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BACKGROUND: Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before. METHODS: In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. CIBERSORT algorithm was performed to assess the impact of these lncRNAs on the infiltration of immune cells. RESULTS: A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients’ overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune and autophagy related pathways were dramatically enriched in high-risk and low-risk groups, respectively, and lncRNAs related immune cells were identified by CIBERSORT. CONCLUSIONS: In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in immunomodulation.

Long non‐coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435‐2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435‐2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435‐2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up‐regulation of MIR4435‐2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435‐2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435‐2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435‐2HG on miR‐513a‐5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR‐513a‐5p. Finally, the rescue experiments revealed the relation among MIR4435‐2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435‐2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435‐2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.

Current targeted cancer therapies are largely guided by mutations of a single gene, which overlooks concurrent genomic alterations. Here, we show that RNASEH2B , RB1 , and BRCA2 , three closely located genes on chromosome 13q, are frequently deleted in prostate cancer individually or jointly. Loss of RNASEH2B confers cancer cells sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition due to impaired ribonucleotide excision repair and PARP trapping. When co-deleted with RB1 , however, cells lose their sensitivity, in part, through E2F1-induced BRCA2 expression, thereby enhancing homologous recombination repair capacity. Nevertheless, loss of BRCA2 resensitizes RNASEH2B/RB1 co-deleted cells to PARP inhibition. Our results may explain some of the disparate clinical results from PARP inhibition due to interaction between multiple genomic alterations and support a comprehensive genomic test to determine who may benefit from PARP inhibition. Last, we show that ATR inhibition can disrupt E2F1-induced BRCA2 expression and overcome PARP inhibitor resistance caused by RB1 loss.

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m6A RNA modification is a common abundant posttranscriptional modification of mRNAs occurring in cancer growth and progression. Accumulated evidence has proved that HNRNPC, which acts as a m6A reader, plays an essential role in the promotion of cancer occurrence and development; nevertheless, the role of HNRNPC in papillary renal cell carcinoma remained to be discovered. In this study, we comprehensively identified HNRNPC as a hub gene involved in m6A modification in pRCC. Then, the expression level, survival outcomes, PPI network, function enrichment, immune cell infiltration, and single-cell analysis were performed. Finally, we found that HNRNPC significantly promoted renal cell carcinoma proliferation and migration in vitro. In conclusion, our work proved that HNRNPC may act as a momentous m6A regulator, as well as a potential targetable biomarker for pRCC.

Current targeted cancer therapies are largely guided by mutations of a single gene, which overlooks concurrent genomic alterations. Here, we show that RNASEH2B, RB1, and BRCA2, three closely located genes on chromosome 13q, are frequently deleted in prostate cancer individually or jointly. Loss of RNASEH2B confers cancer cells sensitivity to poly(ADP–ribose) polymerase (PARP) inhibition due to impaired ribonucleotide excision repair and PARP trapping. When co-deleted with RB1, however, cells lose their sensitivity, in part, through E2F1-induced BRCA2 expression, thereby enhancing homologous recombination repair capacity. Nevertheless, loss of BRCA2 re-sensitizes RNASEH2B/RB1 co-deleted cells to PARP inhibition. Our results may explain some of the disparate clinical results from PARP inhibition due to interaction between multiple genomic alterations and support a comprehensive genomic testing to determine who may benefit from PARP inhibition. Finally, we show that ATR inhibition can disrupt E2F1-induced BRCA2 expression and overcome PARP inhibitor resistance caused by RB1 loss.

Objective To report our experience in the diagnosis, minimally invasive treatment, and composition of seminal vesicle calculi (SVC). Patients and methods In the present study, we evaluated 20 patients who were admitted to our hospital from January 2013 to January 2018. All the patients were diagnosed with intractable haematospermia and SVC. The diagnosis was further confirmed by seminal vesiculoscopy. SVC were removed by basket extraction; with larger SVC fragmented by holmium laser before extraction. Scanning electron microscopy, X-ray diffraction, and infrared spectroscopy were used to determine the SVC composition. Results All operations were completed successfully without surgical complications. SVC were mostly composed of hydroxyapatite and protein, suggesting that they were produced by infections. Conclusions Seminal vesiculoscopy is a simple, minimally invasive technique that can be used for diagnostic confirmation and treatment of seminal vesiculitis with SVC. This study improves our understanding of SVC and provides a theoretical basis for the prevention of postoperative recurrence of SVC.

BackgroundUbiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive.MethodsRCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism.ResultsWe identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications.ConclusionsOur findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies.

BackgroundCell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive role of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasis on immunity.MethodsThe RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated.ResultsOur results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P

Background Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity. Methods The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated. Results Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P Conclusions CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.

Additional file 1: Table S1: Clinical information of the 16 ccRCC patients.

Background: Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before.Methods: In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. Results: A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients' overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune-related pathways were dramatically enriched in high-risk patients according to GSEA. Conclusions: In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in Immunomodulation.

Patients who underwent laparoscopic partial nephrectomy from the First Affiliated Hospital of Nanjing Medical University from May 2016 to May 2019 were randomly divided into enhanced recovery after surgery (ERAS) and control groups. The clinical indicators, preoperative and postoperative anxiety, depression, and postoperative quality of life were compared between the two groups. The recovery time, hospitalization cost, incidence of complications, and postoperative anxiety of patients in the ERAS group were lower than those of the control group. The satisfaction during hospitalization, scores of physical function, role function, emotional function, and general health status of the ERAS group were also significantly increased. Applying the ERAS to patients undergoing laparoscopic partial nephrectomy can improve their prognosis, experience of medical treatment, and life quality after surgery as well as have certain economic advantages.

Renal tumor with inferior vena cava (IVC) tumor thrombus still remains one of the most medical challenges in urological oncology. Despite numerous researches reporting the surgical experiences and survivals of this kind of patients, there is still lacking a standard recommended therapy right now. We reported a case of metastatic renal cell carcinoma with Mayo III IVC tumor thrombus who underwent robotic-assisted complete removal of the intracaval thrombus and radical left nephrectomy followed by renal arterial chemoembolization and pazopanib administration. It provides a new scheme and mode of diagnosis and treatment for this kind of patients. The patient was a 50-year-old man with left low-back pain for 20 days diagnosed with left renal tumor and Mayo III IVC tumor thrombus at the earliest. Initially, the patient underwent the renal arterial chemoembolization and targeted treatment to inhibit tumor's progression. After a two-year therapy period, the size of renal mass and lung nodules decreased than before, as well as the IVC tumor thrombus dropped to level II. Considering the efficacy of previous treatments, we performed robot-assisted IVC thrombectomy and radical left nephrectomy for this patient. The post-operative pathological examination confirmed the diagnosis of tumor thrombus as renal clear cell carcinoma. The patients recovered well after surgery and was followed-up for 36 months during the whole treatment course. This case with metastatic renal cell carcinoma (mRCC) and Mayo III IVC tumor thrombus received the interventional therapy, molecular targeted therapy and robot-assisted surgery successively, and acquired satisfying outcome. Patients with mRCC always suffer shorter overall survivals and aggressive progression compared with those localized tumors, therefore it is essential to formulate rational comprehensive treatment and carry out in time following-up.

BACKGROUND: Previous studies have investigated magnetic resonance imaging-targeted biopsy (MRI-TBx) on the detection for prostate cancer (PCa). Prostate Imaging Reporting and Data System (PI-RADS), as a standardized MRI reporting system, has widely been used in the management of PCa. However, basing the PI-RADS score, the comparability between MRI-TBx and transrectal ultrasound-guided biopsy (TRUS-Bx) in diagnosing PCa remained inconsistent or even controversial. Thus, this systematic meta-analysis aimed to assess the value of PI-RADS in sifting better prostate biopsy method. METHODS: A meta-analysis including 10 articles was performed. In these included studies, biopsy-naive subjects with concerning PSA levels and/or an abnormal digital rectal examination (DRE) were consecutively enrolled by referral from urologists. All subjects underwent multiparameter MRI (mpMRI) prostate and the results were scored independently by PI-RADS. Subjects with equivocal (PI-RADS 3) and intermediate/high-risk (PI-RADS 4/5) lesions underwent MRI-TBx and followed by TRUS-Bx performed by a urologist. The online databases PubMed, Embase and Web of Science were searched to find all correlated articles until October 1(st), 2019. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the associations. Subgroup analyses were conducted based on Gleason score. RESULTS: Overall, 10 studies were included in this meta-analysis from January, 2015 to June, 2019. In the comparison of the detection of MRI-TBx and TRUS-Bx in PCa patients, TRUS-Bx had a significant advantage in overall PCa detection compared with MRI-TBx (OR =0.78, 95% CI: 0.62–0.98) in PI-RADS 3. Basing subgroup analysis of Gleason score (csPCa: Gleason score ≥7; non-csPCa: Gleason score

