[Show abstract][Hide abstract] ABSTRACT: The involvement of circulating microRNAs (miRNAs) in cancer and their potential as diagnostic and prognostic biomarkers are becoming increasingly known. However, the significance of circulating miRNAs in upper tract urothelial carcinoma (UTUC) has remained to be investigated. The present study performed a genome‑wide serum miRNA analysis using a deep sequencing platform for initial screening. Subsequently, serum samples of 46 UTUC patients and 30 cancer‑free individuals with hematuria were subjected to a quantitative reverse‑transcription polymerase chain reaction analysis. The expression of thirteen miRNAs (miR‑664a‑3p, miR‑423‑5p, miR‑431‑5p, miR‑191‑5p, miR‑92a‑3p, miR‑22‑3p, miR‑26a‑5p, miR‑33b‑3p, miR‑16‑5p, let‑7a‑5p, let‑7b‑5p, let‑7f‑5p and let‑7c) was significantly different in serum from UTUC patients compared with that in control samples. Receiver operator characteristic analysis showed that 10 miRNAs (miR‑664a‑3p, miR‑431‑5p, miR‑423‑5p, miR‑191‑5p, miR‑33b‑3p, miR‑26a‑5p, miR‑22‑3p, miR‑16‑5p, let‑7b‑5p and let‑7c) had the potential to distinguish individuals with UTUC from the controls (areas under the curve >0.8). The present study provided the first evidence for the potential use of circulating miRNAs as biomarkers for UTUC diagnosis, which remains to be verified by further studies.
Molecular Medicine Reports 08/2015; 12(5). DOI:10.3892/mmr.2015.4257 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aberrant microRNAs (miRNAs) are reported to contribute to the pathogenesis of most human malignancies. The miRNA, miR-134, has been found to be downregulated in renal cell carcinoma (RCC), but its function in the disease is unknown. The aims of this study were to detect the expression of miR-134 in human RCC samples and explore its function in RCC cell lines. Real-time qualitative polymerase chain reaction (qPCR) was used to quantify miR-134 in human RCC samples. Assays for cell cycle, viability, migration, and invasion were performed to assess the phenotypic changes in RCC cells. A luciferase reporter assay was carried out to confirm whether KRAS (Kirsten rat sarcoma viral oncogene homolog) is a direct target of miR-134. Western blot was used to identify the potential signaling pathways that had an impact on RCC cell growth and alterations of markers for epithelial-mesenchymal transition (EMT), which affected metastasis by miR-134. miR-134 was found to be downregulated in RCC samples (p<0.05), while overexpression of miR-134 suppressed proliferation (p<0.05) by triggering G1/G0 cell cycle arrest (p<0.05). Forced expression of miR-134 could also inhibit migration (p<0.05) and invasion (p<0.05) by blocking EMT in RCC cell lines. KRAS was identified as a target of miR-134, and miR-134 may act as a tumor suppressor through the KRAS-related MAPK/ERK pathway other than PI3K/AKT signaling. Thus, miR-134 may function as a tumor suppressor in cell proliferation and EMT by targeting KRAS in RCC cells.
DNA and cell biology 03/2015; 34(6). DOI:10.1089/dna.2014.2629 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Radical nephrectomy with inferior vena cava (IVC) thrombectomy is the preferred treatment for renal cell carcinoma (RCC) with IVC thrombus. However, IVC thrombectomy using a laparoscopic approach has not been reported for high-level thrombi.
To describe the surgical technique for laparoscopic IVC thrombectomy in patients with different thrombus levels and to assess its safety and feasibility.
Design, setting, and participants:
Retrospective review of medical records for 11 patients with right-side RCC, including six patients with level II IVC thrombus and five patients with level IV thrombus.
Laparoscopic thrombectomy for level II thrombus was performed after clamping the infrarenal IVC, left renal vein, and infrahepatic IVC. Laparoscopic thrombectomy and thoracoscope-assisted open atriotomy for level IV thrombus were performed after establishing cardiopulmonary bypass and clamping the infrarenal IVC, left renal vein, and hepatoduodenal ligament.
The intraoperative variables, postoperative complications, and surgical outcomes were assessed.
