Development and validation of two nomograms for predicting overall survival and Cancer-specific survival in prostate cancer patients with bone metastases: a population-based study.

BACKGROUND: Prostate cancer with bone metastasis has significant invasiveness and markedly poorer prognosis. The purpose of this study is to establish two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of prostate cancer patients with bone metastasis. METHODS: From January 2000 to December 2018, a total of 2683 prostate adenocarcinoma with bone metastasis patients were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. These patients were then divided into a training cohort and a validation cohort, with OS and CSS as the study endpoints. Correlation analyses were employed to assess the relationship between variables. Univariate and multivariate Cox analyses were utilized to ascertain the independent prognostic factors. Calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were employed to evaluate discrimination and calibration of the nomogram. DCA was applied to examine accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Lastly, the risk stratifications of the nomogram and the AJCC Stage System were compared. RESULTS: There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that seven variables (age, surgery, brain metastasis, liver metastasis, lung metastasis, Gleason score, marital status) and six variables (age, surgery, lung metastasis, liver metastasis, Gleason score, marital status) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. CONCLUSION: Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of PABM patients.

Integrative analysis of triphenyl phosphate: contextual interpretation of bladder cancer cohort.

In recent years, organophosphate ester flame retardants (OPFRs) have emerged as preferred alternatives to brominated flame retardants (BFRs) in materials such as building supplies, textiles, and furnishings. Simultaneously, a notable surge in bladder cancer incidences has been observed globally, particularly in developed nations, placing it as the 10th most prevalent cancer type. Among the extensive OPFRs, the linkage between triphenyl phosphate (TPP) and bladder cancer remains inadequately investigated. Hence, our study endeavors to elucidate this potential association. We sourced transcriptome profiles and TPP-related data from The Cancer Genome Atlas and Comparative Toxicogenomics databases. Using the ssGSEA algorithm, we established TPP-correlated scores within the bladder cancer cohort. Differentially expressed analysis enabled us to identify key genes in bladder cancer patients. We utilized the LASSO regression analysis, along with univariate and multivariate COX regression analyses to construct a prognostic prediction model. To uncover critical pathways involving key genes, we employed GSEA and GSVA enrichment analyses. Molecular docking analysis was performed to determine the binding capability between TPP and proteins. Our findings reveal that the TPP-centric risk model offers valuable prediction for bladder cancer cohorts. Furthermore, the reliability of this TPP-influenced risk model was verified through ROC curve analysis and survival studies. Intriguingly, TPP exposure appears to bolster the proliferation and invasiveness of bladder cancer cells. This study furnishes new insights into the possible benefits of minimizing TPP exposure for hindering bladder cancer progression.

Causes of death after testicular cancer diagnosis: a US population-based analysis.

BACKGROUND: After the introduction of cisplatin-based chemotherapy, the survival time of testicular cancer (TC) patients has improved dramatically. However, the overall risk of death in patients with TC remains significantly higher than in the general population. The aim of this study was to assess and quantify the causes of death after TC diagnosis. METHOD: In total, 44,975 men with TC in the United States diagnosed and registered by the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2018 were studied. In this study, standardized mortality rates (SMRs) were calculated for each cause of death in TC individuals and further analyzed in strata according to age and race. RESULT: Of the included participants, 3,573 (7.94%) died during the follow-up period. The greatest proportion of deaths (38.20%) occurred within 1 to 5 years after diagnosis. Most deaths occurred from TC itself and other cancers. For non-malignant conditions, the most common causes of death within 1 years after diagnosis were accidents and adverse effects (53, 4.75%) followed by diseases of heart (45, 4.04%). However, > 1 years after diagnosis, the most common noncancer causes of death were heart diseases. Results of stratified analysis show that non-Hispanic White TC participants have a lower SMR (0.68, 95% CI, 33.39-38.67) from Cerebrovascular Diseases than the general U.S. CONCLUSIONS: Although TC remains the most common cause of death after TC diagnosis, other non-TC causes of death represent a significant number of deaths among TC men. These findings help TC survivors understand the various health risks that may occur at different follow-up periods.

Incremental value of radiomics with machine learning to the existing prognostic models for predicting outcome in renal cell carcinoma.

