Integrative analysis identifies AKAP8L as an immunological and prognostic biomarker of pan-cancer.

A-kinase anchoring protein 8L (AKAP8L) belong to the A-kinase anchoring protein (AKAP) family. Recent studies have proved that AKAP8L is associated with the progression of various tumors. To establish a more complete understanding of the significance of AKAP8L across various types of cancers, we conducted a detailed analysis of multiple histological datasets, including the level of gene expression in pancancer, biological function, molecular characteristics, as well as the diagnostic and prognostic value of AKAP8L in pancancer. Furthermore, we focused on renal clear cell carcinoma (KIRC), and of explored the correlation of AKAP8L with clinical characteristics, prognosis of distinct patient subsets, co-expression genes and differentially expressed genes (DEG). We also performed the immunohistochemical staining and semi-quantitative verification of the monoclonal antibody established by AKAP8L. Our findings indicate that AKAP8L expression varied significantly not only across most cancer types, but also across different cancer molecules and immune subtypes. In addition, the robust ability to accurately predict cancer and its strong correlation with the prognosis of cancer strongly suggest that AKAP8L may be a potential biomarker for cancer diagnosis and prognosis. Furthermore, the high expression levels of AKAP8L were related to the worse overall survival (OS), disease-specific survival (DSS) as well as progression-free interval (PFI) of KIRC with statistical significance, especially among distinct clinical subgroups of KIRC. To sum up, AKAP8L has the potential to serve as a critical molecular biomarker for the diagnosis and prognosis of pancancer, an independent prognostic risk factor of KIRC, and a novel molecular target for cancer therapies.

Comprehensive analysis reveals the value of the expression of chromobox family members for bladder urothelial carcinoma prognosis.

Bladder urothelial carcinoma (BLCA) accounts for 95% of all cases of bladder cancer worldwide, with a high incidence and poor prognosis. Chromobox (CBX) proteins play a key role in numerous malignant tumors; however, the role of CBX in BLCA remains unknown. Herein, the present study found that, compared with in normal bladder tissues, the expression levels of CBX1, CBX2, CBX3, CBX4 and CBX8 were markedly increased in BLCA tissues, as determined by Tumor Immune Estimation Resource, UALCAN and ONCOMINE analyses, whereas CBX6 and CBX7 were decreased in BLCA tissues. Furthermore, evident hypomethylation in the promoters of CBX1, and CBX2, as well as significant hypermethylation in the promoters of CBX5, CBX6 and CBX7, was detected in BLCA tissues compared with in normal bladder tissues. The expression of CBX1, CBX2 and CBX7 was involved in the prognosis of patients with BLCA. Low CBX7 expression was strongly associated with poorer overall survival in patients with BLCA, whereas high CBX1 and CBX2 expression was associated with poorer progression-free survival. Besides, significant associations were determined between the expression of CBXs and immune cell infiltration, including dendritic cells, neutrophils, macrophages, CD4+ T cells, CD8+ T cells and B cells. Overall, the current results may provide a rationale for developing new targets and prognostic markers for BLCA therapy.

Modified anterior approach preserving Retzius space versus standard anterior approach robot-assisted radical prostatectomy: A matched-pair analysis.

Objective: To compare our initial perioperative and postoperative outcomes of the modified anterior approach (MA) with Retzius space preservation robot-assisted radical prostatectomy (RARP) with the standard anterior approach (SA) RARP. Materials and methods: A retrospective analysis was performed on 116 patients with RARP completed by the same surgeon between September 2019 and March 2022. They were divided into SA-RARP group (77 cases) and MA-RARP group (39 cases). Propensity score matching was performed using eight preoperative variables, including age, BMI, preoperative PSA, biopsy Gleason score, prostate volume, D'Amico risk classification, SHIM, and clinical T stage. Functional outcome was assessed by urine pad count and SHIM after surgery, and oncological outcome was assessed by statistics of postoperative pathological findings as well as follow-up postoperative PSA. The median follow-up was 13 months and 17 months for MA-RARP and SA-RARP groups respectively. Results: Propensity score matching was performed 1:1, and baseline data were comparable between the two groups after matching. Comparison of postoperative data: MA-RARP group had less mean EBL than SA-RARP group (200 vs 150 ml, p = 0.033). PSM did not differ between groups (p = 1). In terms of urinary control recovery, the MA-RARP group showed significant advantages in urinary control recovery at 24 h, 2 weeks, 1 month and 3 months after catheter removal, respectively (48.6% vs 5.7%, p < 0.001; 80% vs 22.9%, p < 0.001; 94.3% vs 51.4%, p < 0.001; 100% vs 74.3%, p = 0.002). This advantage gradually disappeared 6 months or more after surgery. The median time to recovery of sexual function was shorter in the MA-RARP group (165 vs 255 d, p = 0.001). Conclusion: MA-RARP is safe and reliable, and can achieve better early urinary control function and sexual function recovery while achieving the primary tumor control goal.

