Circulating Th22 cells, as well as Th17 cells, are elevated in patients with renal cell carcinoma.

T-helper (Th) 22 cells serve an essential role in different types of tumors and autoimmune diseases. No research has been conducted to study the role of Th22 cells in the pathogenesis of renal cell carcinoma (RCC). We aimed to evaluate the prognostic value of circulating Th22, Th17, and Th1 cells in RCC patients. Thirty-two newly diagnosed RCC patients and thirty healthy controls were enlisted in the research. Their peripheral blood was collected, and the frequencies of circulating Th22, Th17, and Th1 cells were detected by flow cytometry. Plasma IL-22 concentrations were examined by an enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to identify the mRNA expression levels of aromatic hydrocarbon receptor (AHR) and RAR-associated orphan receptor C (RORC) in peripheral blood mononuclear cells (PBMC). Compared with the healthy control group, the frequency of circulating Th22 and Th17 cells and concentrations of plasma IL-22 were significantly increased in RCC patients. However, there was no significant difference in the frequency of Th1 cells. A positive correlation between Th22 cells and plasma IL-22 levels was found in RCC patients. Also, there was a significant positive correlation between Th22 and Th17 cells in RCC patients. An up-regulated expression of AHR and RORC transcription factors were also observed in RCC patients. As tumor stage and grade progressed, the frequencies of Th22 and Th17 cells and the level of plasma IL-22 significantly increased. Meanwhile, there was a positive correlation between Th22 and Th17 cells and RCC tumor stage or grade. Furthermore, patients with high Th22 or Th17 cells frequency displayed a decreased trend in survival rate. Our research indicated that the increased circulating Th22 and Th17 cells and plasma IL-22 may be involved in the pathogenesis of RCC and may be involved in the occurrence and development of tumors. Th22 cells, plasma IL-22, and Th17 cells may be promising new clinical biomarkers and may be used as cellular targets for RCC therapeutic intervention.

Endovascular treatment of spontaneous renal artery dissection.

OBJECTIVE: This study aimed to assess the outcomes of patients with spontaneous renal artery dissection (SRAD) after endovascular repair. METHODS: We performed a retrospective review of SRAD patients after endovascular treatment between January 2007 and August 2018. Demographic, clinical, ancillary testing, treatment, and outcome data were collected and analyzed. RESULTS: Fourteen patients (12 men and 2 women) with a mean age of 47 years were included in this study. All the patients had hypertension, either new onset (78.6%) or pre-existent (21.4%). Sudden flank pain was the most common symptom. Fourteen patients had 15 affected renal arteries. Endovascular repair was successfully performed in 14 arteries. The technical success rate of endovascular repair was 93.3% (14/15), with no postoperative death. Endovascular repair significantly improved hypertension and renal function, and these improvements persisted during the follow-up period. The effective rate of endovascular repair for improving or curing hypertension was 85.7%. Follow-up imaging showed no sign of stent stenosis or occlusion in those patients who received endovascular repair. CONCLUSIONS: Endovascular repair is safe, feasible, and effective for SRAD treatment and should be a promising alternative to open revascularization.

The clinical and biological significance of MICA in clear cell renal cell carcinoma patients.

Major histocompatibility complex class I-related chains A (MICA), a ligand of Natural killer group 2, member D (NKG2D) receptor, is broadly upregulated in epithelial originated tumor cells. MICA plays a critical role in the immune surveillance against tumor cells and is associated with the prognosis of several malignancies. The aim of this study is to evaluate the clinical and biological significance of MICA in clear cell renal cell carcinoma (ccRCC). The expression of MICA was analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Both MICA mRNA and protein levels were upregulated in ccRCC tissues, compared with normal tissues. IHC staining revealed a homogenous pattern of MICA staining within each tumor, which combined both membrane staining and granular cytoplasmic staining. Furthermore, high MICA expression was associated with lymph node metastasis and advanced clinical stage and predicted poor prognosis in patients with ccRCC. Gene set enrichment analysis (GSEA) was performed using RNA-sequencing data from The Cancer Genome Atlas Research Network (TCGA) to elucidate the biological role of MICA in ccRCC and revealed that MICA was significantly associated with the epithelial-to-mesenchymal transition (EMT) gene set, which was further confirmed by qRT-PCR. Our findings contribute to the studies on biomarkers of kidney cancers and the mechanism of renal cancer progression driven by EMT pathway.