Purpose: To systematically evaluate the potential of radiomics coupled with machine-learning algorithms to improve the predictive power for overall survival (OS) of renal cell carcinoma (RCC). Methods: A total of 689 RCC patients (281 in the training cohort, 225 in the validation cohort 1 and 183 in the validation cohort 2) who underwent preoperative contrast-enhanced CT and surgical treatment were recruited from three independent databases and one institution. 851 radiomics features were screened using machine-learning algorithm, including Random Forest and Lasso-COX Regression, to establish radiomics signature. The clinical and radiomics nomogram were built by multivariate COX regression. The models were further assessed by Time-dependent receiver operator characteristic, concordance index, calibration curve, clinical impact curve and decision curve analysis. Result: The radiomics signature comprised 11 prognosis-related features and was significantly correlated with OS in the training and two validation cohorts (Hazard Ratios: 2.718 (2.246,3.291)). Based on radiomics signature, WHOISUP, SSIGN, TNM Stage and clinical score, the radiomics nomogram has been developed. Compared with the existing prognostic models, the AUCs of 5 years OS prediction of the radiomics nomogram were superior to the TNM, WHOISUP and SSIGN model in the training cohort (0.841 vs 0.734, 0.707, 0.644) and validation cohort2 (0.917 vs 0.707, 0.773, 0.771). Stratification analysis suggested that the sensitivity of some drugs and pathways in cancer were observed different for RCC patients with high-and low-radiomics scores. Conclusion: This study showed the application of contrast-enhanced CT-based radiomics in RCC patients, creating novel radiomics nomogram that could be used to predict OS. Radiomics provided incremental prognostic value to the existing models and significantly improved the predictive power. The radiomics nomogram might be helpful for clinicians to evaluate the benefit of surgery or adjuvant therapy and make individualized therapeutic regimens for patients with renal cell carcinoma.

Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents.

In the recent decades, obesity rates among children and adolescents, especially males, have increased significantly. This worldwide phenomenon is thought to significantly affect the levels of sex hormones. However, the association between waist circumference (a marker of abdominal obesity) and sex hormone levels in children and adolescents is unknown. In this study, 4031 participants aged 6-19 years from the United States National Health and Nutrition Examination Survey (NHANES) in the USA were enrolled in this study. The common confounders of age, race, body mass index, educational level, family income, diabetes, and time of sample collection were also collected. The participants missing any of the above information were excluded from the study. We used multiple linear regression and other multiple statistics to assess the associations between waist circumference and serum testosterone, estradiol, sex hormone-binding globulin (SHBG), free androgen index (FAI), and testosterone/estradiol ratio (T/E2). Waist circumference remained associated with sex hormone levels in children and adolescents after controlling for covariates. As waist circumference increases, testosterone levels in children and adolescents show an overall decline after a brief increase, with the inflection point for waist circumference of 65-66 cm. In addition, waist circumference positively correlates with estradiol levels in male children (ß = 0.007, 95% confidence interval: 0.004-0.009). Moreover, circulating SHBG decreases in children and adolescents as waist circumference increases. In conclusion, this study highlighted waist circumference as a vital indicator affecting sex hormone levels in children and adolescents.

[Corrigendum] MicroRNA­379­5p plays a tumor­suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2.

Following the publication of the above article, an interested reader drew to the authors' attention that the cell and invasion migration assay data featured in Figs. 2C and 5D contained two pairs of overlapping panels, such that the data appeared to have been derived from the same original sources, even though the data panels were intending to show the results from differently performed experiments. Moreover, there was also an instance of duplicated data panels comparing between the si­NC/cell invasion and si­NC/cell migration assay panels in Fig. 4C. After having examined their original data, the authors have realized that inadvertent errors were made during the process of compiling these figures. Corrected versions of Figs. 2, 4 and 5, incorporating all the data from one of the repeated experiments, are shown opposite and on the next page. The authors all agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also regret any inconvenience caused to the readership of the Journal. [Oncology Reports 57: 3502­3508, 2017; DOI: 10.3892/or.2017.5607].

Integrative analysis of TRPV family to prognosis and immune infiltration in renal clear cell carcinoma.