Construction and validation of a prognostic model for predicting overall survival of primary adrenal malignant tumor patients: A population-based study with 1,080 patients.

Objective: Primary adrenal malignant tumor is rare. The factors affecting the prognosis remain poorly defined. This study targeted to construct and corroborate a model for predicting the overall survival of adrenal malignant tumor patients. Methods: We investigated the SEER database for patients with primary adrenal malignant tumor. 1,080 patients were divided into a construction cohort (n = 756) and a validation cohort (n = 324), randomly. The prognostic factors for overall survival were evaluated using univariate and multivariate Cox analyses. The nomogram was constructed and then validated with C-index, calibration curve, time-dependent ROC curve, and decision curve analysis in both cohorts. Then we divided the patients into 3 different risk groups according to the total points of the nomogram and analyzed their survival status by Kaplan-Meier curve with log-rank test. Results: The baseline characteristics of these two cohorts were not statistically different (P > 0.05). Using univariate and multivariate Cox analyses, 5 variables, including age, tumor size, histological type, tumor stage, and surgery of primary site, were distinguished as prognostic factors (P < 0.05). Based on these variables, we constructed a nomogram to predict the 3- year, 5- year, and 10-year overall survival. The C-indexes were 0.780 (0.760-0.800) in the construction cohort and 0.780 (0.751-0.809) in the validation cohort. In both cohorts, the AUC reached a fairly high level at all time points. The internal and external calibration curves and ROC analysis showed outstanding accuracy and discrimination. The decision curves indicated excellent clinical usefulness. The best cut-off values for the total points of the nomogram were 165.4 and 243.1, and the prognosis was significantly different for the three different risk groups (P < 0.001). Conclusion: We successfully constructed a model to predict the overall survival of primary adrenal malignant tumor patients. This model was validated to perform brilliantly internally and externally, which can assist us in individualized clinical management.

LncRNA GAS5 participates in the regulation of dexamethasone on androgen receptor -negative and -positive prostate cancer cell proliferation.

BACKGROUND: Androgen receptor (AR) and long non-coding RNAs (lncRNA) play important roles in the initiation and progression of prostate cancer (PCa). The present study was designed to investigate whether lncRNA growth arrest-specific 5 (GAS5) is involved in the regulation of dexamethasone on the proliferation of AR+ PCa and AR- PCa cell lines. METHODS: Cell proliferation and cell cycle distribution were assessed using MTT assay and flow cytometry, respectively. GAS5 expression was examined by quantitative real-time PCR. AR protein level was examined by Western blot. RNA immunoprecipitation and RNA pull-down were performed to analyze the binding of GAS5 to AR. RESULTS: In AR- PCa cell line PC3, dexamethasone upregulated GAS5 expression, induced cell cycle arrest in the G0/G1 phase and inhibited cell proliferation, which were enhanced by GAS5 overexpression and attenuated by GAS5 silencing. However, in AR+ PCa cell line 22Rv1, dexamethasone had no obvious effects on GAS5 expression, cell cycle distribution and cell proliferation. AR was localized in the cytoplasm and bound to GAS5, counteracting the proliferation-inhibitory effect of GAS5. CONCLUSION: Taken together, GAS5 participates in the regulation of dexamethasone on the proliferation of AR+ PCa and AR- PCa cell lines.