Lnc-PLCB1 is stabilized by METTL14 induced m6A modification and inhibits Helicobacter pylori mediated gastric cancer by destabilizing DDX21.

Helicobacter pylori (H. pylori) infection is considered to be an important factor in gastric cancer (GC). Long noncoding RNA (lncRNA) and m6A modification are involved in the occurrence and development of GC, but the role of lncRNA m6A modification in the development of GC mediated by H. pylori is still unclear. Here, we found that H. pylori infection downregulated the expression of lnc-PLCB1 through METTL14-mediated m6A modification and IRF2-mediated transcriptional regulation. Overexpression of lnc-PLCB1 inhibited the proliferation and migration of GC cells, while downregulation of lnc-PLCB1 promoted the proliferation and migration ability of GC cells. In addition, clinical analysis showed that lnc-PLCB1 is lower in GC tissues than in normal tissues. Further study found that lnc-PLCB1 reduced the protein stability of its binding protein DEAD-box helicase 21 (DDX21) and then downregulated the expression of CCND1 and Slug, thereby playing tumour suppressing role in the occurrence and development of GC. In conclusion, the METTL14/lnc-PLCB1/DDX21 axis plays an important role in H. pylori-mediated GC, and lnc-PLCB1 can be used as a new target for GC treatment.

Lack of association between hOGG1 Ser326Cys polymorphism and the risk of bladder cancer: a meta-analysis.

OBJECTIVE: In some but not all studies, hOGG1 Ser326Cys polymorphism has been reported to contribute to the risk of bladder cancer. To determine whether there is a significant association of hOGG1 Ser326Cys polymorphism with the susceptibility for bladder cancer, we performed a comprehensive meta-analysis. METHODS: The electronic PubMed, Medline and Springer databases were searched for publications on the association between hOGG1 Ser326Cys polymorphism and bladder cancer through to May 20, 2011. Seven case-control studies were identified, including 2,474 cases and 2,408 controls. From these identified publications, crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association using fixed- or random-effects models. Two investigators each extracted data and conducted the analysis independently. RESULTS: Overall, no significant associations were found between hOGG1 Ser326Cys polymorphism and bladder cancer in codominant models (GG vs. CC: OR 1.11, 95% CI 0.74-1.66, p = 0.63; GC vs. CC: OR 1.07, 95% CI 0.80-1.41, p = 0.65). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs. GC+CC: OR 1.05, 95% CI 0.65-1.70, p = 0.85), dominant model (GG+GC vs. CC: OR 1.07, 95% CI 0.87-1.32, p = 0.53) and allele model (G vs. C: OR 1.06, 95% CI 0.90-1.26, p = 0.49). In the stratified analyses by ethnicity, control sources, pathology, Hardy-Weinberg equilibrium, significant associations were still not observed. CONCLUSIONS: The overall current literature on hOGG1 Ser326Cys polymorphism and the risk of bladder cancer suggests no statistically significant association between the two. Additional primary studies may be necessary to provide evidence of any significant association between this specific polymorphism and bladder cancer.

Microvessel density and heparanase over-expression in clear cell renal cell cancer: correlations and prognostic significances.

