Lijiang Sun

Nutritional screening is strongly associated with overall survival in patients treated with targeted agents for metastatic renal cell carcinoma

Although commonly observed, malnutrition is poorly characterized and frequently underdiagnosed in patients with metastatic renal cell carcinoma (RCC). The ability of nutritional screening tools to predict overall survival (OS) in patients with RCC has not been adequately validated. The objective of this study was to investigate the performance of nutritional screening tools and their additional prognostic value in patients with metastatic RCC treated with targeted therapies.

Prognostic significance of the epithelial-to- mesenchymal transition markers e-cadherin, vimentin and twist in bladder cancer

OBJECTIVE The goal of this study was to utilize long-term patient follow-up to determine whether epithelial-to-mesenchymal transition (EMT)-related markers can predict bladder cancer patient survival and progression of disease. MATERIALS AND METHODS This study included 121 patients with bladder cancer. Sixty-four of these patients presented with non-muscle invasive (NMI, stage T1) bladder cancer and 57 with muscle invasive (MI, stage T2, T3). The patients were diagnosed and treated between May 1998 and July 2012. The EMT markers E-cadherin, Twist, and Vimentin were detected via immunohistochemistry. Univariate and multivariate/Cox analyses were then utilized to determine whether these EMT markers could be useful prognostic markers for predicting bladder cancer patient outcomes. RESULTS Analysis of the 121 bladder cancer patients in this study revealed that the frequency of E-cadherin expression was 59.5% (72/121), Twist was 54.5% (66/121), and Vimentin was 24.8% (30/121). Twist and Vimentin were found to have statistically significant correlations with grade, recurrence, and progression but not with stage, whereas E-cadherin was associated with stage but not with the other parameters. In the univariate analysis, grade (p = 0.02) was the only significant predictor for progression-free survival (PFS). Stage, grade, and expression of E-cadherin, Vimentin and Twist were included in the multivariate analysis of predicting PFS. In this analysis, grade (p = 0.01) and Vimentin expression (p = 0.001) were found to be significant prognostic factors in predicting PFS. CONCLUSIONS Grade and Vimentin are potential independent indicators in predicting bladder cancer progression and survival.

Comparison of preoperative neutrophil–lymphocyte, lymphocyte–monocyte, and platelet–lymphocyte ratios in patients with upper urinary tract urothelial carcinoma undergoing radical nephroureterectomy

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

ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.

Clinical outcome of advanced and metastatic renal cell carcinoma treated with targeted therapy: is there a difference between young and old patients?

Background To assess whether the clinical outcome of advanced and metastatic renal cell carcinoma (mRCC) treated with targeted therapy differs between young and old patients. Patients and methods A total of 327 patients with advanced renal cell carcinoma and mRCC who received targeted therapy in two Chinese clinical centers were analyzed retrospectively. The patients were stratified into three groups: young (aged <45 years), middle-aged (aged 45–64 years), and old (aged ≥65 years). Overall survival (OS) and progression-free survival (PFS) curves were drawn using the Kaplan–Meier method, and Cox’s proportional hazard regression model was used to compare OS and PFS within age groups. Results There were no significant differences among young, middle-aged, and old groups in terms of OS (P=0.087), whereas PFS in the old group was significantly better than in the young and middle-aged groups (P=0.043). Both OS and PFS in the younger groups (aged <65 years) were significantly worse than in the old group (age ≥65 years; median OS, 28.1 vs 28.7 months [P=0.029]; median PFS, 11.4 vs 14 months [P=0.015]). No difference in OS or PFS was found between the young and middle-aged groups. After adjusting for sex, body mass index, smoking status, hypertension, diabetes mellitus, Eastern Cooperative Oncology Group score, history of cytokines, and Fuhrman grade, old age was an independent favorable prognostic factor for OS and PFS compared with younger age (<65 years) (OS, hazard ratio, 0.552 [95% confidence interval, 0.329–0.828; P=0.006]; PFS, hazard ratio, 0.584 [95% confidence interval, 0.401–0.850; P=0.005]). Conclusion Younger patients with advanced renal cell carcinoma and mRCC receiving targeted therapy have a poorer prognosis compared with old patients. These results remain to be examined in prospective cohorts.

Bacillus Calmette–Guérin and anti-PD-L1 combination therapy boosts immune response against bladder cancer

Background Programmed death-ligand 1 (PD-L1) is a critical immune checkpoint molecule which promotes immunosuppression by binding to PD-1 on T-cells in tumor immunity. We have previously identified that activation of toll like receptor 4 (TLR-4), which serves an important role in the induction of antitumor immune response during Bacillus Calmette–Guérin (BCG) immunotherapy, could upregulate PD-L1 expression in bladder cancer (BCa) cells through the classical mitogen-activated protein kinase (MAPK) pathway and subsequently weaken the cytotoxicity of cytotoxic T lymphocyte (CTL). It is, therefore, necessary to investigate the possible potential relationship between PD-L1 expression and BCG immunotherapy. Materials and methods In this study we investigated the effects of BCG treatment on PD-L1 expression in BCa cells and also evaluated the efficacy of BCG and anti-PD-L1 combination therapy in immunocompetent orthotopic rat BCa models. Results We found that PD-L1 expression was obviously upregulated in BCa cells in response to BCG treatment both in vitro and in vivo. Moreover, BCG and anti-PD-L1 combination treatment activated a potent antitumor immune response with the increase in the number and activity of tumor-infiltrating CD8+ T cells, as well as the reduction in myeloid-derived suppressor cells (MDSCs), and eventually elicits prominent tumor growth inhibition and prolonged survival, and was found to be much more effective than either agent alone. Conclusion These findings highlight the adaptive dynamic regulation of PD-L1 in response to BCG immunotherapy and suggest that combination of BCG immunotherapy with PD-L1 blockade may be an effective antitumor strategy for improving treatment outcomes of BCa.

