A Prognostic Signature for Colon Adenocarcinoma Patients Based on m6A-Related lncRNAs.

N6-methyladenosine (m6A) modification is a common epigenetic modification. It is reported that lncRNA can be regulated by m6A modification. Previous studies have shown that lncRNAs associated with m6A regulation (m6A-lncRNAs) serve as ideal prognostic biomarkers. However, whether lncRNAs are involved in m6A modification in colon adenocarcinoma (COAD) needs further exploration. The objective of this study was to construct an m6A-lncRNAs-based signature for patients with COAD. We obtained the RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was employed to recognize lncRNAs associated with m6A regulation (m6A-lncRNAs). 24 prognostic m6A-lncRNAs was identified by univariate Cox regression analysis. Gene set enrichment analysis (GSAE) was used to investigate the potential cellular pathways and biological processes. We have also explored the relationship between immune infiltrate levels and m6A-lncRNAs. Then, a predictive signature based on the expression of 13 m6A-lncRNAs was constructed by the Lasso regression algorithm, including UBA6-AS1, AC139149.1, U91328.1, AC138207.5, AC025171.4, AC008760.1, ITGB1-DT, AP001619.1, AL391422.4, AC104532.2, ZEB1-AS1, AC156455.1, and AC104819.3. ROC curves and K M survival curves have shown that the risk score has a well-predictive ability. We also set up a quantitative nomogram on the basis of risk score and prognosis-related clinical characteristics. In summary, we have identified some m6A-lncRNAs that correlated with prognosis and tumor immune microenvironment in COAD. In addition, a potential alternative signature based on the expression of m6A-lncRNAs was provided for the management of COAD patients.

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml(-1).

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .

Continuous suture of a single absorbable suture: a new simplified vesicourethral anastomosis technique in laparoscopic radical prostatectomy.

The purpose of this study was to describe a new simplified technique for facilitating vesicourethral anastomosis in laparoscopic radical prostatectomy. After prostate removal, an approximately 15-cm-long absorbable suture with one three-eighths arc needle is passed from the outside in on the full thickness of the bladder neck at the 9 o'clock position and then from inside out on the full thickness of the urethra at the 9 o'clock position. It is knotted with the suture tail. Subsequently, a continuous suture is completed between the bladder neck and urethra. A 20-French silastic catheter is placed into the bladder before completing the anterior row of sutures. Three hundred twelve consecutive patients with localized prostate cancer who had undergone the new simplified vesicourethral anastomosis were included in this retrospective study. The average time of anastomosis was 10.5 minutes (range, 8-30 minutes), as recorded for an experienced laparoscopic surgeon. The incidence rate was 2.2% for urine leakage and 1.3% for bladder neck stenosis, and the continence rate was 86.9% at 1 month, 93.3% at 3 months, 98.1% at 6 months, and 98.7% at 1 year. We present a new simplified method for vesicourethral anastomosis. The method takes little operating time and is easy for novice laparoscopists to master. Moreover, this technique has low rates of urinary leakage and bladder neck stricture.

PIN1 promoter polymorphism (-842 G>C) contributes to a decreased risk of cancer: Evidence from meta-analysis.

Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene) regulates the conformation of proline-directed phosphorylation sites and is important in the etiology of cancer. Since the identification of a functional polymorphism of PIN1, (-842 G>C; rs2233678), in the PIN1 promoter region, numerous studies have evaluated the association between the PIN1 promoter polymorphism (-842 G>C) and cancer risk. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven previous case-control studies was performed, which included 4,524 cases exhibiting different tumor types and 4,561 control subjects. The published literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results of the present study demonstrated that individuals carrying the variant C allele (G/C and C/C) were associated with a significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62-0.90 for GC vs. GG; OR, 0.75; 95% CI, 0.64-0.88 for GC/CC vs. GG). In further stratified analyses, a decreased cancer risk was observed in the following subgroups: Breast and lung cancer patients, Asian individuals, and in studies with a sample size >500. The results indicated that the PIN1 promoter polymorphism (-842 G>C; rs2233678) contributes to a decreased risk of cancer via attenuating the transcriptional activity.

