Zike Qin

Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionTo 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.

Multilayered molecular profiling supported the monoclonal origin of metastatic renal cell carcinoma

Primary renal cell carcinomas (pRCCs) have a high degree of intratumoral heterogeneity and are composed of multiple distinct subclones. However, it remains largely unknown that whether metastatic renal cell carcinomas (mRCCs) also have startling intratumoral heterogeneity or whether development of mRCCs is due to early dissemination or late diagnosis. To decipher the evolution of mRCC, we analyzed the multilayered molecular profiles of pRCC, local invasion of the vena cava (IVC), and distant metastasis to the brain (MB) from the same patient using whole‐genome sequencing, whole‐exome sequencing, DNA methylome profiling, and transcriptome sequencing. We found that mRCC had a lower degree of heterogeneity than pRCC and was likely to result from recent clonal expansion of a rare, advantageous subclone. Consequently, some key pathways that are targeted by clinically available drugs showed distinct expression patterns between pRCC and mRCC. From the genetic distances between different tumor subclones, we estimated that the progeny subclone giving rise to distant metastasis took over half a decade to acquire the full potential of metastasis since the birth of the subclone that evolved into IVC. Our evidence supported that mRCC was monoclonal and distant metastasis occurred late during renal cancer progression. Thus, there was a broad window for early detection of circulating tumor cells and future targeted treatments for patients with mRCCs should rely on the molecular profiles of metastases.

Preoperative Albumin to Globulin Ratio (AGR) as prognostic factor in renal cell carcinoma

Background: Malnutrition and systemic inflammatory response are frequently associated with prognosis in patients with several types of cancer, including renal cell carcinoma (RCC). The study is aimed to investigate the ability of preoperative serum albumin to globulin ratio (AGR) to predict the long-term mortality of RCC patients. Methods: The study is a retrospective study of an unselected cohort of 895 RCC patients who underwent a curative radical or partial nephrectomy at the Department of Urology in the Sun Yat-Sen University Cancer Center between January 2000 and December 2012 and had documented preoperative serum total protein and albumin (ALB) levels. The preoperative AGR was calculated as the ratio of ALB to (total protein-ALB) and its association with other clinical indices was assessed using survival analysis. Results: Low preoperative AGR was associated with older population, lower hemoglobin, higher total protein, lower ALB, lower body mass index and advanced stage. The univariate and multivariate Cox analyses demonstrated that preoperative AGR was an independent prognostic indicator of overall survival (OS) (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.43 to 0.93, P=0.022). In addition, patients with low preoperative AGR at pT1-2, pT3-4, pN0, pN1, pM0 and pM1 stages had significantly shorter OS than patients with high preoperative AGR. Conclusion: Preoperative AGR is a proven objective, reproducible, inexpensive survival predictor of RCC patients following surgical resection and should be considered for routine clinical use.

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

ABSTRACT Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+ TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+ gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.

Preoperative serum cystatin-C as a potential biomarker for prognosis of renal cell carcinoma.

Purpose The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients. Patients and methods The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC. Results Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (P<0.001), pN0 (P<0.001) and pM0 stages (P<0.001). Moreover, Multivariate Cox regression analyses also showed that in the 306 patients without metastasis, high preoperative Cys-C was also associated with shorter disease-free survival (DFS) (HR, 3.50; P = 0.013). Conclusions An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up.

The C-reactive protein/albumin ratio, a validated prognostic score, predicts outcome of surgical renal cell carcinoma patients

BackgroundThe preoperative C-reactive protein/Albumin (CRP/Alb) ratio has been shown to be valuable in predicting the prognosis of patients with certain cancers. The aim of our study is to explore its prognostic value in patients with renal cell carcinoma (RCC).MethodsA retrospective study was performed in 570 RCC patients underwent radical or partial nephrectomy including 541 patients who received full resection of localized (T1-3xa0N0/+ M0) RCC. The optimal cutoff value of CRP/Alb was determined by the receive operating characteristic (ROC) analysis. The impact of the CRP/Alb and other clinicopathological characteristics on overall survival (OS) and disease-free survival (DFS) was evaluated using the univariate and multivariate Cox regression analysis.ResultsThe optimal cutoff of CRP/Alb ratio was set at 0.08 according to the ROC analysis. Multivariate analysis indicated that CRP/Alb ratio was independently associated with OS of RCC patients underwent radical or partial nephrectomy (hazard ratio [HR]: 1.94; 95% confidence interval [95% CI]: 1.12–3.36; Pu2009=u20090.018), and DFS of localized RCC patients underwent full resection (HR: 2.14; 95% CI: 1.22–3.75; Pu2009=u20090.008).ConclusionElevated CRP/Alb ratio was an independent prognostic indicator for poor OS in patients underwent radical or partial nephrectomy and DFS of localized RCC patients underwent full resection. Overall, CRP/Alb may help to identify patients with high relapse risk.