Results and limitations:
The median operative time was 210min. The median IVC clamping time for patients with level II and level IV thrombus was 16.5 and 31min, respectively. The median estimated blood loss was 510ml, and no major intraoperative or postoperative complications occurred. One patient with level IV thrombus died of brain metastasis 6 mo after the operation, and the remaining ten patients had no local recurrence or distant metastasis during a median follow-up period of 31 mo.
Laparoscopic IVC thrombectomy for level II thrombus and well-selected level IV thrombus may be a safe and technically feasible alternative to open surgery.
We studied the treatment of patients with an inferior vena cava thrombus at different levels using a laparoscopic approach. This technique was safe and feasible in well-selected patients.
European Urology 12/2014; 68(1). DOI:10.1016/j.eururo.2014.12.011 · 13.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Raf-1 kinase inhibitor protein (RKIP) plays a critical role in tumor development by regulating cell functions such as invasion, apoptosis and differentiation. Down-regulation of RKIP expression has been implicated in the development and progression of renal cell carcinoma (RCC). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC.
A total of 5 tagging single-nucleotide polymorphisms (tSNPs) in RKIP were selected and genotyped by SNapShot method in a case-control study of 859 RCC patients and 1004 controls. The logistic regression was used to evaluate the genetic association with occurrence and progression of RCC. The functionality of the important SNP was preliminary examined by qRT-PCR.
We found that the rs17512051 in the promoter region of RKIP was significantly associated with decreased clear cell RCC (ccRCC) risk (TA/AA vs. TT: P = 0.039, OR = 0.78, 95%CI = 0.62–0.99). Another SNP (rs1051470) in the 3′UTR region of RKIP was marginally associated with increased ccRCC risk (TT vs. CC+CT: OR = 1.45, 95%CI = 1.01–2.09). In the stratified analysis, the protective effect of rs17512051 was more predominant in the subgroups of male, non-smokers, non-drinkers as well as subjects without history of diabetes. Furthermore, we observed higher RKIP mRNA levels in the presence of the rs17512051A allele in normal renal tissues.
Our results suggest that the potentially functional RKIP rs17512051 polymorphism may affect ccRCC susceptibility through altering the endogenous RKIP expression level. Risk effects and the functional impact of this polymorphism need further validation.
PLoS ONE 10/2014; 9(10):e109285. DOI:10.1371/journal.pone.0109285 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To evaluate the role of combined computed tomography (CT) arteriography (CTA), venography, and urography in laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping.
Materials and methods:
Seventy-five patients underwent laparoscopic partial nephrectomy with segmental renal artery clamping. Three-dimensional (3D) CTA, CT venography, and CT urography models were reconstructed and combined before surgery. Surgeries were performed using these 3D models for surgical orientation.
All procedures were performed successfully without conversion to main renal artery clamping. The mean operative time was 82.6 minutes, and the mean clamping time of target arteries was 20.3 minutes. Grade-I and grade-II complication rates were 5.3% and 5.3%, respectively. Compared to orientation with CTA alone, the use of the combined 3D model resulted in a modification of the planned hilar approach for target dissection in 18 cases (24%). Tumor location correlated with modification of the planned hilar approach. Lower pole tumors were treated with a modification of the hilar approach 58.3% of the time, and 37.5% of striding tumors were treated with a modified approach (P = .001). Only 11.1% of anterior tumors and no posterior or upper pole tumors underwent modification of the hilar approach after evaluation with the combined 3D model. Tumor size and tumor growth pattern did not affect the distribution of approach modifications (P = .89 and P = .52).
The combined 3D model seems to facilitate target artery orientation and surgical dissection. The combined model may alter the surgical approach used for some lower pole or striding renal tumors compared to the approach suggested by conventional CTA.