Estrogen affects cell growth and IGF-1 receptor expression in renal cell carcinoma

Purpose Both obesity and gender are important etiological factors in renal cell carcinoma (RCC) development, suggesting a pivotal role of sex hormone signaling pathway and insulin-like growth factor (IGF) family in RCC carcinogenesis. Here, we aimed to investigate the effect of estrogen on RCC growth and the possible interaction between estrogen/estrogen receptor (ER) signaling pathway and the IGF axis. Methods ER-α and ER-β were detected in four human RCC cell lines. Cells were treated with 17β-estradiol (E2), and cell proliferation was determined using the cell counting kit-8 assay. Using siRNA, ER-β was downregulated in RCC cells and the effect of E2 on cell growth and IGF-1 receptor (IGF-1R) expression was examined. Results E2 inhibited 786-O cell but not A498 cell growth significantly. After the downregulation of ER-β, E2 showed no obvious inhibitory role in 786-O cells. E2 stimulation increased the expression of IGF-1R in 786-O cells. Downregulation of ER-β, as well as fulvestrant, attenuated the stimulatory effect of E2 on IGF-1R expression. Conclusion Our results revealed that estrogen induced RCC growth inhibition via an ER-β-dependent pathway. Estrogen also upregulated the expression of IGF-1R, suggesting a link between estrogen/ER and IGF axis.

MCT1 regulates aggressive and metabolic phenotypes in bladder cancer

Background: Monocarboxylate transporter isoform 1 (MCT1) is an important molecule in mediating lactate transportation. Recent studies have shown an oncogenic role of MCT1 in cancer development. Methods: In this study, we aimed to investigate the expression and role of MCT1 in bladder cancer (BCa). MCT1 expression was detected in 124 BCa tissues and their clinicopathological significance was analyzed. We also used The Cancer Genome Atlas database to explore the prognostic association of MCT1 with BCa. Cell proliferation, migration and invasion assays were performed on BCa cells in which MCT1 was downregulated. The effect of MCT1 on BCa cell aerobic glycolysis, as well as its association with HIF-1α, was tested. Results: We found that high MCT1 expression correlated with lymph node and distant metastasis. Patients with high-MCT1 expression showed shorter overall survival than those with low-MCT1 expression. Knockdown of MCT1 inhibited BCa cell proliferation, migration and invasion, and affected expression of epithelial-mesenchymal transition related proteins. Downregulation of MCT1 decreased lactate levels in cell medium, as well as HK2, GLUT1 and LDHB expression. In addition, MCT1 expression was partly dependent on HIF-1α. Conclusions: Taken together, our study has shown a prognostic role of MCT1 in BCa, and provided potential diagnostic and therapeutic options for BCa patients.

Impact of Estrogen on the Relationship Between Obesity and Renal Cell Carcinoma Risk in Women

The relationship between obesity and renal cell carcinoma (RCC) has been widely investigated. However, the effect of estrogen on this relationship in female RCC patients has not been evaluated. We conducted a case-control study to investigate the role of estrogen as a potential modifier of the association between obesity and RCC risk in Chinese women. A total of 497 consecutive female patients with pathologically confirmed RCC, including 364 clear cell RCC (ccRCC), were enrolled. Age-matched controls were selected from cancer-free females seeking physical examination in our institution. Estrogen receptor-β (ER-β) and insulin-like growth factor (IGF)-1 receptor (IGF-1R) expression levels were detected in RCC tissues. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression models. We observed a positive association between overweight and RCC risk in pre-menopausal but not post-menopausal women. Similar association was also observed between overweight and ccRCC risk. Overweight pre-menopausal women had an increased risk of RCC (OR: 1.67, 95%CI: 1.01–2.76), as well as an increased risk of ccRCC (OR: 1.73, 95%CI: 1.02–2.99), after adjusting for potential confounders. IGF-1R expression levels were higher in pre-menopausal compared with post-menopausal cases (P = 0.015). These results suggest that estrogen plays an important role in RCC etiology and may modify the association between obesity and RCC risk in women. We hypothesize that estrogen may up-regulate IGF-1R and potentiate the deleterious effects of obesity-related elevations of insulin and IGFs.

Association of ABO Blood Types and Clinicopathological Features of Prostate Cancer

Purpose To investigate the association between ABO blood types and clinicopathological characteristics in patients with prostate cancer (PC). Methods A total of 237 pathologically diagnosed PC patients were enrolled. All patients were classified as low–middle or high-risk group. The correlation of ABO blood types with high-risk PC was determined by univariate and multivariate regression analysis. Results Data indicated 144 (85.7%) patients were stratified as high risk in the non-O group, while 50 (72.5%) patients in the O group (p = 0.025). However, there was no significant difference regarding PSA, Gleason score, stage, or metastasis between O and non-O group (p > 0.05). Univariate logistic regression analyses revealed PSA, Gleason score, and blood type non-O were all correlated with high-risk PC (OR = 1.139, p < 0.001; OR = 9.465, p < 0.001; OR = 2.280, p = 0.018, resp.). In the stepwise multivariate regression analysis, the association between blood type non-O and high-risk PC remained significant (OR = 33.066, 95% CI 2.391–457.323, and p = 0.009) after adjusting for confounding factors as well as PSA and Gleason score. Conclusion The present study firstly demonstrated that non-O blood type was at higher risk of aggressive PC compared with O type, suggesting that PC patients with non-O blood type should receive more attention in clinical practice.