Intraoperative serious complications of laparoscopic urological surgeries: a single institute experience of 4, 380 procedures

ABSTRACT This study aimed to share a single institute experience of 4,380 procedures about in-traoperative serious complications of laparoscopic urological surgeries. From January 2005 to December 2013, 4,380 cases of laparoscopic urological surgeries were recruited in our department. The distribution, incidence, and characteristics of intraoperative serious complications were retrospectively sorted out and analyzed. The surgeries were divided into three groups: very difficult (VD), difficult (D), and easy (E). The com¬plication at Satava class II was defined to be serious. One hundred thirty one cases with intraoperative serious complications were found (3.0%). The incidence of these complications was significantly increased along with the difficulty of the surgeries (P<0.05). The highest morbidity of serious complication belonged to total cystectomy with a ratio of about 17% as compared with other surgeries (P<0.05). The types of these complications included small vascular injury demanding blood transfusion (101 cases, 77.1%), large vascular (venous and artery) injury (16 cases), hypercapnia & acidosis (8 cases), and organ injury (6 cases). The cases of conversion to open surgery were 37 (≤1%). There was no significant difference in the rates of conversion to open surgery among the three groups (P>0.05). The overall tendency of the intraoperative serious complications was decreasing with the time from 2005 to 2013. In conclusion, through standardized training including improving the surgical technique, being familiar with the anatomic relationship, and constantly summarizing the experience and lessons, laparoscopic surgery could be safe and effective with not only minimal invasion but also few complications.

Intraoperative serious complications of laparoscopic urological surgeries: a single institute experience of 4,380 procedures.

This study aimed to share a single institute experience of 4,380 procedures about intraoperative serious complications of laparoscopic urological surgeries. From January 2005 to December 2013, 4,380 cases of laparoscopic urological surgeries were recruited in our department. The distribution, incidence, and characteristics of intraoperative serious complications were retrospectively sorted out and analyzed. The surgeries were divided into three groups: very difficult (VD), difficult (D), and easy (E). The complication at Satava class II was defined to be serious. One hundred thirty one cases with intraoperative serious complications were found (3.0%). The incidence of these complications was significantly increased along with the difficulty of the surgeries (P<0.05). The highest morbidity of serious complication belonged to total cystectomy with a ratio of about 17% as compared with other surgeries (P<0.05). The types of these complications included small vascular injury demanding blood transfusion (101 cases, 77.1%), large vascular (venous and artery) injury (16 cases), hypercapnia & acidosis (8 cases), and organ injury (6 cases). The cases of conversion to open surgery were 37 (≤1%). There was no significant difference in the rates of conversion to open surgery among the three groups (P>0.05). The overall tendency of the intraoperative serious complications was decreasing with the time from 2005 to 2013. In conclusion, through standardized training including improving the surgical technique, being familiar with the anatomic relationship, and constantly summarizing the experience and lessons, laparoscopic surgery could be safe and effective with not only minimal invasion but also few complications.

Androgen Receptor Is Inactivated and Degraded in Bladder Cancer Cells by Phenyl Glucosamine via miR-449a Restoration.

BACKGROUND Bladder cancer caused by exposure to aniline dyes, chronic cystitis, and smoking is detected in approximately 70 000 new cases annually. In the USA alone, it leads to 15 000 deaths every year. In the present study, we investigated the role of 3-((4'-amino-[1,1'-biphenyl]-4-yl)amino)-4-bromo-5-oxo-2,5-dihydrofuran-2-yl acetate (ABDHFA) in the inhibition of bladder cancer cell viability. MATERIAL AND METHODS Viability of cells was examined using MTT assay and distribution of cell cycle was assessed by flow cytometry. Expression of cyclin D1, androgen, prostate-specific antigen (PSA), and miR-449a was analyzed using Western blot and quantitative real-time polymerase chain reaction assays. RESULTS The results demonstrated that ABDHFA treatment inhibited viability of UMUC3 and TCCSUP AR-positive bladder cancer cells. ABDHFA treatment led to break-down of AR in UMUC3 and TCCSUP cells after 48 h in a dose-dependent manner. Up-regulation of miR-449a by lentivirus transfection down-regulated the AR signalling pathway. In UMUC3 and TCCSUP cells, ABDHFA treatment led to inhibition of mRNA and protein expression corresponding to AR. CONCLUSIONS In summary, the present study demonstrates that proliferation of AR-positive bladder carcinoma cells is markedly reduced by ABDHFA treatment through arrest of cell cycle and degradation of AR protein. Thus, ABDHFA, a novel compound, can be used for the treatment of bladder cancer.

miR-20b promotes cellular proliferation and migration by directly regulating phosphatase and tensin homolog in prostate cancer.