Surveillance for patients with clinical stage I nonseminomatous testicular germ cell tumors

AbstractPurposenTo assess the prognostic value of histological parameters in patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) undergoing active surveillance post-orchiectomy.nMethodsPrognoses 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.Results 23.1xa0% of the 78 investigated patients with CSI NSGCT relapsed, within a median time of 5.6xa0months It was determined using multivariate analysis that lymph vascular invasion (LVI) (OR 6.521; 95xa0% CI 1.872–22.721; pxa0=xa00.003) and the predominant presence of yolk sac tumor (greater than 50xa0%) (OR 3.537; 95xa0% CI 1.076–11.628; pxa0=xa00.038) independently correlated with relapse-free survival (RFS). Patients were categorized accordingly into three risk groups: low risk [<50xa0% presence of yolk sac tumor and LVI (−); nxa0=xa041], intermediate risk [50xa0% or greater presence of yolk sac tumor and LVI (+); nxa0=xa029], and high risk [50xa0% or greater presence of yolk sac tumor and LVI (+); nxa0=xa08]. Relapse rates of the low-risk, intermediate-risk, and high-risk groups were 7.3, 31.0, and 75.0xa0%, respectively.nConclusionsLVI 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.

Modification of N staging systems for penile cancer: a more precise prediction of prognosis

Background:The tumour-node-metastasis (TNM) classification is the most widely used tool for penile cancer. However, the current system is based on few studies and has been unchanged since 2009. We determined whether a modified pathological N staging system that incorporates the laterality and number of lymph node metastases (LNMs) increases the accuracy of the results in predicting survival compared with the 7th edition of the pathological N staging system of the American Joint Committee on Cancer (AJCC) for penile cancer.Methods:The clinical and histopathologic data from 111 patients with penile cancer with LNMs were analysed. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the impact of the clinical and pathological factors on disease-specific survival of these patients. The predictive accuracy was further assessed using the concordance index.Results:According to the 7th edition of the pathological N classification, the 3-year disease-specific survival (DSS) rates for patients with pN1, pN2, and pN3 disease are 89.6%, 65.9%, and 33.6%, respectively (PN1–N2=0.030, PN2–N3<0.001, P<0.001). Under the modified pathological N category criteria, the 3-year DSS rates for pN1, pN2, and pN3 patients were 90.7%, 60.5%, and 31.4%, respectively (PN1–N2=0.005, PN2–N3=0.004, P<0.001). In separate multivariate Cox regression models, only modified N stages (hazard ratio: 4.877, 10.895; P=0.018, P<0.001) exhibited independent effects on the outcome. The accuracy of the modified pathological N category was significantly increased.Conclusions:The modified pathological N staging system is a better reflection of the prognosis of patients with penile cancer. Our study should contribute to the improvement of prognostic stratification and systemic treatment to avoid overtreatment of patients.

Effcacy of radical cystectomy plus adjuvant intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced bladder cancer

Background 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. Methods 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. Results 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. Conclusions 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.

Intra-arterial chemotherapy is reliable in preventing high-risk superficial bladder cancer from recurrence and progression

Abstract The purpose of this prospective study was to evaluate the therapeutic effects of intra-arterial chemotherapy in preventing high-risk superficial bladder cancer from recurrence and progression. From May 2003 to December 2007, 52 patients were divided randomly into 2 groups. Twenty-five patients were given intra-arterial chemotherapy with gemcitabine and cisplatin, and 27 patients received intravesical instillation with epirubicin. After 6-67 months of follow-up (median, 40 months), the overall recurrence-free rates of the intra-arterial chemotherapy and intravesical instillation groups were 83.3% and 33.4%, respectively (p=0.001 log rank). Tumor progression was not found in the intra-arterial chemotherapy group while 7 patients in the intravesical instillation group had tumor progression. The overall tumor progression free rates were 100% and 58.5%, respectively (p=0.009 log rank). The patients with functional bladders were 100% and 81.5% in the intra-arterial chemotherapy and intravesical instillation groups after 67 months of follow-up, respectively. In conclusion, intra-arterial chemotherapy is more effective than intravesical instillation in preventing high-risk superficial bladder cancer from recurrence and progression.