The transient receptor potential vanilloid (TRPV) family has been preliminarily discovered to play an important role in various cancers, including clear cell renal cell carcinoma (ccRCC), which is closely associated with immune infiltration. However, the expression and prognosis of TRPV family and tumor-infiltrating immune cells in ccRCC are obscure. This study aimed to explore the prognostic and therapeutic value of the TRPV family expression in ccRCC from the perspective of bioinformatics. We analyzed the transcriptome and clinical data of kidney renal clear cell carcinoma (KIRC) from The Cancer Genome Atlas (TCGA) database. A clustering analysis and immune infiltration analysis were conducted to investigate the influence of the TRPV family genes on ccRCC. Our study found that the TRPV family is an excellent prognostic stratification for ccRCC. Among them, TRPV3 is the most significant prognostic marker of ccRCC. In addition, we performed a drug sensitivity analysis to identify the drugs with the strongest association with TRPV3. As a result, the TRPV family, particularly TRPV3, can act as a prognostic biomarker in ccRCC to determine prognosis and levels of immune infiltration.

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.

Integrated Analysis of the Prognosis-Associated RNA-Binding Protein Genes and Candidate Drugs in Renal Papillary Cell Carcinoma.

RNA-binding proteins (RBPs) play significant roles in various cancer types. However, the functions of RBPs have not been clarified in renal papillary cell carcinoma (pRCC). In this study, we identified 31 downregulated and 89 upregulated differentially expressed RBPs on the basis of the cancer genome atlas (TCGA) database and performed functional enrichment analyses. Subsequently, through univariate Cox, random survival forest, and multivariate Cox regression analysis, six RBPs of SNRPN, RRS1, INTS8, RBPMS2, IGF2BP3, and PIH1D2 were screened out, and the prognostic model was then established. Further analyses revealed that the high-risk group had poor overall survival. The area under the curve values were 0.87 and 0.75 at 3 years and 0.78 and 0.69 at 5 years in the training set and test set, respectively. We then plotted a nomogram on the basis of the six RBPs and tumor stage with the substantiation in the TCGA cohort. Moreover, we selected two intersectant RBPs and evaluate their biological effects by GSEA and predicted three drugs, including STOCK1N-28457, pyrimethamine, and trapidil by using the Connectivity Map. Our research provided a novel insight into pRCC and improved the determination of prognosis and individualized therapeutic strategies.

Male reproductive toxicity of perfluorooctanoate (PFOA): Rodent studies.

Perfluorooctanoic acid (PFOA) is an artificial organic substance widely used for decades, which seriously threatens human health. This study aimed to identify human-relevant correlates between PFOA exposure and the male rodent reproductive system. We performed a systematic literature review of the relevant literature of PubMed, Cochrane Library databases, Web of Science and Embase from the establishment to April 2020. Studies included the effects of PFOA on the reproductive system of male rodents. The meta-analysis was performed on the basis of the following points: level of testosterone and estradiol in serum, development of reproductive organs, pathological changes of reproduction organs and parameters of semen. A series of 16 studies was enrolled in this study. The standard mean difference (SMD) for PFOA-related reproductive toxicity was summarised as -0.39 (95% confidence interval [CI]: 0.71, -0.07). The lower serum testosterone levels, decreased absolute testicular and epididymal weights, higher serum estradiol levels, elevated relative testicular and seminal vesicle weights and increased incidence of Leydig cell adenoma and percentage of abnormal sperm were observed in the exposed group compared with the control group. However, no statistical difference was found in the day of preputial separation of pups and percentage of motile sperm. In conclusion, PFOA exposure heightens the reproductive system damage in male rodents. However, many studies included in the review did not identify mechanisms by which PFOA induces changes to the male reproductive system, which is an area for additional study.

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.

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.

Toxicity of polybrominated diphenyl ethers (PBDEs) on rodent male reproductive system: A systematic review and meta-analysis of randomized control studies.

