 +/- 4.5 preoperatively to 11.3 +/- 3.4 postoperatively 6 months after (P < 0.01), the. average maximum flow-rate Q (max) increased from 6.1 +/- 2.4 ml/s preoperatively to 18.6 +/- 3.5 ml/s postoperatively (P < 0.01), and the average residual urine (RU) reduced from 102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). However in the TURP group the average IPSS decreased from 26.9 +/- 4.2 preoperatively to 10.8 +/- 3.6 6 months after the operation (P < 0.01), the Q (max) increased from 5.7 +/- 2.4 ml/s preoperatively to 19.1 +/- 3.7 ml/s postoperatively (P < 0.01), and the average RU decreased from 102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). There were no significant differences in these parameters between these 2 groups (all P > 0.05). The average catheter retention time was 31.5 h in the PKRP, significantly shorter than that in the TURP group (61.5 hours, P < 0.01). The incidence rate of post-operational asynodia in the PKRP group was 14.3%, not significantly different from that in the TURP group (15.2%, P > 0.05). During the operation no hemorrhage or transurethral resection syndrome (TURS) occurred in the PKRP group, however, there were 5 cases of TURS and 18 cases of blood transfusion in the TURP group. CONCLUSION: PKRP has the same therapeutic efficacy as TURP on BPH. Moreover, it was more cheaper and with lower complication than TURP.