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Here, we developed a prostate cancer (PCa) risk nomogram including lymphocyte-to-monocyte ratio (LMR) for initial prostate biopsy, and internal and external validation were further conducted. A prediction model was developed on a training set. Significant risk factors with P < 0.10 in multivariate logistic regression models were used to generate a nomogram. Discrimination, calibration, and clinical usefulness of the model were assessed using C-index, calibration plot, and decision curve analysis (DCA). The nomogram was re-examined with the internal and external validation set. A nomogram predicting PCa risk in patients with prostate-specific antigen (PSA) 4–10 ng ml−1 was also developed. The model displayed good discrimination with C-index of 0.830 (95% confidence interval [CI]: 0.812–0.852). High C-index of 0.864 (95% CI: 0.840–0.888) and 0.871 (95% CI: 0.861–0.881) was still reached in the internal and external validation sets, respectively. The nomogram exhibited better performance compared to the nomogram with PSA only (C-index: 0.763, 95% CI: 0.746–0.780, P < 0.001) and the nomogram with LMR excluded (C-index: 0.824, 95% CI: 0.804–0.844, P < 0.010). The calibration curve demonstrated good agreement in the internal and external validation sets. DCA showed that the nomogram was useful at the threshold probability of >4% and

This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy (NHT) combined with radical prostatectomy (RP) and radiotherapy (RT) administered to patients with high-risk prostate cancer (HRPCa). We searched PubMed, Embase, and the Cochrane Library for studies comparing NHT plus RP or RT with RP or RT alone, administered to patients with HRPCa. We used a random-effects model to compute risk estimates with 95% confidence intervals (CIs) and quantified heterogeneity using the I2 statistic. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. We selected 16 studies. NHT before RP significantly decreased lymph node involvement (risk ratio [RR] = 0.69, 95% CI: 0.56–0.87) and increased the rates of pathological downstaging (RR = 2.62, 95% CI: 1.22–5.61) and organ-confinement (RR = 2.24, 95% CI: 1.54–3.25), but did not improve overall survival and biochemical progression-free survival (bPFS). The administration of NHT before RT to patients with HRPCa was associated with significant benefits for cancer-specific survival (hazard ratio [HR] = 0.51, 95% CI: 0.39–0.68), disease-free survival (HR = 0.51, 95% CI: 0.44–0.60), and bPFS (HR = 0.54, 95% CI: 0.46–0.64). Short-term NHT combined with RT administered to patients with HRPCa conferred significant improvements. Although the advantage of local control was observed when NHT was administered before RP, there was no significant survival benefit associated with HRPCa. Therefore, short-term NHT combined with RT is recommended for implementation in standard clinical practice but not for patients who undergo RP.

In this study, we sequenced a bacteria isolate Pandoraea sp. 892iso isolated from a Phytophthora rubi strain which is an important plant pathogenic oomycete, identified through genome and combined the data with existing genomic data from other 28 the genus of Pandoraea species. Next, we conducted a comparative genomic analysis of the genome structure, evolutionary relationships, and pathogenic characteristics of Pandoraea species. Our results identified Pandoraea sp. 892iso as Pandoraea sputorum at both the genome and gene levels. At the genome level, we carried out phylogenetic analysis of single-copy, gene co-linearity, ANI (average nucleotide identity) and AAI (average amino acid identity) indices, rpoB similarity, MLSA phylogenetic analysis, and genome-to-genome distance calculator calculations to identify the relationship between Pandoraea sp. 892iso and P. sputorum. At the gene level, the quorum sensing genes ppnI and ppnR and the OXA-159 gene were assessed. It is speculated that Pandoraea sp. 892iso is the endosymbiont of the Oomycetes strain of Phytophthora rubi.

The data presented here are related to the article entitled “Comparative analysis of Phytophthora genomes reveals oomycete pathogenesis in crops” [1]. These data contain the description of genomic structure of the two plant pathogens, P. fragariae and P. rubi and characterize several gene families associated with pathogenicity of them: P450, ACX gene families, CAZymes and effector. This data presents the relevant results of two newly sequenced P. fragariae and P. rubi, so as to provide data for further studies by researchers.