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is fundamentally important to the pathogenesis of clear cell renal cell carcinoma (ccRCC). We investigated the association between variations of genes related to angiogenesis and the risk of ccRCC. In a case-control study of 859 ccRCC patients and 1004 cancer-free subjects, we genotyped 24 potentially functional single nucleotide polymorphisms (SNPs) in seven angiogenesis-related genes (HIF1A, EPAS1, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) using the TaqMan or Snapshot method. Unconditional logistic regression, adjusted for potential confounding factors, was used to assess the risk associations. The functionality of selected SNPs was assessed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and luciferase reporter gene assays. We found two SNPs (VEGFA rs2010963 and VEGFR3 rs448012) that were significantly associated with increased risk of ccRCC, after adjusting for multiple comparisons [rs2010963 CC/GC cf. GG: false discovery rate (FDR) = 0.048, odds ratio (OR) = 1.36, 95% confidence interval (95% CI) = 1.12-1.66; rs448012 CC/GC cf. GG: FDR = 0.048, OR = 1.38, 95% CI =1.13-1.69]. Real-time quantitative PCR revealed that the variant genotypes of rs2010963, but not rs448012, were associated with increased gene expression in normal tissues of ccRCC patients (CC/GC cf. GG: P = 0.036). The luciferase reporter assay showed that the rs2010963 C allele significantly increased luciferase activity over that of the rs2010963 G allele. Our results indicate that VEGFA rs2010963 and VEGFR3 rs448012 are associated with risk of ccRCC. Furthermore, rs2010963 is a functional SNP that may affect ccRCC susceptibility by modulating endogenous VEGFA expression.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To describe the feasibility of retroperitoneal laparoscopic reimplantation of the left renal vein (LRV) for nutcracker syndrome (NCS).
Patients and methods:
Two patients with NCS underwent the surgery. Both patients complained of gross hematuria and flank discomfort that could not be relieved by resting. They were placed in a supine position and 5 ports were placed in the right abdominal wall. The procedures were performed with a retroperitoneal approach. The LRV was transected and then reimplanted into the distal inferior vena cava.
The procedures were performed successfully without any major complications. The total operation time was 105 and 120 min, respectively. Hematuria and flank discomfort were resolved after the surgery. Ultrasonography revealed a patent lumen without compression.
Retroperitoneal laparoscopic reimplantation of the LRV appears to be a feasible procedure with satisfactory short-term outcomes.
Urologia Internationalis 08/2014; 94(1). DOI:10.1159/000362423 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Over the past two decades, the clinical presentation of renal masses has evolved, where the rising incidence of small renal masses (SRMs) and concomitant minimal invasive treatments have led to noteworthy changes in paradigm of kidney cancer. This study was to perform a proportional meta-analysis of observational studies on perioperative complications and oncological outcomes of partial nephrectomy (PN) and radiofrequency ablation (RFA).
The US National Library of Medicine's life science database (Medline) and the Web of Science were exhaustly searched before August 1, 2013. Clinical stage 1 SRMs that were treated with PN or RFA were included, and perioperative complications and oncological outcomes of a total of 9 565 patients were analyzed.
Patients who underwent RFA were significantly older (P < 0.001). In the subanalysis of stage T1 tumors, the major complication rate of PN was greater than that of RFA (laparoscopic partial nephrectomy (LPN)/robotic partial nephrectomy (RPN): 7.2%, open partial nephrectomy (OPN): 7.9%, RFA: 3.1%, both P < 0.001). Minor complications occurred more frequently after RFA (RFA: 13.8%, LPN/RPN: 7.5%, OPN: 9.5%, both P < 0.001). By multivariate analysis, the relative risks for minor complications of RFA, compared with LPN and OPN, were 1.7-fold and 1.5-fold greater (both P < 0.01), respectively. Patients treated with RFA had a greater local progression rate than those treated by PN (RFA: 4.6%, LPN/RPN: 1.2%, OPN: 1.9%, both P < 0.001). By multivariate analysis, the local tumor progression for RFA versus LPN/RPN and OPN were 4.5-fold and 3.1-fold greater, respectively (both P < 0.001).
The current data illustrate that both PN and RFA are viable strategies for the treatment of SRMs. Compared with PN, RFA showed a greater risk of local tumor progression but a lower major complication rate, which is considered better for poor candidates. PN is with no doubt the golden treatment for SRMs, and LPN has been widely accepted as the first option for nephron-sparing surgery by experienced urologists. RFA may be the best option for select patients with significant comorbidity.