Primary Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the kidney represents a spectrum of rare neoplasm with dismal clinical prognosis. This type of malignant tumor predominantly occurs in the soft tissue and bones of pediatric-young adults, and it may rarely arise from the kidney. Derived from the neuroectoderm, renal ES/PNET belongs to a group of primitive and aggressive tumors in its biological manifestation. Herein, we report the case of a 40-year-old pregnant woman with renal mass, in whom was found gross hematuria and slight lumbar acid during pregnancy. A computed tomography scan revealed an irregular soft tissue mass approximately 5×5×5 cm in size. The patient underwent robot-assisted laparoscopic nephrectomy of the right kidney after childbirth. The diagnosis of renal ES/PNET was confirmed by immunohistochemical detection and fluorescence in situ hybridization of the nephrectomy specimen. Primary renal ES/PNET represents a rare and lethal entity, especially in a 40-year-old pregnant woman. Although the clinical presentation of this tumor is nonspecific, renal ES/PNET frequently exert dismal prognosis and aggressive clinical outcomes. Thus, it is essential to distinguish ES/PNET from other renal cell carcinomas and carry out an optimum treatment strategy as soon as possible.

Tetraspanin CD151 has been identified as a tumor promoter, which is upregulated in various malignant cell types. However, the function of CD151 and its underlying mechanism in renal cell carcinoma is still unknown. In this study, we detected the expression of CD151 in RCC cells and tissues and explored its regulatory mechanism. We found that CD151 was upregulated in renal cell carcinoma tissues and cells and its expression was significantly associated with tumor stage (p=0.019) and survival (p=0.001) by analyzing tissue microarrays. After silencing of CD151 via lentivirus vector in Caki-1 and Caki-2 cells, reduced ability of migration and invasion were detected with downregulation of CD151. The opposite results were observed in cells with CD151 overexpression. Furthermore, western blotting was performed to investigate the influence of CD151 on epithelial-to-mesenchymal transition, matrix metalloproteinase 9 and TGF-β1/Smad signaling pathway in RCC. Subsequently, upregulating the protein level of transforming growth factor-β1 in cells with silencing of CD151 could rescue the malignant behaviors inhibited, which indicated that CD151 may play its promoting role in RCC partially by stimulating the expression of TGF-β1. Conclusively, CD151 might exhibit a prominent role in migration and invasion of RCC cells via activating TGF-β1/Smad signaling pathway.

Jundong Zhu,* Chenkui Miao,* Shouyong Liu,* Ye Tian, Chao Zhang, Chao Liang, Aiming Xu, Qiang Cao, Zengjun Wang Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China *These authors contributed equally tothis work Abstract: Tetraspanin CD82, also known as KAI1, was revealed as an attractive prognostic tumor biomarker in recent studies. However, some results of these studies remained debatable and inconclusive. Therefore, we conducted a meta-analysis to clarify the precise predictive value of CD82 in various neoplasms. Qualified studies were identified up to April 27, 2017, by searching PubMed, EMBASE, and the Web of Science. In total, 29 eligible studies were ultimately enrolled in this meta-analysis. Pooled hazard ratios (HRs) with 95% CIs of overall survival and disease/recurrence/progression-free survival were calculated to evaluate the correct prognostic role of CD82. Statistical analysis demonstrated that high expression of CD82 was significantly associated with enhanced overall survival (HR=0.56, 95% CI: 0.47–0.67) and disease/recurrence/progression-free survival (HR=0.42, 95% CI: 0.30–0.59) in cancer patients. Furthermore, we also conducted the subgroup analysis and the results revealed that CD82 was associated with favorable outcomes in cancer patients. Taken together, CD82 could be a promising biomarker for predicting the prognosis of patients with malignant neoplasms, and the biological functions of CD82 are of great research value of the subject. Keywords: CD82, KAI1, prognosis, meta-analysis

