Yuanfeng Yang

P2X7 receptor predicts postoperative cancer‐specific survival of patients with clear‐cell renal cell carcinoma

The P2X7 receptor, an ATP‐gated plasma membrane ion channel, is involved in inflammation, apoptosis and cell proliferation, and thereby plays a crucial role during oncogenic transformation in various malignancies. This study aims to evaluate the impact of P2X7 receptor expression on postoperative cancer‐specific survival of patients with clear‐cell renal cell carcinoma (ccRCC). A total of 273 patients with ccRCC undergoing nephrectomy at a single institution were retrospectively enrolled in this study, among which 86 patients died of this disease and six patients died of other causes. Clinicopathologic features and cancer‐specific survival (CSS) were recorded. P2X7 expression was assessed by immunohistochemistry in clinical specimens. Kaplan–Meier method with log rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on CSS. Concordance index was calculated to assess prognostic accuracy of prognostic models. Median follow‐up period was 90 months (range, 11–120 months). Intratumoral P2X7 expression was significantly lower than peritumoral tissues (P < 0.001). Moreover, high intratumoral P2X7 expression, which was significantly associated with shorten CSS (P < 0.001), high TNM stage (P = 0.038), Fuhrman grade (P = 0.035), SSIGN (stage, size, grade, and necrosis) score (P = 0.021) and University of California Integrated Staging System (UISS) score (P = 0.007), was indicated to be an independent prognostic factor for CSS (hazard ratio [HR], 1.693; P = 0.034). The prognostic accuracy of TNM stage, UISS and SSIGN scoring models was improved when intratumoral P2X7 expression was added. Intratumoral P2X7 expression is a potential independent adverse prognostic indicator for postoperative CSS of patients with ccRCC.

Prognostic value of preoperative lymphocyte to monocyte ratio in patients with nonmetastatic clear cell renal cell carcinoma

Growing evidence indicates that systemic inflammation involves in cancer development and progression. Preoperative lymphocyte to monocyte ratio (LMR) has been estimated as an independent prognostic factor of various cancers. We investigated the prognostic value of LMR in nonmetastatic clear cell renal cell carcinoma (ccRCC) patients after surgery. We retrospectively recruited 430 consecutive patients with nonmetastatic ccRCC (T1-3N0M0) who underwent curative nephrectomy between 2008 and 2009 at a single center in China. Lymphocyte and monocyte counts were obtained at hospitalization before surgery. Preoperative LMR as a continuous variable and as a dichotomized variable at a level of 3.25, which was the 25th percentile value, were analyzed in unvariable and multivariable Cox regression models, respectively. Concordance index (C-index) was calculated to assess predictive accuracy. Kaplan-Meier method was applied to compare survival curves. As both of the continuous and dichotomized variable, decreased preoperative LMR was proven to be independent prognostic factors of recurrence-free survival (P = 0.039 and P = 0.003, respectively) and overall survival (P = 0.002 and P < 0.001, respectively). Further examination revealed that the dichotomized LMR could enhance the predictive accuracy of each of the existing prognostic models among intermediate-risk to high-risk patients. The preoperative LMR is an independent prognostic factor of recurrence-free survival and overall survival for nonmetastatic ccRCC patients after surgery, and it can be used in tandem with established prognostic systems to further enhance outcome prediction in intermediate-risk to high-risk patients.

High APOBEC3B expression is a predictor of recurrence in patients with low-risk clear cell renal cell carcinoma

PURPOSE APOBEC3B is a member of the cytosine deaminase family, which converts cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction. Recent evidence has revealed that APOBEC3B-catalyzed genomic DNA deamination could provide genetic fuel for cancer development, metastasis, and even treatment resistance. The aim of this study was to assess the association between APOBEC3B expression and the risk of recurrence after surgery in patients with renal cell carcinoma (RCC). METHODS We retrospectively enrolled 299 consecutive patients with RCC who underwent nephrectomy at a single center in 2008. Clinicopathologic variables and recurrence-free survival (RFS) were recorded. APOBEC3B expression levels were determined by immunohistochemistry in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on RFS. The Harrell concordance index was calculated to assess predictive accuracy. RESULTS High APOBEC3B expression was associated with an increased risk of recurrence in patients with clear cell RCC (ccRCC) (P<0.001) rather than in patients with non-ccRCC (P = 0.247). After backward elimination, APOBEC3B expression was identified as an independent prognostic factor for RFS in patients with clear cell histology (P = 0.016). The predictive accuracy of the Leibovich prognostic score was improved when APOBEC3B expression was incorporated. Notably, the improvement in prediction mainly took place in patients with low-risk disease defined by the Leibovich score. CONCLUSIONS High APOBEC3B expression is an independent predictor of recurrence in patients with ccRCC, and the prognostic value is most prominent in those with low-risk disease.

CXC chemokine receptor 2 is associated with postoperative recurrence and survival of patients with non-metastatic clear-cell renal cell carcinoma

BACKGROUND Aberrant CXC chemokine receptor 2 (CXCR2) expression has been shown to promote angiogenesis and proliferation in renal cell carcinoma (RCC). Our current study aims to evaluate the prognostic significance of CXCR2 in patients with non-metastatic clear-cell renal cell carcinoma (ccRCC). METHODS We retrospectively enrolled 375 patients with non-metastatic ccRCC undergoing nephrectomy at Zhongshan Hospital, Fudan University between 2003 and 2008. The cohort was split into a training set (n=184) and a validation set (n=191). CXCR2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated. RESULTS CXCR2 expression was significantly associated with tumour size (P=0.036 and P=0.016, respectively) and Fuhrman grade (P=0.009 and P=0.001, respectively) in the training and validation sets. Moreover, high CXCR2 expression indicated poor overall survival (OS) (P<0.001 and P=0.001, respectively) and recurrence-free survival (P<0.001 and P<0.001, respectively) in the training and validation sets. The incorporation of CXCR2 into the T stage and Fuhrman grade would help to refine individual risk stratification. Furthermore, CXCR2 expression was identified as an independent adverse prognostic factor for survival (P<0.001) and recurrence (P<0.001). A predictive nomogram was generated with identified independent prognosticators to assess patient recurrence-free survival at 5 and 10 years. CONCLUSIONS CXCR2 is a potential independent adverse prognostic biomarker for recurrence and survival of patients with non-metastatic ccRCC after nephrectomy.