The oomycete genus Phytophthora includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined Phytophthora species–P. fragariae and P. rubi. Comparing these Phytophthora species and related genera allowed reconstruction of the phylogenetic relationships within the genus Phytophthora and revealed Phytophthora genomic features associated with infection and pathogenicity. We found that several hundred Phytophthora genes are putatively inherited from red algae, but Phytophthora does not have vestigial plastids originating from phototrophs. The horizontally-transferred Phytophthora genes are abundant transposons that “transmit” exogenous gene to Phytophthora species thus bring about the gene recombination possibility. Several expansion events of Phytophthora gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of Phytophthora evolution and will also be helpful for the design of phytopathological control strategies.

The [-2]proPSA (p2PSA) and its derivatives, the p2PSA-to-free PSA ratio (%p2PSA), and the Prostate Health Index (PHI) have greatly improved discrimination between men with and without prostate cancer (PCa) in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen (tPSA), free PSA, and p2PSA. For each patient, the free-to-total PSA ratio (%fPSA), PSA density (PSAD), p2PSA-to-free PSA ratio (%p2PSA), and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml−1 . Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer (PCa). We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy (RP) and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score (pGS), pathological stage and lymph node involvement (LNI) in RP specimens. Preoperative prostate-specific antigen (PSA) levels, biopsy GS (bGS), and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic (ROC) curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 (95% confidence interval [CI] 1.510-27.010), 3.270 (95% CI: 1.470-7.278) for high levels of TG for pT3-4 disease, and 2.670 (95% CI: 1.134-6.287) for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096-2.545, P= 0.017), and a 1.5-fold increased risk of pT3-4 disease (OR = 1.583, 95% CI 1.106-2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038-2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.

Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b. Phosphorylations of extracellular signal–regulated kinase, p38, and c-Jun NH2-terminal kinase were stimulated by dihydrotestosterone or fibroblast growth factor 8b. Among these major downstream pathways for mitogen-activated protein kinase, c-Jun NH2-terminal kinase signaling was most significantly enhanced. Protein kinase C phosphorylation was higher than AKT by the combined stimulation of dihydrotestosterone and fibroblast growth factor 8b. The phosphorylation of CDC2 was significantly induced by dihydrotestosterone and fibroblast growth factor 8b synergetically, and Smad underwent the same induction as CDC2. So the promoting effect of fibroblast growth factor 8b on cell cycle might contribute to the G2/M transition. This study indicated that the functional interaction between fibroblast growth factor 8b and androgen was essential for the prostate cancer cell proliferation.

Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa.

Previous studies identified an association of low-density lipoprotein (LDL) levels and LDL receptor (LDLR) with renal cell carcinoma (RCC) development. This study investigated the expression and roles of LDLR in RCC. LDLR expression was examined in clear cell RCC (ccRCC) and adjacent normal kidney tissues, and its clinicopathological significance was analyzed. The role of LDLR in RCC cell proliferation, cell cycle, and invasion were assessed in RCC cells with LDLR stable knockdown. LDLR expression was higher in ccRCC tissues than in normal kidney tissues and increased with RCC progression. LDLR knockdown in RCC cells inhibited cell growth, migration and invasion, and induced G1/S cell cycle arrest. We identified an interaction between LDLR and EGFR, and EGFR signaling protein expression was reduced after LDLR knockdown. Our findings reveal that LDLR plays an important role in RCC carcinogenesis, suggesting that LDL and LDLR might be potential targets for therapeutic intervention in RCC. [ABSTRACT FROM AUTHOR]

Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the messenger RNA (mRNA) function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancerfree subjects. Logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs). The association between genetic variants and levels of LDLR mRNA and protein was also evaluated. Compared with the CC genotype, multivariate logistic regression analysis showed that the LDLR rs2738464 variant GG genotype was associated with a significantly decreased ccRCC risk (P = 0.002, OR: 0.605, 95% CI: 0.439-0.833). Further functional experiments showed that the rs2738464 variant G allele affected miR-330 regulation of the LDLR 3′-untranslated region (UTR), increasing LDLR mRNA levels in patient kidney tissues. These findings suggest that LDLR rs2738464 may affect the affinity of miR-330 binding to the LDLR 3′-UTR, thus regulating LDLR expression and contributing to ccRCC risk. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are involved in cancer development and progression. Renal cell carcinoma (RCC) frequently undergoes metastasis and has a high mortality rate. The current study measured miRNA-126 (miR-126) expression levels in 128 pairs of clear cell RCC and adjacent normal kidney tissue samples by reverse transcription-quantitative polymerase chain reaction, and analyzed the association between miR-126 and various clinicopathological parameters. In addition, cell proliferation, wound healing and cell invasion assays were conducted using RCC cells overexpressing miR-126. Potential miR-126 target genes and the signaling pathways that may be regulated by miR-126 were then examined. miR-126 expression was significantly reduced in patients with metastatic RCC compared with patients without metastasis. Consistently, overexpression of miR-126 in RCC cells significantly inhibited cell proliferation, migration and invasion in vitro compared with negative control miRNA. A luciferase reporter assay demonstrated that miR-126 targets Rho associated coiled-coil containing protein kinase 1 (ROCK1) by directly binding the 3'-untranslated region. Furthermore, western blotting identified miR-126 as an important regulator of the AKT and extracellular signal-regulated 1/2 signaling pathways. The results of the present study indicate that miR-126 inhibits RCC cell proliferation, migration and invasion by downregulating ROCK1. These findings suggest that miR-126 may be valuable as a potential target for therapeutic intervention in RCC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the prognostic value of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) in patients with upper urinary tract urothelial carcinoma (UUTUC). Methods: We retrospectively analyzed the clinical data of 140 patients with UUTUC who underwent radical nephroureterectomy from January 2005 to December 2011. We plotted receiver operating characteristic curves of NLR, PLR, and LMR for the diagnosis of tumor recurrence. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Independent risk factor analysis was performed using a Cox proportional hazards regression model. Results: Receiver operating characteristic curves showed that NLR was superior to PLR and LMR as a predictive factor in patients with UUTUC undergoing radical nephroureterectomy. Univariate analysis revealed that NLR (P<0.001 and P<0.001), PLR (P=0.01 and P<0.001), and LMR (P<0.001 and P<0.001) were significantly associated with disease-free survival and progression-free survival (PFS), respectively. Multivariate analysis identified NLR and LMR as independent prognostic factors for disease-free survival (P=0.035 and P=0.002) and PFS (P=0.005 and P=0.002), respectively. Conclusion: NLR and LMR could be independent predictors of disease-free survival and PFS, and NLR is a superior predictive factor to LMR. [ABSTRACT FROM AUTHOR]

Background: Evidence of the association of metabolic syndrome (MetS) with cancer risk is accumulating. However, uncertainties still exist as to the link of MetS with bladder cancer. This study aimed to assess the relationship between MetS and the risk of urothelial carcinoma of the bladder (UC) in a Chinese population. Methods: We retrospectively analyzed clinicopathological data of 972 newly diagnosed UC patients and 1098 cancer-free controls matched to the cases by age and gender. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using unconditional logistic regression in both unadjusted and adjusted models. Results: MetS was not significantly associated with the overall UC risk (p = 0.08). However, a significant association of MetS with UC was observed in female patients (p = 0.006). Diabetes mellitus (crude OR 1.339, 95 % CI 1.079-1.662, p = 0.008; adjusted OR 1.767, 95 % CI 1.308-2.386, p < 0.001) and hypertriglyceridemia (crude OR 1.245, 95 % CI 1.018-1.522, p = 0.033; adjusted OR 1.254, 95 % CI 1.020-1.542, p = 0.032) were significantly associated with UC risk. As the number of MetS components increased, the UC risk was elevated. Having three or more (versus zero) components of MetS was significantly related to risk of overall UC (OR 1.315; 95 % CI 1.006-1.719; p = 0.045) and non-muscle invasive bladder cancer (OR 1.354; 95 % CI 1.019-1.798; p = 0.037). Conclusions: The present study indicated a marginal association between MetS and UC risk, and a significant association with UC risk in female patients. The results need to be evaluated in large-scale prospective cohorts. [ABSTRACT FROM AUTHOR]