Chinese medical journal 07/2014; 127(13):2497-503. DOI:10.3760/cma.j.issn.0366-6999.20132779 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Recent large-scale transcriptome analyses have found large numbers of transcripts, including that of long non-coding RNAs (lncRNAs), which are aberrant in various diseases, especially cancers. However, it is not clear whether lncRNAs are involved specifically in renal cell carcinoma (RCC). We investigated the expression patterns of lncRNAs in five RCC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via microarray.
A microarray with 33,045 lncRNA probes and 30,215 mRNA probes was used to identify deregulated lncRNAs in five RCC patients. Furthermore, we confirmed the relative expression levels of AK096725 and ENST00000453068 in 70 paired samples by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
The lncRNA microarray revealed 27,279 lncRNAs in RCC samples, of which 480 were significantly upregulated (P<0.05; T/N>1.5) and 417 were significantly downregulated (P<0.05; N/T>1.5) compared with the matched non-tumor samples. In addition, 19,995 mRNAs were detected, of which 458 were significantly upregulated (P<0.05; T/N>1.5) and 413 were significantly downregulated (P<0.05; N/T>1.5). The expression level changes of AK096725 (P = 0.043) and ENST00000453068 (P<0.001) in 70 paired samples were in accord with the microarray data.
The study uncovered expression patterns of lncRNAs in 5 RCC patients, as well as a number of aberrant lncRNAs and mRNAs in tumor samples compared with the non-tumor tissues. The revelation of an association between AK096725 expression and RCC is especially noteworthy. These findings may help to find new biomarkers in RCC.
PLoS ONE 06/2014; 9(6):e99372. DOI:10.1371/journal.pone.0099372 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to evaluate the feasibility and clinical significance of using a modified liver-mobilization technique to treat renal cell carcinoma (RCC) combined with intrahepatic inferior vena cava (IVC) thrombosis.
A total of 11 level III thrombus patients underwent radical nephrectomy with resection of the tumor thrombus from intrahepatic IVC. A father clamp was used in combination with hepatic portal blocking to control the IVC.
The intraoperative mortality and postoperative complications were reduced in 11 cases of RCC with intrahepatic IVC thrombosis. The mean blood loss was 800 mL, and mean patient hospital stay was 13 days. Follow-up was conducted for one to four months, with only two cases of recurrence recorded.
The proposed modified liver-mobilization technique could safely and effectively treat RCC and reduce intrahepatic IVC thrombosis.
World Journal of Surgical Oncology 04/2014; 12(1):131. DOI:10.1186/1477-7819-12-131 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Erythropoietin (EPO) is a circulating glycosylated protein hormone and has been implicated in the development and progression of non-hematopoietic tissue tumors. The objective of the present study was to determine if the EPO rs576236 polymorphism was associated with the risk of adrenal tumors. We genotyped the EPO rs576236 polymorphism in a case-control study of 288 adrenal tumor patients and 456 cancer-free controls by using the TaqMan method, and assessed the association between the polymorphism and the adrenal tumor risk by logistic regression. Furthermore, 95% confidence interval (CI) was used to assess the genetic association between the polymorphism and the risk of adrenal tumor. Compared with the TT genotype, the TC genotype had a significantly increased risk of adrenal tumor [adjusted odds ratio (OR) = 1.24, 95% CI = 1.12-2.22]. Furthermore a significantly increased risk of adrenal tumor was found in the combined variant genotypes TC+CC compared with the TT genotype (adjusted OR = 1.17, 95% CI = 1.12-2.21). Our present study suggests that the rs576236 polymorphism of EPO confers susceptibility to adrenal tumor in the Chinese population.
The Journal of Urology 04/2014; 191(4):e14. DOI:10.1016/j.juro.2014.02.130 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To report our initial experience in treating renal nutcracker syndrome by retroperitoneal laparoscopic extravascular stenting.
Patients and methods:
Two male patients, aged 13 and 16 years, were diagnosed with nutcracker syndrome and received retroperitoneal laparoscopic extravascular stent placement. The perioperative data were collected and evaluated. The follow-up was 10 and 18 months.
Both procedures were successful without obvious complications. Total operative time was 65 and 50 min, estimated blood loss was 110 and 70 ml, and postoperative hospital stay was 4 and 6 days. The symptom of gross hematuria ceased 3 and 6 days after surgery. Both patients had normal findings during follow-up.