BACKGROUND: Tumor angiogenesis is important in the progression of malignancies, and heparanase plays an important role in sustaining the pathology of clear cell renal cell cancer (ccRCC). The study was carried out to investigate the correlations between microvessel density (MVD) and heparanase expression containing prognostic significances in the patients with ccRCC. METHODS: Specimens from 128 patients with ccRCC were investigated by immunohistochemistry for MVD. RT-PCR and immunohistochemistry were used to detect heparanase expression. Correlations between MVD, heparanase expression, and various clinico-pathological factors were studied. The prognostic significances of MVD and heparanase expression were also analysed. RESULTS: We discovered a statistically significant prevalence of higher MVD in ccRCC compared with adjacent normal renal tissues. MVD was positively correlated with TNM stage and distant metastasis in ccRCC patients, and was also correlated with the expression level of heparanase.Heparanase is over-expressed and correlated with TNM stage, histologic grade, distant metastasis and lymphatic metastasis in ccRCC. High MVD and heparanase over-expression inversely correlate with the survival of ccRCC patients. CONCLUSIONS: Heparanase contributes to angiogenesis of ccRCC and over-expression of heparanase is an independent predictors of prognosis for ccRCC. MVD is correlated with tumor development and metastasis in ccRCC.

HP-1 inhibits the progression of ccRCC and enhances sunitinib therapeutic effects by suppressing EMT.

Trametes robiniophila Murr (Huaier) has been used for many years as an adjuvant treatment for tumors. Sunitinib is the first-line therapy for end-stage renal cancer, but its side effects and drug resistance limit its clinical application. Cell counting kit- 8 (CCK-8), colony formation, scratch, and Transwell assays showed that Huaier polysaccharide (HP-1) reduced tumor progression. Its combination with sunitinib elicited stronger antitumor effects, including induction of apoptosis and cycle arrest. HP-1-induced effects depended on CIP2A downregulation and suppression of the EMT process. Moreover, qPCR and western blotting experiments showed that CIP2A downregulation was particularly pronounced after treatment with the combination therapy and was associated with EMT suppression. In addition, the HP-1/sunitinib combination inhibited the PI3K/Akt/VEGFR pathway, reducing the expression of pathway-related proteins. The HP-1-induced enhancement of sunitinib effects on tumor growth were also observed in vivo in a xenograft mouse model. Overall, these results indicated that HP-1 exerted antitumor effects against clear cell renal cell carcinoma (ccRCC) and enhanced the therapeutic efficacy of sunitinib.

A polysaccharide from Huaier ameliorates cisplatin nephrotoxicity by decreasing oxidative stress and apoptosis via PI3K/AKT signaling.

Cisplatin (CP), a common chemotherapy drug used in treatment of malignant tumors. Due to various side effects such as nephrotoxicity (kidney damage), it's efficiency and therapeutic application are limited. This study focuses on finding a suitable drug that would attenuate the side effects like kidney damage, caused by CP. Huaier polysaccharide (HP-1), an extraction of Trametes robiniophila Murr, with a molecular weight of 3 × 104 Da. Previous studies have shown that HP-1, exhibits anti-tumor potential and immunomodulatory effects. We hypothesized that HP-1 has the effect of attenuating the nephrotoxicity caused by CP chemotherapy and protecting renal function. Through our experiments, we observed that HP-1 can attenuate the level of oxidative stress, inflammation and mitochondrial dysfunction, thereby reducing kidney damage. In vitro, we observed that HP-1 significantly inhibits CP-induced renal tubular cell apoptosis and cell cycle arrest. In addition, HP-1 also affects the expression level of the protein by regulating the PI3K/Akt/mTOR signaling pathway and thus attenuates the side effects induced by cisplatin. Therefore, HP-1 may be a potential drug for preventing CP-induced renal damage.

Downregulation of eukaryotic translation initiation factor 3b inhibited proliferation and metastasis of gastric cancer.

