[Show abstract][Hide abstract] ABSTRACT: Background
Muscle invasive bladder cancer (MIBC) is often lethal and non-MIBC (NMIBC) can recur and progress, yet prognostic markers are currently inadequate. SAM68, a member of RNA-binding proteins, has been reported to contribute to progression of other cancers. The aim of this study is to investigate the potential utility of SAM68 in the progression and prognosis of bladder cancer.
Quantitative PCR and immunohistochemistry were utilized to examine the expression of SAM68 in ten pairs of MIBC and adjacent normal bladder urothelium, and eight pairs of MIBC and non-MIBC (NMIBC) tissues from the same patient. Moreover, SAM68 protein expression level and localization were examined by immunohistochemistry in 129 clinicopathologically characterized MIBC samples. Prognostic associations were determined by multivariable analysis incorporating standard prognostic factors.
SAM68 expression was elevated in MIBC tissues compared with adjacent normal bladder urothelium, and was increased at both transcriptional and translational levels in MIBC tissues compared with NMIBC tissues of the same patient. For MIBC, high expression and nucleus-cytoplasm co-expression of SAM68 were associated with higher T-stage, higher N-stage and worse recurrence-free survival. Five-year recurrence-free survival was 80% and 52.9% for MIBC patients with low and high SAM68 expression, respectively (p = 0.001). SAM68 nucleus-cytoplasm co-expression associated with worse 5-year recurrence-free survival rate (49.2%) than SAM68 expression confined to the nucleus (82.5%) or cytoplasm (75.5%) alone. On multivariable analysis SAM68 expression level, SAM68 nucleus-cytoplasm co-expression, T-stage, and N-stage were all independent prognostic factors for recurrence-free survival of MIBC patients.
SAM68 expression is increased in MIBC when compared to normal urothelium and NMIBC, and appears to be a potentially useful prognostic marker for MIBC.
BMC Cancer 05/2015; 15(1). DOI:10.1186/s12885-015-1367-x · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the prognostic value of histological parameters in patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) undergoing active surveillance post-orchiectomy.
Prognoses and recurrence patterns were investigated in 78 patients with CSI NSGCT who underwent orchiectomy. Immediately following orchiectomy, patients participated in active surveillance between 1999 and 2013 at Sun Yat-sen University Cancer Center, Guangzhou, China.
23.1 % of the 78 investigated patients with CSI NSGCT relapsed, within a median time of 5.6 months It was determined using multivariate analysis that lymph vascular invasion (LVI) (OR 6.521; 95 % CI 1.872-22.721; p = 0.003) and the predominant presence of yolk sac tumor (greater than 50 %) (OR 3.537; 95 % CI 1.076-11.628; p = 0.038) independently correlated with relapse-free survival (RFS). Patients were categorized accordingly into three risk groups: low risk [<50 % presence of yolk sac tumor and LVI (-); n = 41], intermediate risk [50 % or greater presence of yolk sac tumor and LVI (+); n = 29], and high risk [50 % or greater presence of yolk sac tumor and LVI (+); n = 8]. Relapse rates of the low-risk, intermediate-risk, and high-risk groups were 7.3, 31.0, and 75.0 %, respectively.
LVI and a predominant presence of yolk sac tumor are crucial risk factors for relapse of CSI NSGCT. For patients without either of these risk factors, active surveillance post-orchiectomy is a safe and effective approach for the initial management of CSI NSGCT.
World Journal of Urology 12/2014; 33(9). DOI:10.1007/s00345-014-1454-7 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bladder cancer is the ninth most common cancer in the world; fewer than 15% of transitional-cell carcinoma patients survive 2 years if left untreated. Although radical cystectomy is the standard treatment of choice, much of them relapse and the necessity of adjuvant chemotherapy is still under debate. The aim of the study was to evaluate the efficacy of adjuvant intraarterial chemotherapy (IAC) with gemcitabine and cisplatin (GC) on locally advanced bladder cancer.
This is a retrospective study on 60 patients with locally advanced bladder carcinoma who underwent radical cystectomy between May 2000 and June 2011. Patients were studied in two groups based on IAC and followed up for up to 5 years.
Among 60 patients, there were 25 patients who underwent IAC (GC) after radical cystectomy (the IAC group) and 35 patients who underwent radical cystectomy alone (the control group). Although not significant, the relapse rates were slightly reduced in the IAC group than in the control group. Patients with IAC had a reduction in mortality compared with patients without IAC over 5 years. Specifically, IAC significantly reduced about 82% of mortality within the first year (hazard ratio = 0.18, 95% CI 0.03-0.97, P = 0.04). Additionally, IAC was well tolerated and safe. The most common adverse effect was transient myelosuppression (10/25, 40%), which was resolved by various medical treatments.
Compared with radical cystectomy alone, radical cystectomy in combination with adjuvant IAC moderately but significantly reduces 1-year mortality. Our preliminary data showed only marginal benefit for the early survival. However, a randomized clinical study is needed to determine the long-term survival benefit.