// Chao Liang 1, * , Huiyu Dong 1, * , Chenkui Miao 1, * , Jundong Zhu 1 , Jie Wang 1 , Pu Li 1 , Jie Li 1 and Zengjun Wang 1 1 State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Zengjun Wang, email: zengjunwang@njmu.edu.cn Jie Li, email: drc_lijie@126.com Keywords: TRIM29; prognosis; meta-analysis; malignant neoplasm Received: July 21, 2017 Accepted: October 28, 2017 Published: December 22, 2017 ABSTRACT Recent studies have shown that tripartite motif-containing protein 29 (TRIM29) had prognostic values in several cancers. However, different studies have been inconsistent. We conducted a meta-analysis to elucidate the precise predictive value of TRIM29 in various human malignant disease. Eleven eligible studies with 2046 patients were ultimately enrolled in this meta-analysis. Heterogeneity between studies was assessed using I 2 statistics. Pooled Hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease recurrence were calculated to investigate the correlation between TRIM29 expression and cancer prognosis. The results identified an important link between upregulated TRIM29 expression and poor prognosis in patients with multiple human malignant neoplasms in terms of recurrence-free survival (RFS)/disease-free survival (DFS) (HR = 1.66, 95% CI 1.36–2.04) but favorable progression-free survival (PFS)/metastasis-free survival (MFS) (HR = 0.37, 95% CI 0.16–0.85). We found that high TRIM29 expression predicted no significant impact on overall survival (OS) (HR = 1.32, 95% CI 0.90–1.93). Subgroup analyses showed that high TRIM29 expression predicted poor OS in Asians (HR = 2.21, 95% CI 1.78–2.74) but favorable OS in Caucasian (HR = 0.47, 95% CI 0.25–0.89). TRIM29 might play an essential role in carcinogenesis of multiple human malignant neoplasms and could serve as a biomarker for the prediction of patients’ prognosis.

// Chenkui Miao 1, * , Jingyi Cao 2, * , Yuhao Wang 1, * , Bianjiang Liu 1 and Zengjun Wang 1 1 State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Department of Urology, Xuzhou Cancer Hospital, Xuzhou, China * These authors contributed equally to this work Correspondence to: Bianjiang Liu, email: bjliu@njmu.edu.cn Zengjun Wang, email: zengjunwang@njmu.edu.cn Keywords: VEGF/VEGFR, polymorphisms, metastatic renal cell carcinoma, sunitinib, meta-analysis Received: July 11, 2017 Accepted: July 26, 2017 Published: August 04, 2017 ABSTRACT To summarize and clarify the association between vascular endothelial growth factor ( VEGF ) and vascular endothelial growth factor receptor ( VEGFR ) polymorphisms and the outcome in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. A total of 8 studies including 900 patients were analyzed in this systematic review after screening the database of PubMed, EMBASE and Web of Science. Hazard ratios (HRs) with 95% confidence interval (CI) were used to evaluate the strength of the association. VEGFR1 rs9582036 AA/AC carriers and rs9554320 CC/AC carriers had more favorable overall survival (OS) in patients with mRCC treated with sunitinib ( n = 3), but not in progression-free survival (PFS). In addition, VEGFA rs2010963 was associated with poorer PFS of mRCC ( n = 1). VEGFA rs699947 was significant in predicting PFS by univariate analysis, but showed no statistical significance in OS ( n = 1). VEGFR2 rs1870377 was verified to be associated with sunitinib OS ( n = 1). Furthermore, patients with VEGFR3 rs307826 and rs307821 had shorter PFS and OS during sunitinib therapy ( n = 2, respectively). Our results suggested that VEGF and VEGFR polymorphisms were associated with outcomes in sunitinib treated mRCC patients, especially VEGFR1 polymorphisms. However, considering the limited study numbers, its clinical application in sunitinib treated mRCC still needs further confirmation.