Eukaryotic translation initiation factor 3 (eIF3) plays an important role in the regulation of mRNA translation, cell growth and cancer development. eIF3b is the main scaffolding subunit in the eIF3 complex and has been demonstrated to contribute to the development of several cancers. First, our study found that the downregulation of eIF3b could inhibit the proliferation and metastasis of gastric cancer cells by regulating the expression of cancer-related genes. In addition, the expression of eIF3b correlated with the stage and progression of gastric cancer and was shown to be upregulated in human chronic gastritis and in gastric cancer tissues compared with the expression of eIF3b in normal gastric tissues. Moreover, Helicobacter pylori (H. pylori) infection could upregulate the expression of eIF3b in gastric cancer cells, suggesting that eIF3b might be involved in the carcinogenic process of H. pylori. The above findings identified the oncogenic role of eIF3b in gastric cancer development, and this may contribute to the exploration and discovery of novel therapeutic targets for gastric cancer treatment.

CIP2A Promotes Proliferation, Invasion and Chemoresistance to Cisplatin in Renal Cell Carcinoma.

CIP2A is a well-known oncoprotein whose expression is elevated in multiple human solid tumor types. However, its role in renal cell carcinoma (RCC) development is poorly understood. Thus, in our present study, we used the renal cancer cell lines 786-O, A498 and CAKI-1 and the renal epithelial cell line HK-2 to clarify the function of CIP2A in RCC. We found that CIP2A expression is much higher in the RCC cells than in the normal renal epithelial cell. Lentivirus covered coding region CIP2A cDNA sequence and CIP2A siRNA were used to up and down regulate CIP2A expression in vitro. We found that overexpression of CIP2A promoted G1/S transition and cell proliferation. In addition, up-regulation of CIP2A significantly enhanced the invasion and migration capabilities of the cells. Furthermore, CIP2A promoted epithelial-mesenchymal transformation (EMT) and chemoresistance to cisplatin in RCC cells. Taken together, our findings demonstrate that CIP2A plays an important role in proliferation, invasion and chemoresistance to cisplatin in RCC cells. CIP2A may serve as an ideal molecular target for RCC therapeutics.

MiRNA-491-5p inhibits cell proliferation, invasion and migration via targeting JMJD2B and serves as a potential biomarker in gastric cancer.

Our previous work discovered that the histone demethylase JMJD2B (KDM4B) plays oncogenic roles in gastric carcinogenesis, but the regulatory mechanism of JMJD2B in gastric cancer has not been well defined. It has been revealed that microRNAs function as gene regulators by binding to the 3'UTR of mRNAs to inhibit gene expression. In this study, we found that miR-491-5p suppressed cell proliferation, invasion and migration by directly targeting the JMJD2B 3'UTR in gastric cancer. Moreover, miR-491-5p was decreased in GC tissues compared with adjacent normal tissues, and JMJD2B had the inverse expression pattern. In contrast to healthy individuals, GC patients had lower miR-491-5p expression in serum (P<0.0001). Our data indicate that miR-491-5p serves as a tumor suppressor in GC and might be a novel potential biomarker for the detection of gastric cancer.

Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions.

Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively. The necrotic rate and apoptotic rate in the EPS exposure group were significantly higher than these rates noted in the control group as revealed by LDH release assay and Hoechst 33342/ PI double staining, respectively. At the concentration of 1.0 mg/ml, the necrotic and apoptotic rates reached 41.7±6.6 and 7.8±1.4%, respectively (P<0.01). However, the fluorescence intensity of intracellular calcium concentration ([Ca2+]i) was markedly elevated from 0.029±0.0007 to 0.060±0.003 (P<0.001) after the intervention of EPS. Moreover, the fluorescence intensity of intracellular ROS in the EPS exposure group was significantly higher (0.074±0.005) compared to that observed in the control group (0.033±0.001, P<0.001), which was partly attenuated by the specific antioxidant N-acetylcysteine (NAC). Furthermore, our results demonstrated that EPS significantly downregulated the expression of SIRT-1 and obviously induced the dephosphorylation of mTOR. Moreover, combined treatment with the SIRT-1 inhibitor nicotinamide and EPS was able to significantly enhance the induction of necrosis and reduction in cell viability of 786-O cells noted following treatment with EPS alone. In summary, we conclude that EPS induced the death of 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions, which provide novel insight into the application of natural plant extracts for the treatment of cancers.