Treatment of nutcracker syndrome by retroperitoneal laparoscopic extravascular stent placement is a safe and feasible procedure, especially for youngsters in the period of physical development. Longer follow-up and further experience are needed to evaluate the efficacy of this procedure.
Urologia Internationalis 02/2014; 92(4). DOI:10.1159/000353349 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are members of the insulin-like growth factor (IGF) family that play important roles in carcinogenesis. We hypothesized that the functional polymorphisms in IGF-I and IGFBP-3 may be associated with the risk of prostate cancer (PCa) in the Chinese population. This hospital-based case-control study included 664 PCa patients and 702 cancer-free controls. Nine SNPs in IGF-I and IGFBP-3 were genotyped using the TaqMan assay. The genetic associations between the pathogenesis and progression of PCa were assessed by logistic regression. We found that the genotype and allele frequency distribution of rs6218, rs35767 and rs5742612 were significantly different when comparing PCa cases to controls (P = 0.005, 0.005 and 0.020, respectively). In the combined analysis, individuals with 2-6 risk alleles had an elevated risk of PCa compared to those with 0-1 risk alleles. We also found that the association between the combined risk alleles and the risk of PCa appeared stronger in the following subgroups: individuals older than 71 years of age (OR = 1.41, 95%CI = 1.05-1.91, P = 0.020), nonsmokers (OR = 1.68, 95%CI = 1.21-2.32, P = 0.002), nondrinkers (OR = 1.32, 95%CI = 1.02-1.61, P = 0.002), and those with a negative family history of PCa (OR = 1.28, 95%CI = 1.02-1.71, P = 0.022). Our results indicate that the three SNPs (rs6218, rs35767 and rs5742612) and the joint genotypes with 2-6 risk alleles, may contribute to the susceptibility to PCa, but not the progression, in the Chinese population.
PLoS ONE 02/2014; 9(2):e85609. DOI:10.1371/journal.pone.0085609 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.
[Show abstract][Hide abstract] ABSTRACT: In most hospitals, several options for the management of renal stones are available: shockwave lithotripsy, endourologic treatment, or surgery. Choice of treatment is based on the anatomic characteristics of the patient, and the location and size of the stones. In this study we assessed a retroperitoneal laparoscopic technique for treatment of complex renal stones.
Seventy-five patients, including 53 men and 22 women with a mean age of 47.8 years (range 18-74 y), underwent retroperitoneal laparoscopy for the treatment of complex renal stones between July 2006 and November 2012 in our hospital.
The retroperitoneal laparoscopic procedures for treatment of complex renal stones were completely successful in 73 cases, while 2 cases converted to open surgery. The operative time was 85-190 min with a mean of 96 min. The estimated blood lost was 20-400 mL with a mean of 80 mL. After the operation 7 patients experienced urinary leakage. Ultrasonography, x-ray of the kidney, ureter and bladder, and intravenous urography were reviewed at post-procedural follow-up at 6-82 months. No hydronephrosis aggravation was found, and there was no calculus recurrence.
The merits of retroperitoneal laparoscopy for the treatment of complex renal stones include sparing the nephron, less bleeding, short hospitalization, quick postoperative recovery, and controllable procedure after training Success depends on the experience of surgeons and judicious selection of cases.
[Show abstract][Hide abstract] ABSTRACT: Although cystitis glandularis (CG) is a common benign urinary bladder epithelial abnormality, it remains unclear whether CG is a premalignant lesion. Cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) overexpression has recently been reported as a potential tumor initiator or promoter. We evaluated and compared COX-2 and Bcl-2 expression in CG, chronic cystitis (CC), and primary vesicle adenocarcinoma (ADC) tissues.
We conducted a retrospective study to investigate COX-2 and Bcl-2 levels in CG and ADC. We obtained tissue samples from 75 patients (including 11 cases of CC, 30 typical cases of CG (CGTP), 30 cases of intestinal CG (CGIT), and 4 cases of ADC) between 1989 and 2009 from the Surgical Pathology Archives of the No. 2 People's Hospital of Zhenjiang, affiliated with Jiangsu University. COX-2 and Bcl-2 immunohistochemical staining was performed on all tissues. Nine normal bladder epithelial specimens were evaluated as control samples. Correlations between COX-2 and Bcl-2 expression in CG were also analyzed.