Chinese medical journal 04/2014; 127(7):1249-54. DOI:10.3760/cma.j.issn.0366-6999.20131612 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression pattern of H3K27me3 and its clinicopathological/prognostic significance in urothelial carcinoma of bladder (UCB) are unclear. In this study, upregulated expression of H3K27me3 protein was observed in the majority of UCBs by Western blotting. High expression of H3K27me3 was examined by IHC in 59/126 (46.8%) of UCB tissues and in 18/72 (25.0%) of normal urothelial bladder epithelial tissues (P = 0.002). High expression of H3K27me3 was associated with multifocal tumors and lymph node metastases (P < 0.05). Patients with high expression of H3K27me3 had shorter cancer-specific survival (CSS) time than patients with low expression of H3K27me3 (P < 0.001). In different subsets of UCB patients, high expression of H3K27me3 was also a prognostic indicator in patients with grade 2 and grade 3, pT1, pT2, pT3, and pN- disease (P < 0.05). Importantly, expression of H3K27me3 was an independent predictor for CSS (P < 0.001) of UCB patients treated with radical cystectomy (RC). Our data suggests that high expression of H3K27me3 is an independent molecular marker for predicting poor prognosis of UCB patients treated with RC.
[Show abstract][Hide abstract] ABSTRACT: Age at diagnosis has been shown to be an independent prognostic factor of localized renal cell carcinoma (RCC) in several studies. We used contemporary statistical methods to reevaluate the effect of age on the cancer-specific survival (CSS) of localized RCC.
1,147 patients with localized RCC who underwent radical nephrectomy between 1993 and 2009 were identified in our four institutions. The association between age and CSS was estimated, and the potential threshold was identified by a univariate Cox model and by martingale residual analysis. Competing risks regression was used to identify the independent impact of age on CSS. The median age was 52 years (range, 19-84 years). The median follow-up was 61 months (range, 6-144 months) for survivors. A steep increasing smoothed martingale residual plot indicated an adverse prognostic effect of age on CSS. The age cut-off of 45 years was most predictive of CSS on univariate Cox analysis and martingale residual analysis (p = 0.005). Age ≤45 years was independently associated with a higher CSS rate in the multivariate Cox regression model (HR = 1.59, 95% CI = 1.05-2.40, p = 0.027) as well as in competing risks regression (HR = 3.60, 95% CI = 1.93-6.71, p = 0.001).
Increasing age was associated with a higher incidence of cancer-specific mortality of localized RCC. Age dichotomized at 45 years would maximize the predictive value of age on CSS, and independently predict the CSS of patients with localized RCC.
PLoS ONE 10/2012; 7(10):e48489. DOI:10.1371/journal.pone.0048489 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Invasive bladder cancer is a lethal disease for which effective prognostic markers as well as potential therapy targets are still lacking. Nkx2.8 (Nk2 homeobox 8), a novel member of the NK-2 gene family, was reported to play an important role in the development and progression of human cancer. Herein, we reported that Nkx2.8 was markedly reduced in bladder cancer tissues compared with matched adjacent normal urothelial tissues. Nkx2.8 levels were inversely correlated with advanced T classification, N classification, tumor multiplicity, high proliferation index (Ki-67) and poor survival of patients. Furthermore, we found that overexpression of Nkx2.8 in bladder cancer cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing Nkx2.8 dramatically enhanced cell proliferation. Moreover, we demonstrated that overexpression of Nkx2.8 resulted in G(1)/S phase arrest, accompanied by upregulation of p27(Kip1), downregulation of cyclin D1 and p-FOXO3a and inhibition of MEK/ERK pathway activity. Meanwhile, silencing Nkx2.8 led to acceleration of G(1)/S transition, downregulation of p27(Kip1), upregulation of cyclin D1 and p-FOXO3a and increase of MEK/ERK pathway activity. These findings suggest that Nkx2.8 plays a potential tumor suppressor role in bladder cancer progression and represents a valuable clinical prognostic marker of this disease.
[Show abstract][Hide abstract] ABSTRACT: The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs.
The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC.
The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients.
To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC.
BMC Cancer 09/2011; 11(1):413. DOI:10.1186/1471-2407-11-413 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective study aimed to examine the expression and localization of SAM68 (Src-associated in mitosis, 68 kDa) in a larger cohort of surgical specimens of renal cell carcinoma and their correlation with the progression of human renal cell carcinoma.
The protein and mRNA expression levels of SAM68 in normal renal tubular epithelial cells, renal cell carcinoma cell lines, as well as nine pairs of renal cell carcinoma and matched tumor-adjacent renal tissues were examined using reverse transcription-PCR and Western blot. Moreover, SAM68 protein expression and localization in 241 clinicopathologically characterized renal cell carcinoma samples were examined by immunohistochemistry. Prognostic and diagnostic associations were examined by statistical analyses.
SAM68 was markedly overexpressed in renal cell carcinoma cell lines and renal cell carcinoma tissues at both the transcriptional and translational levels. Immunohistochemical analysis revealed high SAM68 protein expression in 129 of the 241 (53.5%) paraffin-embedded archival renal cell carcinoma specimens. Moreover, there was a significant correlation between SAM68 expression and pathologic stage (P < 0.001), T classification (P = 0.003), N classification (P = 0.001), M classification (P = 0.006), and Fuhrman grade (P < 0.001). Patients with higher SAM68 expression had shorter overall survival time than patients with lower SAM68 expression, and the cytoplasmic localization of SAM68 significantly correlated with clinicopathologic grade and outcome. Multivariate analysis indicated that SAM68 protein overexpression and cytoplasmic localization were independent predictors for poor survival of renal cell carcinoma patients.
Our results suggest that SAM68 could represent a novel and useful prognostic marker for renal cell carcinoma. High SAM68 expression and cytoplasmic localization are associated with poor overall survival in renal cell carcinoma patients.