Erythrocytosis caused by giant chromophobe renal cell carcinoma: a case report indicating a 9-year misdiagnosis of polycythemia vera.

BACKGROUND: Erythrocytosis, a rare paraneoplastic syndrome, generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma. CASE PRESENTATION: We report a case of a young man suffering from a giant (22-cm) mass on his left kidney. Because of a history of polycythemia vera, the patient had been treated for the condition for 9 years. Radical nephrectomy was successfully performed, and the postoperative pathologic examination confirmed a diagnosis of chromophobe renal cell carcinoma. Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma. CONCLUSIONS: Chromophobe renal cell carcinoma could cause erythrocytosis, but the clear-cut mechanism needs further research. Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

Pretreatment Serum Cystatin C Levels Predict Renal Function, but Not Tumor Characteristics, in Patients with Prostate Neoplasia.

To evaluate the role of Cystatin C (Cys-C) in tumorigenesis and progression of prostate cancer (PCa), we retrospectively collected the clinical information from the records of 492 benign prostatic hyperplasia (BPH), 48 prostatic intraepithelial neoplasia (PIN), and 173 PCa patients, whose disease was newly diagnosed and histologically confirmed. Pretreatment serum Cys-C levels were compared across the various groups and then analyzed to identify relationships, if any, with clinical and pathological characteristics of the PCa patient group. There were no significant differences in serum Cys-C levels among the three groups (P > 0.05). In PCa patients with normal SCr levels, patient age was correlated with serum Cys-C level (P ≤ 0.001) but did not correlate with alkaline phosphatase (AKP), lactate dehydrogenase (LDH), prostate specific antigen (PSA), Gleason score, or bone metastasis status (P > 0.05). Age and SCr contributed in part to the variations in serum Cys-C levels of PCa patients (r = 0.356, P ≤ 0.001; r = 0.520, P ≤ 0.001). In conclusion, serum Cys-C levels predict renal function in patients with prostate neoplasia, but were not a biomarker for the development of prostate neoplasia, and were not correlated with the clinicopathological characteristics of PCa.

Eukaryotic Translation Initiation Factor 3b is both a Promising Prognostic Biomarker and a Potential Therapeutic Target for Patients with Clear Cell Renal Cell Carcinoma.

Eukaryotic translation initiation factors (eIFs) constitute a new class of therapeutic cancer targets. EIF3b is the major scaffold protein of eIF3 (the largest core of eIFs). We sought to define the role played by and the mechanism of action of eIF3b in patients with clear cell renal cell carcinoma (ccRCC). We found that high-level eIF3b expression in tumors was not only associated with an aggressive tumor phenotype, but was also independently prognostic for patients with ccRCC. Knockdown of eIF3b impaired the action of the Akt pathway, thus inhibiting cell proliferation by disrupting the cell cycle and triggering apoptosis. Furthermore, the epithelial-to-mesenchymal transition was impaired after eIF3b depletion, via suppression of cell migration and invasion. Additionally, eIF3b knockdown significantly inhibited the growth of subcutaneous xenografts in mice. Together, these data show that eIF3b is both a promising prognostic biomarker and a potential therapeutic target for patients with ccRCC.

JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression.

Helicobacter pylori (H. pylori) infection is the strongest risk factor for the initiation and progression of gastric cancer. However, the mechanism of H. pylori-induced pathogenesis remains unclear. In this study, we investigate the role of H. pylori infection in JMJD2B upregulation and the mechanism underlying gastric carcinogenesis. We find that JMJD2B can be induced by H. pylori infection via ß-catenin pathway. ß-catenin directly binds to JMJD2B promoter and stimulates JMJD2B expression following H. pylori infection. Increased JMJD2B, together with NF-κB, binds to COX-2 promoter to enhance its transcription by demethylating H3K9me3 locally. JMJD2B and COX-2 expression is upregulated in H. pylori infected mice in vivo. Furthermore, JMJD2B and COX-2 expression is gradually increased in human gastric tissues from gastritis to gastric cancer. The level of JMJD2B and COX-2 in H. pylori-positive gastritis tissues is significantly higher than that in H. pylori-negative tissues. Moreover, a positive correlation between JMJD2B and COX-2 expression is found in both gastritis and gastric cancer tissues. Therefore, JMJD2B is a crucial factor in triggering H. pylori-induced chronic inflammation and progression of gastric carcinogenesis and it may serve as a novel target for the intervention of gastric cancer.