Polybrominated diphenyl ethers (PBDEs) are a group of environmental endocrine-disrupting chemicals (EDCs). According to recent studies, the associations between PBDEs and rodent male reproductive system are controversial. Therefore, we performed this systematic review and meta-analysis to clarify the effects of PBDEs on rodent male reproductive system. Data were extracted from articles collected from PubMed, Web of Science, and other databases. The pooled standard mean deviation (SMD) with 95% confidence interval (95% CI) was used to evaluate the association between the male rodent reproductive system impairment and PBDE exposure. Ten articles were included in the present meta-analysis and systematic review. The summary SMD of reproductive toxicity associated with PBDEs was -0.46 (95% CI: -0.69, -0.22), and the overall association between DE-71 along with BDE-209 and male reproductive system damage was statistically significant (SMD = -0.7 95% CI: -1.18, -0.21, p = .041; SMD = -0.41, 95% CI: -0.77, -0.05, p = .000). The adverse impact of PBDEs on rodent male reproductive system, especially seminal vesicle (SMD = -1.09, 95% CI: -1.49, -0.49, p = .523) and ventral prostate (SMD = -1.27, 95% CI: -1.88, -0.65, p = .821), were clearly demonstrated. Moderate (SMD = -0.81, 95% CI: -1.182, -0.437, p = .197) and high (SMD = -0.41, 95% CI: -0.76, -0.05, p = .000) dosage may have exerted effect than relatively low (SMD = -0.29, 95% CI: -0.17, 0.12, p = .136) dosage. In conclusion, our meta-analysis and systematic review suggested PBDE toxicity on the male reproductive system.

SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies in the world, and tumor metastasis is still the main reason for disease progression. Accumulating evidence shows that SH3BGRL2 may play a key role in tumor progression and metastasis. However, the role of SH3BGRL2 in ccRCC has not been systematically investigated and remains elusive. METHODS: The clinical significance of SH3BGRL2 was evaluated by bioinformatic analysis and tissue microarray (TMA) samples. SH3BGRL2 expression was determined by RT-PCR, western blot and immunohistochemistry staining. Tumor suppressive effect of SH3BGRL2 was determined by both in vitro and in vivo studies. Western blot, chromatin immunoprecipitation assay and luciferase report assay were applied for mechanism dissection. FINDINGS: SH3BGRL2 was crucial for epithelial-mesenchymal transition (EMT) progression and metastasis in ccRCC. Clinically, SH3BGRL2 was identified as an independent prognostic factor for ccRCC patients. Gain- and loss-of-function results suggested that SH3BGRL2 played a critical role in cell proliferation, migration and invasion. Mechanistically, we found that SH3BGRL2 acted as a tumor suppressor through Hippo/TEAD1 signaling, then TEAD1 altered Twist1 expression at the transcriptional level via directly binding to its promoter region. INTERPRETATION: Our findings established that SH3BGRL2 performed as a tumor suppressor and modulator via Hippo/TEAD1-Twist1 signaling in ccRCC, and the alteration of SH3BGRL2 could serve as a functional response biomarker of tumor progression and metastasis in 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.

Robot-assisted radical cystectomy with totally intracorporeal neobladder diversion: perioperative, oncologic, and functional outcomes.

BACKGROUND: The use of robot-assisted radical cystectomy (RARC) has increased rapidly in the past decade. However, reports of intracorporeal neobladder diversion remain limited. This article aimed to provide the surgical steps for RARC with totally intracorporeal neobladder diversion and the present perioperative, oncologic, and functional outcomes. METHODS: Between June 2017 and January 2020, RARC with intracorporeal neobladder diversion was performed in 12 male patients. Perioperative variables, pathologic data, early and late complications, urinary continence, potency, and recurrence-free survival were evaluated as outcome measures. RESULTS: The surgery was successful in all cases without open conversion. The median operative time, estimated blood loss, and postoperative hospital stay were 419 min (range, 315-640 min), 400 mL (range, 250-1,200 mL), and 14.5 days (range, 9-25 days), respectively. No positive surgical margins nor lymph nodes were observed. Eleven minor (grades 1 and 2) and one major (grades 3-5) complications were found in the early (0-30 days) period and six minor and one major complications in the late (>30 days) period. The median follow-up time was 13.1 months (range, 5.4-32.0 months), and two patients died due to metastatic disease. At 6 months after surgery, the daytime continence rate was 90.0%, while the nighttime continence rate was 80.0%. Only two patients (16.7%) reported capability of potency. The study was limited by a small sample size and short follow-up. CONCLUSIONS: RARC with intracorporeal neobladder is a complex procedure but technically feasible with acceptable oncologic and functional outcomes. Studies with long-term follow ups and increased number of cases and randomized trials are indispensable to assess the potential of this technique.

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.

Genetic variations in MAGE-A11 predict the risk and survival of renal cell cancer.

Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract, which plays an important role in tumorigenesis. Single-nucleotide polymorphisms (SNPs) have been shown to contribute to cancer risk and prognosis. However, the role of SNPs of MAGE-A11 in renal cell carcinoma (RCC) has not been established. Two intronic SNPs (rs6641352 and rs6540341) of MAGE-A11 have been screened to assess their associations with RCC risk and prognosis in a case control study. We found that rs6641352 was associated with RCC susceptibility in the dominant model (TC/CC vs. TT, adjusted odds ratio = 1.315, 95% confidence interval [CI] = 1.089-1.588) and with survival of RCC in the recessive model (CC vs. TT/TC, adjusted hazard ratio = 3.526, 95% CI = 1.072-11.595). For the SNP rs6540341, individuals with the T allele could have a critically increased risk of RCC (adjusted odds ratio = 1.301, 95% CI = 1.081-1.564, P = 0.005 in the dominant model). However, there was no significant association between rs6540341 and RCC survival. Hence, rs6641352 in MAGE-A11 may contribute to the genetic susceptibility and prognosis for RCC and act as a biomarker for RCC occurrence and prognosis.

MicroRNA-188 inhibits proliferation migration and invasion of prostate carcinoma by targeting at MARCKS.

Recent evidences suggested that miRNAs process key roles in the biological behaviors and the development of prostate carcinoma (PC). However, its molecular mechanism in PC is still remained largely unclear. In this study, the expression level of miR-188 and the protein expression of MARCKS were detected by RT-PCR and western blot, respectively. Moreover, we determined the oncogene or anti-oncogene role of miR-188 in the PC through gain and loss function assay of miR-188 using transfection of miR-188 mimics and inhibitor. Meanwhile, luciferase reporter vectors with miR-188 mimics were constructed and transfected into PC cells. Our data indicated that the expression of miR-188 was dramatically reduced in human PC tissues and cell lines and the increased miR-188 levels obviously inhibited the proliferation, migration and invasion of PC cells and negatively regulative with MARCKS. Together, our findings proved that miR-188 plays an inhibitive role in PC of proliferation, migration and invasion at least in part via suppressing MARCKS expression, which could be regarded as a promising therapeutic target in PC.

Genetic variants in a long noncoding RNA related to Sunitinib Resistance predict risk and survival of patients with renal cell carcinoma.

OBJECTIVE: LncARSR (lncRNA Activated in RCC with Sunitinib Resistance, ENST00000424980) is a newly identified lncRNA to promote the sunitinib resistance of renal cell carcinoma (RCC), which may contribute to tumorigenesis and progression. This study aimed to explore the association of lncARSR tagSNPs with the risk and prognosis of RCC. METHODS: In this study, a 2-stage case-control study was performed to evaluate the association between 2 tagging SNPs (rs1417080 and rs7859384) and RCC susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by unconditional logistic regression analyses. Different survival time was estimated by the Kaplan-Meier method and compared by the Log-rank test. Hazard ratios (HRs) and their 95% CIs were calculated to determine predictive factors by Cox proportion hazards model. RESULTS: When combing discovery and validation sets together, rs7859384 was determined to be significantly associated with the decreased RCC risk with all P < 0.05 in 4 models (co-dominant model, additive model, dominant model and recessive model). stratified analyses showed prominent risk effect of SNP rs7859384 GA/GG genotypes was found in clinical subgroups of stage I and stage II (P = 0.009, OR = 0.77, 95% CI = 0.64-0.94) and individuals with clear cell RCC (P = 0.014, OR = 0.79, 95% CI = 0.65-0.95). A protective effect of SNP rs7859384 GA/GG genotypes was observed among individuals with BMI > 24 (P = 0.025, OR = 0.74, 95% CI = 0.56-0.96), without hypertension (P = 0.037, OR = 0.79, 95% CI = 0.63-0.99), without family history of cancer (P = 0.048, OR = 0.83, 95% CI = 0.68-1.00). Survival analyses revealed individuals with GA/GG genotypes had higher survival rate compared with the corresponding AA wild genotypes in the dominant model (log-rank P = 0.005, adjusted HR = 0.34, 95% CI = 0.16-0.73). CONCLUSION: This study suggests that rs7859384 of lncARSR was associated with RCC susceptibility and may act as a prognostic biomarker for patients with RCC.