The role of mitochondrial aconitate (ACO2) in human sperm motility.

Deficiencies in tricarboxylic acid (TCA) cycle enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. In mammalian spermatozoa mitochondria, the TCA cycle is known to be a crucial metabolic pathway that contributes to produce ATP. There is little known about the role and mechanism of mitochondrial aconitase (ACO2), which is an important regulatory enzyme of the TCA cycle, in asthenozoospermia. In the current study, immunofluorescence staining localized ACO2 to the human sperm mid-piece. By immunoblotting, we demonstrated that the level of ACO2 protein in asthenozoospermic samples was significantly decreased compared with that in normal fertile men. Importantly, we first observed that co-incubation of isocitrate with low motile sperm suspensions significantly improved sperm motility, which might be due to elevated intracellular ATP. The improvement of the sperm motility by isocitrate may have important clinical implications in the treatment of asthenozoospermia and certainly warrants further investigation.

[Surgical treatment of penile Paget's disease: a report of 10 cases].

OBJECTIVE: To investigate the clinical characteristics and surgical treatment of penile Paget's disease. METHODS: We retrospectively analyzed the treatment and follow-up data of 10 cases of penile Paget's disease surgically treated in Jiangsu Provincial Government Hospital and Jiangsu Provincial People's Hospital from 2008 to 2012. RESULTS: All the 10 patients received expanded local resection of the lesion with reconstruction of the defects with scrotal skin flaps or free skin flaps from the thigh. All surgeries were successful and the postoperative course was uneventful with complete graft survival and no lymph node metastasis. IIEF scores obtained before and 1 -2 months after surgery showed no statistically significant differences in the penile erectile function (P = 0.229), sexual orgasm (P = 0.761), and sexual satisfaction (P = 0.801) of the patients. CONCLUSION: When penile skin lesions suggest the possibility of Paget's disease, biopsy should be performed and surgery should follow as soon as possible. The ideal surgical option is expanded local resection of the lesion with reconstruction of the defects with scrotal skin flaps or free flaps according to the patient's specific conditions.

Prognostic role of microRNA-221 in various human malignant neoplasms: a meta-analysis of 20 related studies.

BACKGROUND: MicroRNA-221 (miR-221) has been shown to play an important role in cancer prognosis. In order to evaluate the predictive value of miR-221, we compiled the evidence from 20 eligible studies to perform a meta-analysis. DESIGN: All of relevant studies were identified by searching PubMed, Embase, and Web of Science, and were assessed by further quality evaluation. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of total and stratified analyses, for overall survival (OS) and recurrence-free survival (RFS), were calculated to investigate the association between high miR-221 expression and cancer prognosis. RESULTS: We found that high miR-221 expression can predict a poor OS in malignant tumors (pooled HR = 1.55, P = 0.017) but has no significant association with RFS (pooled HR = 1.02, P = 0.942). Further in stratified analyses, high miR-221 expression was significantly associated with a poor OS in Asians (pooled HR = 2.04, P = 0.010) or serum/ plasma subgroup (pooled HR = 2.28, P<0.001), and even showed significantly poor OS (pooled HR = 1.80, P<0.001) and RFS (pooled HR = 2.43, P = 0.010) in hepatocellular carcinoma (HCC) subgroup, but was correlated to a favorable RFS in prostate cancer subgroup (pooled HR = 0.51, P = 0.004). CONCLUSIONS: Our findings demonstrate that miR-221 is more suitable to predict cancer prognosis in Asians, and it is a promising prognostic biomarker for HCC. The detection of miR-221 in serum or plasma samples may make it become an effective method for monitoring patients' prognosis and assessing therapeutic efficacy in the future.