Cytoplasmic expression of pontin in renal cell carcinoma correlates with tumor invasion, metastasis and patients' survival.

Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. Distant metastasis represents the major cause of death in patients with RCC. Recent studies have implicated the AAA+ ATPase pontin in many cellular activities that are highly relevant to carcinogenesis. In this study, we demonstrate for the first time that pontin was up-regulated in RCC, and plays a previously unknown pro-invasive role in the metastatic progression of RCC through epithelial-to-mesenchymal transition (EMT) pathway. 28 pairs of freshly frozen clear cell RCC samples and the matched normal renal tissues analyzed by quantitative RT-PCR and western blotting demonstrated that pontin was up-regulated in clear cell RCC tissues than in normal renal tissues. In addition, immunohistochemistry was used to evaluate subcellular pontin expression in 95 RCC patients, and found that overexpression of pontin in cytoplasm positively correlated with the metastatic features, predicting unfavorable outcomes of RCC patients. Furthermore, in vitro experiments show pontin was predominantly expressed in cytoplasm of RCC cell lines, and a significant suppression of cell migration and invasion in pontin siRNA treated RCC cell lines was observed. Mechanistic studies show that pontin depletion up-regulated the E-cadherin protein and down-regulated vimentin protein, and decreased nuclear ß-catenin expression, suggesting the involvement of EMT in pontin induced metastatic progression. Together, our data suggest pontin as a potential prognostic biomarker in RCC, and provide new promising therapeutic targets for clinical intervention of kidney cancers.

Meta-analysis of the urokinase gene 3'-UTR T/C polymorphism and susceptibility to urolithiasis.

Urokinase is involved in the processes of initiating urinary stones. Several published case-control studies have examined the relationship of urokinase gene 3'-untranslated region (3'-UTR) T/C polymorphism and urolithiasis, but yielded inconsistent findings. In this study, a comprehensive meta-analysis was conducted by pooling relevant studies to obtain reliable conclusions. Studies focusing on the association between urokinase gene 3'-UTR T/C polymorphism and urolithiasis were retrieved through PubMed, Medline, Web of Science and the China National Knowledge Infrastructure platform without any limit on language, until October 2012. Four independent articles were eventually identified as eligible for the final meta-analysis, involving 1,195 subjects. Crude odds ratios (ORs), as well as 95% confidence intervals (CIs), were assessed for the association by either fixed- or random-effects models using RevMan 5.0 software. Significant associations were noted in the 'TC vs. CC' codominant model for total population (OR=2.53; 95% CI, 1.43-4.46; P=0.001), Asian population (OR=2.46; 95% CI, 1.38-4.40; P=0.002), male (OR=2.98; 95% CI, 1.43-6.21; P=0.004), Hardy-Weinberg equilibrium (HWE) (OR=2.46; 95% CI, 1.38-4.40; P=0.002) and recurrence (OR=2.66; 95% CI, 1.51-4.67; P=0.00). Statistically significant associations were also observed in the 'TT+TC vs. CC' dominant model for the Asian, male, HWE and recurrence population (P<0.05). Additionally, a significant difference was detected in the 'T vs. C' allele model for HWE. However, there were no associations in either the 'TT vs. CC' codominant model or 'TT vs. TC+CC' recessive model. In conclusion, the present meta-analysis suggests that urokinase gene T allele may increase the susceptibility of urolithiasis.

Association between HIF1A P582S and A588T polymorphisms and the risk of urinary cancers: a meta-analysis.

