Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification.

Glycolysis-related metabolic reprogramming is a central hallmark of human cancers, especially in renal cell carcinoma. However, the regulatory function of glycolytic signature in papillary RCC has not been well elucidated. In the present study, the glycolysis-immune predictive signature was constructed and validated using WGCNA, glycolysis-immune clustering analysis. PPI network of DEGs was constructed and visualized. Functional enrichments and patients' overall survival were analyzed. QRT-PCR experiments were performed to detect hub genes' expression and distribution, siRNA technology was used to silence targeted genes; cell proliferation and migration assays were applied to evaluate the biological function. Glucose concentration, lactate secretion, and ATP production were measured. Glycolysis-Immune Related Prognostic Index (GIRPI) was constructed and combined analyzed with single-cell RNA-seq. High-GIRPI signature predicted significantly poorer outcomes and relevant clinical features of pRCC patients. Moreover, GIRPI also participated in several pathways, which affected tumor immune microenvironment and provided potential therapeutic strategy. As a key glycolysis regulator, PFKFB3 could promote renal cancer cell proliferation and migration in vitro. Blocking of PFKFB3 by selective inhibitor PFK-015 or glycolytic inhibitor 2-DG significantly restrained renal cancer cells' neoplastic potential. PFK-015 and sunitinib could synergistically inhibit pRCC cells proliferation. Glycolysis-Immune Risk Signature is closely associated with pRCC prognosis, progression, immune infiltration, and therapeutic response. PFKFB3 may serve as a pivotal glycolysis regulator and mediates Sunitinib resistance in pRCC patients.

Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma.

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevalent cancers worldwide. Accumulating evidence revealed that copper-induced cell death played a vital role in various tumors. However, the underlying mechanism of cuproptosis with molecular heterogeneity and tumor microenvironment (TME) in ccRCC remains to be elucidated. The present study aimed to discover the biological function of cuproptosis regulators with the potential to guide clinical therapy. Methods: Using Single-cell RNA-seq, bulk transcriptome and other multi-omics datasets, we identify essential cuproptosis-related hub gene PDHB for further study. The dysregulation of PDHB in ccRCC was characterized, together with survival outcomes, pathway enrichment and immune infiltration among tumor microenvironments. The functional significance and clinical association of PDHB was validated with loss of function experiments and surgical removal specimens. Results: PDHB mRNA and protein expression level was significantly downregulated in ccRCC tissues compared with normal and paired normal tissues. Clinicopathological parameters and tissue microarray (TMA) indicated that PDHB was identified as a prognostic factor for survival outcomes among ccRCC patients. Additionally, low PDHB was negatively correlated with Treg cells, indicating an immunosuppressive microenvironment. Mechanistically, knockdown PDHB appeared to promote the RCC cells proliferation, migration, and invasion potentials. Subsequent studies showed that copper-induced cell death activation could overcome sunitinib resistance in RCC cells. Conclusion: This research illustrated a cuproptosis-related hub gene PDHB which could serve as a potential prognostic marker and provide therapeutic benefits for clinical treatment of ccRCC patients.

In silico, in vitro and in vivo studies: Dibutyl phthalate promotes prostate cancer cell proliferation by activating Forkhead Box M1 and remission after Natura-α pretreatment.

Dibutyl phthalate (DBP) is widely used in perfumes, cosmetics, shampoos and medical devices. It is ubiquitous in the environment and greatly endangers people's health. Several studies have reported that being exposed to it can promote the development of lung cancer, breast cancer, hepatoma, and multiple myeloma. However, there are still few studies on the specific molecular mechanism and prevention methods of DBP promoting the progression of prostate cancer. This study, in silico, in vitro and in vivo, aims to explore the promoting effect of DBP on prostate cancer cell proliferation. In silico analysis, we obtained a set of DBP interactive genes by utilizing TCGA, CTD and GEO database. These genes are mainly enriched in cell cycle regulatory pathways and they have high degree of homogeneity. We found that these genes shared one transcription factor - Forkhead Box M1 (FOXM1) by performing Chip-X Enrichment Analysis (Version 3.0). FOXM1, once called the 2010 Molecule of the Year, aberrantly expressed in up to 20 kinds of tumors. In vitro experiments, we used DBP at concentrations of 10-8 M and 5 * 10-7 M to treat C4-2 and PC3 cells for 6 days, respectively. Cell viability was promoted significantly. When Natura-α was added in the background of above-mentioned concentration of DBP, this effect was significantly inhibited. In addition, we also found that DBP can interfering with the efficacy of enzalutamide therapy. The introduction of Natura-α can also reverse this phenomenon. In vivo, subcutaneous tumor formation experiments in nude mice, 800 mg/kg/day DBP can promote the growth of prostate cancer. This phenomenon was suppressed when Natura-α (100 mg/kg/day) was added. Based on the results of the above three levels, we confirmed that DBP can target FOXM1 to promote prostate cancer cell proliferation. Natura-α can reverse its cancer-promoting effect. This study provides new insights into the impact of DBP on prostate cancer.

CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer.

Prostate cancer harboring BRCA1/2 mutations are often exceptionally sensitive to PARP inhibitors. However, genomic alterations in other DNA damage response genes have not been consistently predictive of clinical response to PARP inhibition. Here, we perform genome-wide CRISPR-Cas9 knockout screens in BRCA1/2-proficient prostate cancer cells and identify previously unknown genes whose loss has a profound impact on PARP inhibitor response. Specifically, MMS22L deletion, frequently observed (up to 14%) in prostate cancer, renders cells hypersensitive to PARP inhibitors by disrupting RAD51 loading required for homologous recombination repair, although this response is TP53-dependent. Unexpectedly, loss of CHEK2 confers resistance rather than sensitivity to PARP inhibition through increased expression of BRCA2, a target of CHEK2-TP53-E2F7-mediated transcriptional repression. Combined PARP and ATR inhibition overcomes PARP inhibitor resistance caused by CHEK2 loss. Our findings may inform the use of PARP inhibitors beyond BRCA1/2-deficient tumors and support reevaluation of current biomarkers for PARP inhibition in prostate cancer.

SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner.

BACKGROUND: Renal clear cell carcinoma (ccRCC) is the most prevalent tumors worldwide. Discovering effective biomarkers is essential to monitor the prognosis and provide alternative clinical options. SPTBN1 is implicated in various cancerous processes. However, its role in ccRCC remains unelucidated. This study intends to explore the biological function and mechanism of SPTBN1 in ccRCC. METHODS: Single-cell and bulk RNA-seq, tissue microarray, real-time quantitative PCR, and western blotting were applied to verify the expression and predictive value of SPTBN1 in ccRCC. Gain or loss of functional ccRCC cell line models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Actinomycin D experiment, RNA immunoprecipitation (RIP), specific inhibitors, and rescue experiments were carried out to define the molecular mechanisms. RESULTS: SPTBN1 was down-regulated in ccRCC and knockdown of SPTBN1 displayed a remarkably oncogenic role both in vitro and in vivo; while overexpressing SPTBN1 reversed this effect. SPTBN1 mediated ccRCC progression via the pathway of glutamate pyruvate transaminase 2 (GPT2)-dependent glycolysis. The expression of GPT2 was significantly negatively correlated with that of SPTBN1. As an RNA binding protein SPTBN1, regulated the mRNA stability of GPT2. CONCLUSION: Our research demonstrated that SPTBN1 is significantly down-regulated in ccRCC. SPTBN1 knockdown promotes ccRCC progression via activating GPT2-dependent glycolysis. SPTBN1 may serve as a therapeutic target for the treatment of ccRCC.

Essential m6A Methylation Regulator HNRNPC Serves as a Targetable Biomarker for Papillary Renal Cell Carcinoma.

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.

RB1 loss overrides PARP inhibitor sensitivity driven by RNASEH2B loss in prostate cancer.

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.

Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1.

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.

Identification of autophagy-related long non-coding RNA prognostic and immune signature for clear cell renal cell carcinoma.

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.

TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner.

BACKGROUND: Ubiquitylation 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. METHODS: RCC 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. RESULTS: We 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-ß1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our 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-ß1 signaling in regulating cancerous malignancies.

High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity.

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 < 0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P < 0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P < 0.001) and tumor mutational burden (TMB, P < 0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways. CONCLUSIONS: CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.

Acinar with ductal and mucinous adenocarcinoma of prostate cancer complicated with lung metastasis: a case report and literature review.

Acinar adenocarcinoma, ductal adenocarcinoma and mucinous adenocarcinoma are the subtypes of prostate cancer (PCa). Most of the pathological types of PCa are acinar adenocarcinoma, while ductal adenocarcinoma and mucinous adenocarcinoma are uncommon. The case of acinar adenocarcinoma with ductal and mucinous adenocarcinoma has not been reported before. Herein, we report a treatment experience involving a 72-year-old man who presented similarly as most PCa patients, but the pathologic diagnosis was acinar adenocarcinoma with focal ductal and mucinous adenocarcinoma differentiating. Besides, this case is associated with lung metastasis, after radical prostatectomy (RP) and endocrine therapy the pulmonary nodule exerted a shrinking trend and the PSA level of this patient is still maintained at 0 ng/ mL till now. Through literature review, we found that patients who diagnosed as mixed pathological type of PCa had a lower survivor than pure PCa patients. Furthermore, there is no corresponding consensus or guideline for treating such multiple differentiated PCa patients. Surprisingly, this patient showed a high sensitivity to androgen deprivation therapy (ADT). Although the tumor presented aggressiveness, the followup results were satisfactory and we will continue to pay attention to his physical condition. We report this case to provide a treatment strategy for the patients with multi-differentiated PCa complicated with organ metastases.

Effect of Enhanced Recovery After Surgery on Postoperative Recovery and Quality of Life in Patients Undergoing Laparoscopic Partial Nephrectomy.

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.

Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma.

Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

MicroRNA-195 inhibits proliferation and metastasis in renal cell carcinoma via regulating HMGA1.

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.

Comprehensive managements of metastatic renal tumor with Mayo III inferior vena cava tumor thrombus: a case report.

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.

lncRNA MIR4435-2HG promoted clear cell renal cell carcinoma malignant progression via miR-513a-5p/KLF6 axis.

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.

The management and composition of symptomatic seminal vesicle calculi: aetiological analysis and current research.

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.

Prognostic value of Lin28A and Lin28B in various human malignancies: a systematic review and meta-analysis.

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 < 0.001) and poor RFS/DFS/PFS (HR = 1.62, P < 0.001) in patients with malignancies. Lin28B overexpression significantly correlated with unfavorable OS (HR = 1.72, P < 0.001) and RFS/DFS/PFS (HR = 2.35, P < 0.001) of human malignancies. CONCLUSIONS: Lin28A and Lin28B possess significant prognostic values in various human malignancies. Overexpression of Lin28A or Lin28B suggests poor prognosis for cancer patients.

Treatment of Mullerian duct cyst by combination of transurethral resection and seminal vesiculoscopy: An initial experience.

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<0.05). Furthermore, at 12 months post-operatively, the seminal vesicles of 6 patients were smaller than at the pre-operative stage. In conclusion, transurethral resection combined with seminal vesiculoscopy may be an effective and feasible option for the treatment of patients with Mullerian duct cyst.