// Jundong Zhu 1, * , Chao Liang 1, * , Yibo Hua 1, * , Chenkui Miao 1 , Jianzhong Zhang 1 , Aiming Xu 1 , Kai Zhao 1 , Shouyong Liu 1 , Ye Tian 1 , Huiyu Dong 1 , Chao Zhang 1 , Pu Li 1 , Shifeng Su 1 , Chao Qin 1 and Zengjun Wang 1 1 Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Zengjun Wang, email: zengjunwang@njmu.edu.cn Chao Qin, email: 13776678978@163.com Keywords: CD82/KAI1, tetraspanin, migration/invasion, TGF-β1/Smad signaling, renal cell carcinoma Received: March 28, 2017 Accepted: April 19, 2017 Published: May 23, 2017 ABSTRACT The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in various malignant cell types. However, the function of CD82 and its underlying anti-metastasis role in renal cell carcinoma (RCC) is still unraveled. Here, we investigated the expression of CD82 in RCC and explored its regulatory mechanism in RCC cell lines. We found that CD82 was down-regulated in RCC tissues and cells and its expression was significantly associated with histological grade(p=0.041), tumour stage (p=0.036) and tumor size(p=0.020) by analyzing tissue microarrays. After upregulation of CD82 through lentivirus, reduced ability of migration and invasion in Caki-1 cells were detected. In contrast, gene silencing of CD82 by small interfering RNA promoted metastatic and invasive potential of 786-O cells. Furthermore, Western blot was performed to identify the influence of CD82 on MMP family and TGF-β1/Smad pathway in RCC. Subsequently, upregulating protein level of TGF-β1 with the overexpression of CD82 could rescue the malignant behaviors inhibited by CD82 which indicated that CD82 played its inhibitory role in RCC partially by attenuating the expression of TGF-β1. Taken together, CD82 played a prominent role in migration and invasion of RCC cells and it might exhibit its inhibitory role in RCC metastasis via block TGF-β1/Smad signaling pathway.

// Chenkui Miao 1, * , Jianzhong Zhang 1, * , Kai Zhao 1, * , Chao Liang 1, * , Aiming Xu 1 , Jundong Zhu 1 , Yuhao Wang 1 , Yibo Hua 1 , Ye Tian 1 , Shouyong Liu 1 , Chao Zhang 1 , Chao Qin 1 and Zengjun Wang 1 1 State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Zengjun Wang, email: zengjunwang@njmu.edu.cn Chao Qin, email: 13776678978@163.com Keywords: miR-148/152 family, human malignancies, prognosis, meta-analysis Received: March 14, 2017 Accepted: April 07, 2017 Published: May 17, 2017 ABSTRACT Recent studies have demonstrated that microRNA-148/152 family emerges as a attractive biomarker for predicting tumor prognosis and progression. However, outcomes of different studies are controversial. Eligible Literature were searched through online databases: PubMed, EMBASE and Web of Science. A total of 24 eligible studies were ultimately enrolled in this meta-analysis. Results indicated that overexpression of miR-148/152 family was significantly correlated with enhanced overall/cause-specific survival (OS/CSS) (HR=0.63, 95% CI: 0.54-0.74). Stratified analysis indicated that high miR-148a and miR-148b expression predicted favorable OS/CSS (HR=0.76; 95% CI: 0.69-0.90) and (HR=0.49; 95% CI: 0.39-0.61), while miR-152 developed no significant impact (HR=0.40, 95% CI: 0.12-1.29). MiR-148/152 family was distinctly associated with superior OS/CSS in Asian (HR=0.53, 95% CI: 0.44-0.64), but not in Caucasian (HR=0.96, 95% CI: 0.82-1.13). Futhermore, miR-148/152 family expression also predicted longer disease/relapse/progression-free survival (DFS/RFS/PFS) (HR=0.37, 95% CI: 0.16-0.88). A significantly favorable DFS/RFS/PFS was observed in Asian (HR=0.21, 95% CI: 0.06-0.81) than that in Caucasian (HR=0.76, 95% CI: 0.31-1.87). miR-148/152 family overexpression also predicted longer DFS/RFS/PFS in tissues (HR=0.11, 95% CI: 0.01-0.98), but not in plasma/serum (HR=0.67, 95% CI: 0.38-1.18). Our meta-analysis demonstrated that overexpression of miR-148/152 predicted enhanced OS/CSS and DFS/RFS/PFS of cancer patients. MiR-148a/b family may serve as a potential prognostic factor in multiple human malignancies.

