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LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients’ tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.

Hemangioma of the prostate is rarely reported. We here describe a hemangioma of the prostate in a 31-year-old man.The history, imaging characteristics, treatment and one year follow-up results were well documented. The chief complaint was retrograde ejaculation. A 3.1 cm × 2.9 cm mass in the prostate was detected by ultrasound. Transurethral resection of the prostate (TURP) was performed.Pathological examination revealed the mass was hemangioma. Immunohistochemical study found the tissue was SMA, CD34, CD31 positive, but D2-40 negative. Imaging feature combined with pathological result suggests the diagnosis of hemangioma of the prostate. One year follow-up revealed the patient was infertile.We suggest TURP should be performed to remove the hemangioma. Combined treatment is necessary to resolve the patient's infertility.

Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. We downloaded somatic mutation data for 46,697 patients and tumor-infiltrating immune cells levels data for 11070 patients, then combined TP53 and BRAF mutation status into a biomarker model and found that the predict ability of TP53/BRAF mutation model is more powerful than some past models. Commonly, patients with high-TMB status have better response to ICI therapy than patients with low-TMB status. However, the genotype of TP53

Summary Background Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. Methods In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. Findings Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660–0·826] in region 1, 0·734 [0·651–0·814] in region 2, and 0·736 [0·649–0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81–10·07] in the internal testing set, 5·39 [3·38–8·59] in the independent validation set, and 4·62 [2·48–8·61] in the TCGA set; all p Interpretation Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. Funding National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

Background: To investigate the value of contrast-enhanced transrectal ultrasound (CETRUS) in reducing unnecessary biopsy during prostate cancer screening and predicting biochemical recurrence in patients with localized prostate cancer. Methods:This was a prospective study of patients suspected of prostate cancer who were evaluated with CETRUS followed by prostate biopsy. Prostate blood flow on CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcomes was analyzed; Univariate and multi-variate analyses were used to determine the probable prognostic factors with biochemical recurrence in patients with localized prostate cancer underwent radical prostatectomy. Results:A total of 347 patients were enrolled. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer. Using CETRUS score ≥ 2 as the threshold for biopsy could have reduced the number of biopsies by 12.1% (42/347) without missing cancer and spared 23.0% (42/183) of patients from unnecessary biopsy. 77 patients with localized prostate cancer underwent radical prostatectomy and followed up. 17 of 77 patients exhibited biochemical recurrence. The 3-year biochemical recurrence-free survival rates were 86% for patients with CETRUS low scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis showed that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00-24.69; p = 0.002). Conclusions:CETRUS score may be a useful tool to reduce unnecessary biopsy during prostate cancer screening and predict biochemical recurrence of localized prostate cancer after radical prostatectomy.

We previously demonstrated that amplified in breast cancer 1 (AIB1) and eukaryotic initiation factor 2 (EIF5A2) overexpression was an independent predictor of poor clinical outcomes for patients with bladder cancer (BCa). In this study, we evaluated the usefulness of AIB1 and EIF5A2 alone and in combination with nuclear matrix protein 22 (NMP22) as noninvasive diagnostic tests for BCa. Using urine samples from 135 patients (training set, controls [n = 50] and BCa [n = 85]), we detected the AIB1, EIF5A2, and NMP22 concentrations using enzyme-linked immunosorbent assay. We applied multivariate logistic regression analysis to build a model based on the three biomarkers for BCa diagnosis. The diagnostic accuracy of the three biomarkers and the model were assessed and compared by the area under the curve (AUC) of the receiver operating characteristic. We validated the diagnostic accuracy of these biomarkers and the model in an independent validation cohort of 210 patients. In the training set, urinary concentrations of AIB1, EIF5A2, and NMP22 were significantly elevated in BCa. The AUCs of AIB1, EIF5A2, NMP22, and the model were 0.846, 0.761, 0.794, and 0.919, respectively. The model had the highest diagnostic accuracy when compared with AIB1, EIF5A2, or NMP22 (p < 0.05 for all). The model had 92% sensitivity and 92% specificity. We obtained similar results in the independent validation cohort. AIB1 and EIF5A2 show promise for the noninvasive detection of BCa. The model based on AIB1, EIF5A2, and NMP22 outperformed each of the three individual biomarkers for detecting BCa.