MicroRNAs are small non-coding RNAs, which are critical regulators of carcinogenesis and tumor progression. Previous studies have identified that microRNA-20b (miR-20b) acts as an oncogene in numerous cancers. However, the role of miR-20b in prostate cancer remains unclear. The present study aimed to investigate the expression of miR-20b in prostate cancer and to examine whether modulating miR-20b expression impacts prostate cancer cellular proliferation and migration. It was revealed that miR-20b was strongly expressed in prostate cancer tissues compared with adjacent normal prostate tissues (P<0.05). Knockdown of miR-20b expression by miR-20b inhibitor inhibited VCaP and PC-3 cell growth and migration. Through bioinformatics analysis, phosphatase and tensin homolog (PTEN) was predicted as a target gene of miR-20b in prostate cancer cells, which was validated by dual-luciferase reporter assay and western blot analysis. In addition, restoration of PTEN expression levels did not affect endogenous miR-20b expression in prostate cancer cells. In conclusion, the present study indicated that miR-20b promotes cellular proliferation and migration by directly regulating PTEN in prostate cancer.

MicroRNA-223-3p inhibits human bladder cancer cell migration and invasion.

The regulation of initiation and progression during carcinogenesis of bladder carcinoma is not completely elucidated. Dysregulation of microRNAs has been detected to play critical roles in the development of various cancers, including bladder carcinoma, whereas the involvement of miR-223-3p in the tumorigenesis of bladder carcinoma has not been studied. Here, we show that significantly higher levels of nuclear receptor coactivator 1 and significantly lower levels of miR-223-3p were detected in bladder carcinoma tissue, compared to the adjacent non-tumor tissue. In addition, the levels of nuclear receptor coactivator 1 and miR-223-3p were inversely correlated. Moreover, low miR-223-3p levels in bladder carcinoma specimens were associated with poor prognosis. In vitro, depletion of miR-223-3p increased bladder carcinoma cell invasion, which was abolished by overexpression of nuclear receptor coactivator 1. Bioinformatics studies demonstrate that miR-223-3p may bind to the 3'-UTR of nuclear receptor coactivator 1 messenger RNA to inhibit its protein translation in bladder carcinoma cells. Together, our study highlights miR-223-3p as a previously unrecognized microRNA that inhibits bladder carcinoma invasiveness via nuclear receptor coactivator 1, and this finding may be important for developing innovative therapeutic targets in treating bladder carcinoma.

miR-5195-3p Inhibits Proliferation and Invasion of Human Bladder Cancer Cells by Directly Targeting Oncogene KLF5.

miRNAs play a key role in the carcinogenesis of many cancers, including bladder cancer. In the current study, the role of miR-5195-3p, a quite recently discovered and poorly studied miRNA, in the proliferation and invasion of human bladder cancer cells was investigated. Our data displayed that, compared with healthy volunteers (control) and SU-HUC-1 normal human bladder epithelial cells, miR-5195-3p was sharply downregulated in bladder cancer patients and five human bladder cancer cell lines. The oligo miR-5195-3p mimic or miR-5195-3p antagomir was subsequently transfected into both T24 and BIU-87 bladder cancer cell lines. The miR-5195-3p mimic robustly increased the miR-5195-3p expression level and distinctly reduced the proliferation and invasion of T24 and BIU-87 cells. In contrast, the miR-5195-3p antagomir had an opposite effect on miR-5195-3p expression, cell proliferation, and invasion. Our data from bioinformatic and luciferase reporter gene assays identified that miR-5195-3p targeted the mRNA 3'-UTR of Krüppel-like factor 5 (KLF5), which is a proven proto-oncogene in bladder cancer. miR-5195-3p sharply reduced KLF5 expression and suppressed the expression or activation of its several downstream genes that are kinases improving cell survival or promoting cell cycle regulators, including ERK1/2, VEGFA, and cyclin D1. In conclusion, miR-5195-3p suppressed proliferation and invasion of human bladder cancer cells via suppression of KLF5.

Retroperitoneal laparoscopic partial nephrectomy for treatment of metanephric adenoma (Report of 6 cases).