// Chenkui Miao 1,* , Chao Liang 1,* , Jundong Zhu 1,* , Aiming Xu 1 , Kai Zhao 1 , Yibo Hua 1 , Jianzhong Zhang 1 , Wei Chen 2 , Chuanjian Suo 1 , Chao Zhang 1 , Yiyang Liu 1 , Shifeng Su 1 and Zengjun Wang 1 1 State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China 2 Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Zengjun Wang, email: // Shifeng Su, email: // Keywords : matrix metalloproteinases, bladder cancer, prognosis, meta-analysis Received : September 06, 2016 Accepted : February 21, 2017 Published : March 04, 2017 Abstract Recent studies have shown that matrix metalloproteinases (MMPs) might be a biomarker for predicting outcomes of bladder cancer. However, the prognostic value of overexpression of MMPs in bladder cancer is debatable and the studies are inconsistent. Therefore, this meta-analysis was performed to clarify the specific association and prognostic value of overexpression of MMPs in bladder carcinoma. Relevant studies were identified by searching PubMed, EMBASE, and the Web of Science. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for disease-specific survival (DSS), overall survival (OS), disease/recurrence-free survival (DFS/RFS), and progression/metastasis-free survival (PFS/MFS) were analyzed to determine the prognostic value of MMPs. In total, eighteen applicable studies were included in this meta-analysis. We found that high expression of MMPs significantly correlated with a poor DSS and OS (HR=1.66; 95% CI = 1.38–2.01 and HR= 1.67; 95%CI= 1.26–2.22). MMPs also predicted tumor progression and metastasis with a pooled HR of 3.03 (95% CI 1.98–4.64). However, high MMPs expression had no pivotal impact on DFS/RFS (HR= 1.21; 95% CI= 0.96–1.53). With the purpose of better understanding the prognostic role of MMPs in patients wirh bladder carcinoma, we carried out this systematic review and meta-analysis.

Renal ischemia-reperfusion (I/R) injury is inevitable in partial nephrectomy and other kidney surgeries, with a higher incidence in patients with renal insufficiency. This study aimed to investigate the protective effects of precise segmental renal artery clamping (SRAC) against renal I/R injury in db/db diabetic mice, compared with conventional renal artery clamping (RAC). Grape seed extract, a powerful free radical scavenger, was administered to diabetic mice for 4 weeks before operation in subgroups (30 mg/kg/d). The unilateral renal pedicle was ligatured, and I/R injury to the contralateral kidney was induced (ischemia for 30 min followed by reperfusion for 24 h). Blood glucose value, creatinine, blood urea nitrogen, and urine microalbumin/urine creatinine ratio increased gradually and showed no preoperative statistical differences among six subgroups. These parameters were significantly lower in the SRAC than in the RAC group 24 h postoperatively. Moreover, the nonischemic area in the SRAC group expressed less KIM-1 and TNF-αmRNA and also revealed minor histopathological damage induced by I/R. These findings suggest that SRAC effectively reduces early renal injury induced by I/R and accelerates the recovery of renal function in diabetic mice. Thus, SRAC may be an ideal technique in partial nephrectomy, especially for patients with diabetic nephropathy and other renal insufficiencies.

The mRNA expression of CAPN2 was upregulated in CRPC cells (DU145 and PC3) than that in non-CRPC cells. Silencing CAPN2 expression could inhibit DU145 and PC3 cells proliferation by cell cycle arrest at G1 phase. Knockdown of CPAN2 level suppressed the migration and invasion capacity of CRPC cells by reducing matrix metalloproteinase-2 (MMP-2) and MMP-9 activation, as well as repressing the phosphorylation protein expression of AKT and mTOR. In addition, we found that the expression of CAPN2 was elevated in Pca tissues than that in normal control tissues. Therefore, we showed the important roles of CAPN2 in the development and progression in CRPC cells, suggesting a new therapeutic intervention for treating castration-resistant prostate cancer patients.