COX-2 and Bcl-2 expression was higher in the ADC group compared to other groups (p < 0.05). COX-2 and Bcl-2 levels were higher in the CGIT group compared to the CGTP group (p = 0.000 for both). The CGIT and CGTP groups both showed higher COX-2 expression compared to the CC group (p = 0.000 for both). There was no difference in Bcl-2 expression between the CGTP and CC groups (p = 0.452). Additionally, the difference in COX-2 and Bcl-2 expression between the control and CC groups was also insignificant (p = 0.668 and p = 0.097, respectively). Finally, we found that COX-2 and Bcl-2 levels were positively related (r = 0.648, p = 0.000).
COX-2 and Bcl-2 overexpression in the CG group suggests that CG, particularly the intestinal type, may be a premalignant lesion that converts into a tumor in the presence of carcinogens.
[Show abstract][Hide abstract] ABSTRACT: One-carbon metabolism is the basement of nucleotide synthesis and the methylation of DNA linked to cancer risk. Variations in one-carbon metabolism genes are reported to affect the risk of many cancers, including renal cancer, but little knowledge about this mechanism is known in Chinese population.
Each subject donated 5 mL venous blood after signing the agreement. The study was approved by the Institutional Review Board of the Nanjing Medical University, Nanjing, China. 18 SNPs in six one-carbon metabolism-related genes (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) were genotyped in 859 clear cell renal cell carcinoma (ccRCC) patients and 1005 cancer-free controls by the Snapshot.
Strong associations with ccRCC risk were observed for rs706209 (P = 0.006) in CBS and rs9332 (P = 0.027) in MTRR. Compared with those carrying none variant allele, individuals carrying one or more variant alleles in these two genes had a statistically significantly decreased risk of ccRCC [P = 0.001, adjusted odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.06-0.90]. In addition, patients carrying one or more variant alleles were more likely to develop localized stage disease (P = 0.002, adjusted OR = 1.37, 95%CI = 1.11-1.69) and well-differentiated ccRCC (P<0.001, adjusted OR = 1.42, 95%CI = 0.87-1.68). In the subgroup analysis, individuals carrying none variant allele in older group (P = 0.007, adjusted OR = 0.67, 95%CI = 0.49-0.91), male group (P = 0.007, adjusted OR = 0.71, 95%CI = 0.55-0.92), never smoking group (P = 0.002, adjusted OR = 0.68, 95%CI = 0.53-0.88) and never drinking group (P<0.001, adjusted OR = 0.68, 95%CI = 0.53-0.88) had an increased ccRCC risk.
Our results suggest that the polymorphisms of the one-carbon metabolism-related genes are associated with ccRCC risk in Chinese population. Future population-based prospective studies are required to confirm the results.
PLoS ONE 11/2013; 8(11):e81129. DOI:10.1371/journal.pone.0081129 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abnormal expression of Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of apoptosis protein (IAP) family, has implications in many types of cancer and is considered as a new therapeutic target. We suppose that genetic variant rs9904341 in the 5[prime] UTR region of survivin gene may be associated with the development and progression of prostate cancer (PCa) in Chinese population.
TaqMan assay method was used to genotype the polymorphism in the hospital-based case--control analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The genetic associations with the occurrence and progression of PCa were calculated by logistic regression.
Our results indicated that compared with GG genotypes, there was a statistically significant increased risk of PCa associated with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that the association was more pronounced in subgroups of nondrinkers, nonsmokers and those without a family history of cancer (all P < 0.05). In addition, we observed that PSA >= 20 was more frequent in patients carrying GC/CC genotypes than in those with a wild type genotype.
The functional survivin rs9904341 genetic variant may have a substantial influence on the PCa susceptibility and evolution.
BMC Cancer 07/2013; 13(1):356. DOI:10.1186/1471-2407-13-356 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152.
The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR.
TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152.
Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.
The Prostate 07/2013; 73(10). DOI:10.1002/pros.22656 · 3.57 Impact Factor