[Adjuvant hormonal therapy immediately after radical surgery for high-risk organ-confined or locally advanced prostate cancer].

OBJECTIVE: To evaluate the effect of adjuvant hormonal therapy (AHT) immediately after radical surgery for high- risk organ-confined or locally advanced prostate cancer using the PSA-related biochemical relapse rate within 2 years after surgery. METHODS: We retrospectively analyzed 62 cases of high-risk organ-confined or locally advanced prostate cancer. The patients were treated by laparoscopic radical prostatectomy or radical retropubic prostatectomy after MRI and ECT systemic bone imaging examination, which revealed no regional lymph node or bone metastasis. Thirty-two of the patients (group A) received AHT orally or subcutaneously from 2 weeks to 1 months after operation, and another 30 (group B) were left untreated. We followed up the patients for 2 years, measuring the serum PSA level every 3 months, performing ECT every 6 months, and recording the adverse reactions, medication dura- tion, and the patients'quality of life. RESULTS: All the operations were successfully accomplished. The rate of 2-year biochemical relapse-free survival was 78.13% (25/32) in group A and 53.33% (16/30) in group B. CONCLUSION: AHT immediately after radical surgery can improve the rate of biochemical relapse-free survival of the patients with high-risk organ-confined or locally advanced prostate cancer and check the progression and metastasis of the disease.

[Testis-sparing surgery for benign testicular tumor].

OBJECTIVE: To investigate the safety and feasibility of testis-sparing surgery (TSS) in the treatment of testicular tumor. METHODS: We retrospectively analyzed the clinical data of 8 cases of benign testicular tumor treated by TSS in our hospital from October 2005 to March 2012. RESULTS: The 8 patients, aged 18-67 (mean 45) years, were preoperatively diagnosed with benign testicular tumor and all underwent partial testis resection. Rapid intraoperative pathology showed the incisal margins to be negative. Postoperative pathological examination confirmed Sertoli cell tumor in 3 cases, adenomatoid tumor in another 3, and mature teratoma in the other 2. The patients were followed up for 6 months to 7 years (mean 4 years), which revealed no relapse and metastasis, nor significant differences from the baseline in the testosterone level, IIEF score, and routine semen parameters. CONCLUSION: Testis-sparing surgery is one of the effective options for the management of benign testicular tumor, which can maximally preserve the testis tissue and protect the patient's sexual function.

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth.

The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen (PSA) level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRC was identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.

Application of the revised Tumour Node Metastasis (TNM) staging system of clear cell renal cell carcinoma in eastern China: advantages and limitations.

This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis (TNM) staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma (RCC) patients. A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled. All of the patients had pathologically confirmed clear cell RCC (ccRCC). All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review, and survival data were collected. Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival (CSS) and progression-free survival (PFS) after surgery. Continuous variables, such as age and tumour diameter, were calculated as mean values and standard deviations (s.d.) or as median values. Survival was calculated by the Kaplan-Meier method, and the log-rank test assessed differences between groups. Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system. Therefore, the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients. However, when using the revised 2010 staging system, we found that more than 92% of patients (288/313) with T3 tumours were staged in the T3a subgroup, and their survival data were not significantly different from those of patients with T2b tumours. In addition, T2 subclassification failed to independently predict survival in RCC patients.

Reconstruction of defects in 11 patients with penile Paget's diseases with split-thickness skin graft.

BACKGROUND: Extramammary Paget's disease (EMPD) is considered an intraepithelial adenocarcinoma. Paget's disease of the penis is the most common disease of EMPD in male patients. OBJECTIVE: The objective of this study was to investigate and improve our knowledge of the clinical features, diagnosis, therapeutic methods and outcome of penile Paget's disease. MATERIALS AND METHODS: Eleven patients from 2007 to 2012 with Paget's disease of the penis were analyzed retrospectively based on diagnosis, treatment and the results on follow-up. All patients received local expanding resection with intraoperative frozen sections and reconstruction of defects with split-thickness skin graft from autologous thigh tissue. RESULTS: All surgeries were successful, and the postoperative course was uneventful with complete wound healing and graft survival. No lymph node metastasis was obtained. Both the morphology of the penis and its function were well maintained. CONCLUSIONS: Chronic skin lesions of the penis should be biopsied as soon as possible, if they are suspected to be due to Paget's disease. Paget's disease of the penis should be treated with wide local excision and intraoperative frozen section examination. In addition, reconstruction of defects with split-thickness skin graft from the patient's thigh is an ideal choice for treatment.

Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population.

The hypoxia-inducible factor-1α (HIF-1α) plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIF1A (coding HIF-1α) have been shown to influence an individual's susceptibility to many human tumors; however, evidence on associations between HIF1A single-nucleotide polymorphisms (SNPs) and prostate cancer (PCa) risk is conflicting. We genotyped three potentially functional polymorphisms in HIF1A (rs11549465, rs11549467 and rs2057482) using the TaqMan method and assessed their associations with PCa risk in a case-control study of 662 PCa patients and 716 controls in a Chinese Han population. Compared with rs11549467 GG genotype, the variant genotypes GA+AA had a significantly increased PCa risk (adjusted odds ratio (OR)=1.70; 95% confidence interval (CI)=1.06-2.72), particularly among older patients (OR=2.01; 95%CI=1.05-3.86), smokers (OR=2.06; 95%CI=1.07-3.99), never drinkers (OR=2.16; 95%CI=1.20-3.86) and patients without a family history of cancer (OR=1.71; 95%CI=1.02-2.89). Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score (OR=2.14; 95%CI=1.22-3.75). No altered PCa risk was associated with the rs11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs11549467 were associated with increased PCa risk (OR=2.10; 95%CI=1.23-3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.

A modified method for the treatment of urethral fistula after hypospadias repair.

Urethrocutaneous fistula (UCF) is a common complication of hypospadias surgery for severe hypospadias. We report our experience in the management of UCF following hypospadias surgery with a prepuce-degloving method (PDM). Our study included 87 patients who developed UCF after hypospadias repair from May 2001 to December 2011. Either simple closure or PDM was performed to repair the fistula. In total, 61 patients underwent a simple closure or Y-V plasty of the fistula, and 26 underwent a PDM repair. The success rate was 78.7% for simple closure or Y-V plasty and 96.2% for PDM repair (P<0.05). PDM repair represents a good choice for UCF repair after hypospadias, and our high 96.2% success rate demonstrates its applicability.

[Glans-preserving surgery for superficial penile cancer].

OBJECTIVE: To investigate the safety and feasibility of glans-preserving surgery in the treatment of superficial penile cancer (SPCa). METHODS: We retrospectively analyzed the clinical data of 21 cases of SPCa treated by glans-preserving surgery in our hospital from January of 2003 to March of 2010. RESULTS: The study included 21 SPCa patients aged 36 to 57 (mean 46) years, with superficial lesions involving the glans penis, coronary sulcus or shaft skin. The tumors were staged and graded TaG1 in 6 cases, TaG2 in 5, TisG1 in 2, TisG2 in 4, T1G1 in 3, and T1G2 in 1. All the patients underwent glans-preserving surgery to preserve the normal appearance and functional integrity of the glans penis, and all returned to normal sexual activity 1 month after operation, with good sexual function and sexual satisfaction. Postoperative follow-up lasted 2 to 7 (mean 5) years, and 2 cases of recurrence in situ found at 6 and 9 months, respectively, which were successfully managed by a second glans-preserving surgery. CONCLUSION: Glans-preserving surgery is an effective method for superficial penile cancer. With proper selection of the patients, this procedure is technically safe, maximally preserves the penile appearance, and least affects the patients' sexual satisfaction.

Effect of surgical procedures on prostate tumor gene expression profiles.