Eukaryotic translation initiation factor (EIF) 5A2 exerts important functions that regulate the development and progression of cancers. The present study aimed to investigate the expression of EIF5A2 in prostate cancer (PCa) and its association with biological and prognostic significance. EIF5A2 mRNA and protein levels were analyzed in three paired samples of freshly resected PCa and adjacent non-tumor tissues. Immunohistochemical staining was used to detect the expression of EIF5A2 protein levels in 72 paraffin-embedded PCa tumor specimens. Subsequently, the association between EIF5A2 protein expression and clinicopathological parameters was assessed. Semi-quantitative reverse transcription-polymerase chain reaction and western blot analyses showed both EIF5A2 mRNA and protein levels were elevated in PCa compared with adjacent non-tumor tissues. Elevated EIF5A2 protein levels were observed in 73.6% (53/72) of the clinical PCa tissues using immunohistochemical staining. EIF5A2 expression was significantly associated with tumor stage (P=0.011) and biochemical recurrence status (P=0.032). Additionally, high levels of EIF5A2 predicted worse progression-free survival (P=0.007). Multivariate Cox regression analysis indicated that high expression of EIF5A2 was an independent prognostic factor for poor progression-free survival (hazard ratios, 0.366; 95% confidence interval, 0.349–0.460; P=0.021). The present study demonstrated that EIF5A2 is overexpressed in prostate cancer and may be a potential predictor and therapeutic target in PCa patients.

Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients.Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients.Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3-94·4) for the low-risk group, and 60% (46·3-71·0) for the high-risk group (hazard ratio [HR] 4·24, 95% CI 2·13-8·47; p0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3-91·8) for the low-risk group, and 57% (42·8-68·5) for the high-risk group (HR 3·63, 1·86-7·01; p0·0001), and in the independent validation set of patients, was 85% (79·6-89·0) for the low-risk group and 54% (46·4-61·1) for the high-risk group (HR 3·70, 2·56-5·35; p0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17-2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer.Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease.Natural Science Foundation of China.

// Zong-Ren Wang 1, 2, * , Jin-Huan Wei 1, * , Jian-Cheng Zhou 3, * , Ahmed Haddad 2, * , Liang-Yun Zhao 4 , Payal Kapur 5 , Kai-Jie Wu 6 , Bin Wang 2 , Yan-Hong Yu 4 , Bing Liao 7 , Da-Lin He 6 , Wei Chen 1 , Vitaly Margulis 2 , Jer-Tsong Hsieh 2 , Jun-Hang Luo 1 1 Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China 2 Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA 3 Department of Urology, Shaanxi Provincial People’s Hospital, Shaanxi, China 4 Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan, China 5 Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA 6 Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China 7 Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China * These authors have contributed equally to this work Correspondence to: Jer-Tsong Hsieh, email: jt.hsieh@utsouthwestern.edu Jun-Hang Luo, email: luojunh@mail.sysu.edu.cn Keywords: DAB2IP, DNA methylation, intratumour heterogeneity, prognosis, renal cell carcinoma Received: October 22, 2015 Accepted: April 02, 2016 Published: April 25, 2016 ABSTRACT We have recently reported tumor suppressive role of DAB2IP in RCC development. In this study, We identified one CpG methylation biomarker (DAB2IP CpG1) located UTSS of DAB2IP that was associated with poor overall survival in a cohort of 318 ccRCC patients from the Cancer Genome Atlas (TCGA). We further validated the prognostic accuracy of DAB2IP CpG methylation by pyrosequencing quantitative methylation assay in 224 ccRCC patients from multiple Chinese centers (MCHC set), and 239 patients from University of Texas Southwestern Medical Center at Dallas (UTSW set) by using FFPE samples. DAB2IP CpG1 can predict the overall survival of patients in TCGA, MCHC, and UTSW sets independent of patient age, Fuhrman grade and TNM stage (all p

Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system., Using molecular markers is a useful way to predict the prognosis of cancer patients. Here, Wei et al. describe a five gene methylation signature that can predict the prognosis of renal clear cell cancer and validate its use in multiple patient cohorts.

It is controversial whether chromophobe renal cell carcinoma (chRCC) or clear cell renal cell carcinoma (ccRCC) is associated with better survival. We conducted a clinical-based cohort study and meta-analysis to evaluate the prognostic role of histology between chRCC and ccRCC. A cohort of 1540 patients (166 with chRCC and 1374 with ccRCC) were selected from Sun Yat-sen University and The Cancer Genome Atlas databases. The clinicopathological parameters and overall survival (OS) were compared between patients with chRCC and those with ccRCC. For the meta-analysis, we searched the PubMed, Cochrane Library, and Ovid databases for studies comparing OS or cancer-specific survival (CSS) between chRCC and ccRCC. The cohort study revealed that patients with chRCC were younger (median 52 vs. 55 years, P

This study was aimed to investigate the potential role of microRNA-29c (miR-29c) in regulating the sensitivities of nasopharyngeal carcinoma (NPC) to ionizing radiation (IR) and cisplatin. Low expression of miR-29c was positively associated with therapeutic resistance in 159 NPC cases. Our further in vitro and in vivo studies illustrated ectopic restoration of miR-29c substantially enhanced the sensitivity of NPC cells to IR and cisplatin treatment by promoting apoptosis. Furthermore, we detected miR-29c repressed expression of anti-apoptotic factors, Mcl-1 and Bcl-2 in NPC tissues and cell lines. These data indicate miR-29c might serve as a potential therapeutic sensitizer in NPC treatment.