Growing evidence indicates that aberrant expression of microRNAs (miRNAs) contributes to tumorigenesis in various human malignancies. In this study we revealed that miR-195 acted as a tumor suppressor in renal cell carcinoma (RCC) through inhibition of HMGA1 expression. qRT-PCR was used to detect the miR-195 expression in RCC tissues and cell lines. RCC cell line Caki-1 and Caki-2 cells were used in this study. The luciferase report assay and rescue assay were performed to identify HMGA1 as the target gene of miR-195. Additionally, Kaplan-Meier method and log-rank test was used to explore the relationship between HMGA1 expression and RCC prognosis. We observed that miR-195 expression was significantly downregulated both in RCC tissues and in RCC cell lines. We observed that miR-195 overexpression inhibits the abilities of RCC cell proliferation, cell cycle progression and metastasis in vitro by targeting HMGA1 via epithelial to mesenchymal transition (EMT) pathway. In clinical specimens, HMGA1 was overexpressed in high-grade RCC when compared with its levels in normal tissues and low-grade RCC cancer, its expression levels were inversely correlated with overall survival. Our findings highlight an important role of miR-195 and HMGA1 in the molecular etiology of RCC, indicating that they can serve as potential biomarkers and therapy targets of RCC.

Background The mammalian homologs of Lin-28, Lin28 (also called Lin28A) and Lin28B, are promising cancer biomarkers. This meta-analysis was performed to evaluate the prognostic values of Lin28A and Lin28B in multiple human malignancies. Methods Systematic searches of the PubMed, Web of Science and Embase were used to identify relevant studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), or progression-free survival (PFS) were respectively calculated. Results 3772 Lin28A-associated patients and 1730 Lin28B-related cases were ultimately enrolled in this meta-analysis. The elevated expression level of Lin28A was significantly associated with poor OS (HR = 1.60, P

The major purpose of the present study was to investigate the efficacy and feasibility of the Mullerian duct cyst treatment by transurethral electrotomy combined with seminal vesiculoscopy. The clinical data of 20 aspermia patients who presented with Mullerian Cyst between March 2009 and March 2016 were retrospectively analyzed in the present study. Semen specimens of all patients were obtained by masturbation or sperm collector and diagnosed as aspermia by semen analysis (including sperm count, semen volume, sperm density, pH and fructose level). By transrectal ultrasonography, magnetic resonance imaging and testicular biopsy, the diagnosis of Mullerian cyst inducing obstruction aspermia was correctly identified. All patients were treated with the combination of transurethral resection and seminal vesiculoscopy. The operation time was 30–50 min. The follow-up duration after the operation was 12 months. All subjects included in the present study successfully underwent the operation. The semen quality of all patients was greatly improved and sperms were detected in semen specimens. The semen routine examination results of 3 consecutive follow-up exams within 12 months were within the normal range. The ejaculate volume and semen fructose levels were significantly higher than those prior to surgery (P

Additional file 1: Table S1. Main characteristics of studies on Lin28 (Lin28A) and cancer prognosis.

The purpose of this study was to describe the first metabolic profile of human sperm cells through the application of an untargeted platform based on gas chromatography-mass spectrometry (GC-MS). Sperm cell samples from patients diagnosed with idiopathic asthenozoospermia (n=30) and healthy subjects (n=30) were analyzed using a nontargeted metabolomics method based on GC-MS spectroscopy. The mass spectrometric data were collected using multivariate and univariate analyses to identify metabolites related to idiopathic asthenozoospermia. By using metabolomic strategies, we identified 33 metabolites, 27 of which were decreased in the idiopathic asthenozoospermia group compared with the normozoospermic group and six were increased in idiopathic asthenozoospermia. With respect to human sperm cells, some of these metabolites are reported here for the first time. Pathways for nucleoside, amino acid and energy metabolism, and the Krebs cycle were disturbed and were associated with idiopathic asthenozoospermia. The metabolic profiling provides an important first step in studying the pathophysiological mechanisms involved in IAS, and the identified metabolites may become potential biomarkers for its diagnosis and treatment.