Current surgical treatment of prostate cancer is typically accomplished by either open radical prostatectomy (ORP) or robotic-assisted laparoscopic radical prostatectomy (RALRP). Intra-operative procedural differences between the two surgical approaches may alter the molecular composition of resected surgical specimens, which are indispensable for molecular analysis and biomarker evaluation. The objective of this study is to investigate the effect of different surgical procedures on RNA quality and genome-wide expression signature. RNA integrity number (RIN) values were compared between total RNA samples extracted from consecutive LRP (n=11) and ORP (n=24) prostate specimens. Expression profiling was performed using the Agilent human whole-genome expression microarrays. Expression differences by surgical type were analyzed by Volcano plot analysis and gene ontology analysis. Quantitative reverse transcription (RT)-PCR was used for expression validation in an independent set of LRP (n=8) and ORP (n=8) samples. The LRP procedure did not compromise RNA integrity. Differential gene expression by surgery types was limited to a small subset of genes, the number of which was smaller than that expected by chance. Unexpectedly, this small subset of differentially expressed genes was enriched for those encoding transcription factors, oxygen transporters and other previously reported surgery-induced stress-response genes, and demonstrated unidirectional reduction in LRP specimens in comparison to ORP specimens. The effect of the LRP procedure on RNA quality and genome-wide transcript levels is negligible, supporting the suitability of LRP surgical specimens for routine molecular analysis. Blunted in vivo stress response in LRP specimens, likely mediated by CO(2) insufflation but not by longer ischemia time, is manifested in the reduced expression of stress-response genes in these specimens.

[Modified transperitoneal laparoscopic radical prostatectomy: technique and clinical outcomes].

OBJECTIVE: To evaluate the technique and clinical outcomes of modified transperitoneal laparoscopic radical prostatectomy. METHODS: A total of 105 patients received the operation with age ranging from 51 to 73 years from January 2008 to June 2010. Mean level of serum prostate specific antigen was 13.6 µg/L and mean prostatic volume was 45 ml. Pathological studies of biopsy confirmed the prostate carcinoma with Gleason score 6-8. Radionuclide bone scan revealed no metastasis. Based on previously retroperitoneal radical prostatectomy, modified technique was applied involving surgical approach, bladder neck dissection and vesicourethral anastomosis. RESULTS: Mean operative time was 93 min (65 - 150 min). Intraoperative blood loss was 115 ml (50 - 400 ml). No complication of bowl injury occurred. Positive surgical margin was present in 24 patients. Normal continence were seen in 64 patients after catheter removed. Recovery of incontinence within 3 months was seen in 33 patients and 3 to 12 months in 5 patients respectively. Three patients with incontinence were still in the follow-up. CONCLUSIONS: Transperitoneal laparoscopic radical prostatectomy provides large working space and clear anatomic exposure. Higher efficiency and lower complication rate are obtained through modified laparoscopic technique involving seminal vesicle isolation, bladder neck dissection and vesicourethral anastomosis.

[Expression of Bax and Bcl-2 gene in rat testis tissues induced by testicular denervation].

OBJECTIVE: To detect the changes of the expression of Bax and Bcl-2 gene in the denervated testis, and to explore the possible mechanisms underlying the apoptosis of germ cells induced by testicular denervation at the genetic translation level. METHODS: Eighteen mature SD rats (350-375 g) were equally divided into 3 groups: a sham operation group( SO) , a superior spermatic nerve group (SSN) and an inferior spermatic nerve group (ISN) , and the latter two received bilateral surgical removal of the superior spermatic nerve and the inferior spermatic nerve, respectively. The animals were killed I month after the operation. ISH SP-method was used to detect the expression of Bax and Bcl-2 protein. RESULTS: Significant up-regulation of Bax protein was detected in both the treatment groups 1 month after surgery( P <0. 05) , and the level of Bcl-2 protein remained unchanged. CONCLUSION: Bax gene is involved in the apoptosis of germ cells induced by testicular denervation.