OBJECTIVES: To investigate the clinical and pathological features of metanephric adenoma (MA) and the clinical outcome after retroperitoneal laparoscopic nephron-sparing surgery. METHODS: Six out of 183 partial nephrectomies performed during January 2009 to August 2014 were confirmed to be MA confirmed by postoperative pathological study. Perioperative parameters of the six patients were then retrospectively collected, analyzed and compared with current literature, including warm ischemia time (WIT), total operation time, estimated blood loss (EBL), positive surgical margin (PSM), and complications. Surgical and oncological outcome of all six patients were evaluated based on a mean follow up of 17 months (5-48 months). RESULTS: Tumors in all six cases were all successfully removed by partial nephrectomy. Mean WIT was 24.7 min (19-35 min). Mean operation time was 103.6 min (82-147 min). Mean EBL was 53.5 ml (20-85 ml). No conversion, transfusion or other major complication were observed in all six cases. Postoperative pathology confirmed negative surgical margin in all six cases. During a mean of 17 month follow up (5-48 months), no local recurrence or metastasis were found in all six cases. CONCLUSION: MA is a rare benign primary kidney epithelial cancer, which could hardly be differentiated from renal malignancies based on preoperative imaging. Our data suggested that retroperitoneal laparoscopic partial nephrectomy can be used for surgical treatment of MA, in terms of tumor control and preservation of renal function.

[Correlation between the PTEN/MMAC1/TEP1 expression and cell proliferation and apoptosis in human renal cell carcinoma (RCC)].

BACKGROUND & OBJECTIVE: PTEN is a tumor suppressor gene with phosphatase activity. It had been proved the aberrant expression and mutation of PTEN in diverse types of human cancer; PTEN is closely associated with occurrence and development of malignant tumor. This study was conducted to investigate the expression of PTEN/MMAC1/TEP1 gene product in human renal cell carcinoma (RCC) and the correlation between the expression of PTEN and the biological behaviors of RCC. METHODS: The PTEN protein of 44 cases of RCC tissues confirmed by pathology after operation, 15 cases of adjacent normal renal tissues, and 10 cases of non-tumor normal renal tissues were assessed using immunohistochemical technique (SP). Fifteen RCC tissues and 10 normal renal tissues selected respectively from the renal tissues whose PTEN protein expression were positive as well as those from the negative were made to be the cell suspension mingled with paraffin. The proliferative index and the apoptosis incidence were examined by flow cytometry and the correlation between PTEN protein and the proliferation and apoptosis were analyzed. RESULTS: The expression of PTEN protein was mostly located in the renal cell plasma. The positive incidence of expression PTEN protein in RCC was 36.3% which was prominently lower than those in the adjacent normal tissues (77.3%) and the normal tissues (100.00%) (P< 0.01). There was no significant difference between the different sorts of tissues (P >0.05). The expression of PTEN in stage I, II is much higher than that in stage III, IV(P< 0.05). The proliferative index of RCC whose expression of PTEN protein was positive (5.6+/-0.8)% was significantly lower than that of negative (15.6+/-1.6)% (P< 0.01). While the apoptosis incidence was (6.5+/-1.9)%,which was much higher than that of RCC whose expression was (2.9+/-1.6)% (P< 0.01). CONCLUSION: The positive expression incidence of PTEN protein significantly decreases in RCC tissues. PTEN protein suppresses carcinoma by inducing the cell cycle to be blocked up in G1 phase and increasing the apoptosis incidence. The assessment of the expression PTEN protein is one of the important indexes of the development and prognosis of RCC.

[Localization diagnosis of chyluria by radionuclide lymphoscintigraphy].

OBJECTIVE: To study the effect of radionuclide lymphoscintigraphy, a new method of localization diagnosis of chyluria. METHODS: Radionuclide lymphoscintigraphy was used to examine 34 patients with chyluria and the results of radionuclide lymphoscintigraphy was compared with those of cystoscopy and lymphangiography. RESULTS: Among the 34 patients 85.3% of unilateral localization diagnosis by radionuclide lymphoscintigraphy was coincident with that by cystoscopy. The positive rate of bilateral localization diagnosis was higher than that by cystoscopy. CONCLUSION: A less invasive technique, radionuclide lymphoscintigraphy can be used as a new option for the localization diagnosis of chyluria.