PURPOSE: The hypoxia-inducible factor-1 alpha (HIF1A) plays a vital role in cancer initiation and progression. Previous studies have reported the existence of HIF1A P582S and A588T missense polymorphisms in renal, urothelial and prostatic carcinomas, however the effects remain conflicting. Therefore, we performed a meta-analysis to assess the association between these sites and the susceptibility of urinary cancers. METHODS: We searched the PubMed database without limits on language until Nov 25, 2012 for studies exploring the relationship of HIF1A P582S and A588T polymorphisms and urinary cancers. Still, article search was supplemented by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the associations between the two by RevMan 5.0 software. Simultaneously, publication bias was estimated by funnel plot and Begg's test with Stata 12.1 software. RESULTS: Overall, 11 individual case-control studies with 5195 cases and 5786 controls for P582S polymorphism, and 9 studies with 3482 cases and 4304 controls for A588T polymorphism were respectively included in the final meta-analysis. For HIF1A P582S polymorphism, individuals with TT genotype showed 1.60 fold higher risk than the others carrying CT or CC genotypes in Caucasian population (OR = 1.60, 95% CI = 1.09-2.33, P(heterogeneity )= 0.11, P = 0.02). For HIF1A A588T polymorphism, the A allele was significantly correlated with higher urinary cancers risk in Asian population (OR = 1.41, 95% CI = 1.03-1.93, P(heterogeneity) = 0.22, P = 0.03). Still, significant associations were found for prostate cancer in the allele and dominant models (OR = 1.46, 95% CI = 1.01-2.12, P(heterogeneity )= 0.49, P = 0.04 and OR = 1.45, 95% CI = 1.00-2.12, P(heterogeneity) = 0.50, P = 0.05). CONCLUSIONS: The current findings suggest that HIF1A P582S polymorphism correlates with urinary cancers risk in Caucasian population, while A588T polymorphism may increase the risk of urinary cancers in Asian population and prostate cancer.

Upregulation of nucleus HDGF predicts poor prognostic outcome in patients with penile squamous cell carcinoma bypass VEGF-A and Ki-67.

Hepatoma-derived growth factor (HDGF) has been verified to serve as a credible prognostic marker for several types of cancers, but its role in urologic carcinomas remains undetermined. In this study, we analyzed the significance of HDGF, as well as its relative factors such as vascular endothelial growth factor-A (VEGF-A) and Ki-67, in penile squamous cell carcinoma (PSCC). Formalin-fixed paraffin-embedded PSCC samples from 54 patients receiving surgery at Qilu Hospital of Shandong University were included in the retrospective study. The expressions of HDGF, VEGF-A, and Ki-67 were detected by immunohistochemistry of a non-biotin polymerized horseradish peroxidase method. The relationships between the expressions of HDGF and VEGF-A, Ki-67 were assessed. Moreover, their correlations with clinical pathologic characteristics and disease prognosis were, respectively, evaluated. HDGF, VEGF-A, and Ki-67 were positively expressed in 28 (51.9%), 29 (53.7%), and 26 (48.1%) patients, respectively. The expressions of VEGF-A and Ki-67 were closely correlated with PSCC type (P < 0.05). A statistically significant relationship between the expressions of HDGF and VEGF-A in PSCC was observed (P = 0.03). Patients with symptom interval of more than 6 months had a significantly poorer survival rate than those with symptom interval less than 6 months (43.3 vs. 70.8%, P = 0.043). Patients with positive HDGF expression also showed a significantly poorer survival rate than those with negative HDGF expression (39.3 vs. 73.1%, P = 0.013). Logistic regression demonstrated that the expression level of HDGF was an independent predictor for the prognosis of postoperative patients. The expression of HDGF significantly correlated with VEGF-A, but not Ki-67 expression. Overexpression of HDGF, rather than VEGF-A or Ki-67, was confirmed to be an independent prognosticator of poor outcome for PSCC patients.