Beta-1,4-galactosyltransferase II predicts poor prognosis of patients with non-metastatic clear-cell renal cell carcinoma

Beta-1,4-galactosyltransferase II is found to be associated with the alterations of tumor-related glycosylation. However, the clinical significance of beta-1,4-galactosyltransferase II in non-metastatic clear-cell renal cell carcinoma has not been reported up to now. Herein, our researches suggested that the expression level of beta-1,4-galactosyltransferase II was first found to be positively associated with tumor size, Fuhrman grade, lymphovascular invasion, rhabdoid differentiation, tumor necrosis and poor overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma, both in training set and validation set. Moreover, beta-1,4-galactosyltransferase II expression was identified as an independent adverse prognosticator for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Ultimately, prognostic accuracy of the nomogram integrating beta-1,4-galactosyltransferase II with other independent prognostic parameters was dramatically improved for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Taken together, beta-1,4-galactosyltransferase II is a potential independent adverse prognostic factor for postoperative recurrence and survival, which could be developed as a useful biomarker for non-metastatic clear-cell renal cell carcinoma by a series of further independent and retrospective studies, so as to help the postsurgical management of clear-cell renal cell carcinoma patients.

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma.

AbstractMucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC.The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram.In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy.MUC4 expression is an independent prognostic factor for OS in patients with ccRCC.

The Presence of Vascular Mimicry Predicts High Risk of Clear Cell Renal Cell Carcinoma after Radical Nephrectomy

PURPOSE Vascular mimicry is a type of tumor cell plasticity. The aim of this study was to determine the prognostic value of vascular mimicry in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS We performed a retrospective cohort study in 387 patients with clear cell renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University between 2008 and 2009. Pathological features, baseline patient characteristics and followup data were recorded. Vascular mimicry in clear cell renal cell carcinoma tissue was identified by CD31-periodic acid-Schiff double staining. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival. The concordance index and the Akaike information criterion were used to assess the predictive accuracy and sufficiency of different models. RESULTS Positive vascular mimicry staining occurred in 25 of 387 clear cell renal cell carcinoma cases (6.5%) and it was associated with an increased risk of recurrence (log-rank p <0.001). Incorporating vascular mimicry into pT stage, Fuhrman grade and Leibovich score helped refine individual risk stratification. Moreover, vascular mimicry was identified as an independent prognostic factor (p = 0.001). It was entered into a nomogram together with pT stage, Fuhrman grade, tumor size and necrosis. In the primary cohort the Harrell concordance index for the established nomogram to predict recurrence-free survival was slightly higher than that of the Leibovich model (0.850 vs. 0.823), which failed to reach statistical significance (p = 0.158). CONCLUSIONS Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with clear cell renal cell carcinoma after radical nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for clear cell renal cell carcinoma.

High expression of Mucin13 associates with grimmer postoperative prognosis of patients with non-metastatic clear-cell renal cell carcinoma

Background Mucin13 (MUC13) is a transmembrane glycoprotein that is aberrantly expressed in ovarian and gastro-intestinal tumors, but its role in renal cell carcinoma remains elusive. The purpose of this study is to evaluate the prognostic value of MUC13 expression in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) after surgical resection. Results MUC13 high expression was associated with high Fuhrman grade (p < 0.001), high SSIGN score (p = 0.011), early recurrence (p < 0.001) and poor survival (p < 0.001). Multivariate Cox regression analysis identified MUC13 expression as an independent prognostic factor for RFS and OS of ccRCC patients. A nomogram integrating MUC13 expression and other independent prognosticators was established to predict RFS and OS of ccRCC patients. Optimal agreement was shown between the predictions and observations in calibration curves. Matrials and methods This study enrolled 410 postoperative non-metastatic ccRCC patients at a single institution. Clinicopathologic variables, recurrence-free survival (RFS), and overall survival (OS) were recorded. MUC13 expression was detected by immunohistochemical staining in tumor specimens. Association of MUC13 expression with clinicopathological factors was explored. Kaplan-Meier analysis was performed to compare survival curves. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on RFS and OS. A prognostic nomogram was constructed based on the independent prognostic factors identified by multivariate analysis. Conclusions MUC13 high expression is a novel independent adverse prognostic factor of clinical outcome in non-metastatic ccRCC patients after surgery.

Granulocyte macrophage colony-stimulating factor predicts postoperative recurrence of clear-cell renal cell carcinoma.

Background Granulocyte macrophage colony-stimulating factor (GM-CSF) is currently widely used as an adjuvant in cancer immunotherapy. However, recent studies have shown that GM-CSF can impair anti-tumor immune responses. Thus the role of GM-CSF in clear-cell renal cell carcinoma (ccRCC) remains unraveled. Our present study aims to investigate the prognostic significance of intratumoral GM-CSF in patients with clinically localized ccRCC. Results A high intratumoral GM-CSF expression was significantly associated with lymph node metastases (P = 0.009), high TNM stage (P = 0.031), high Fuhrman grade (P < 0.001), presence of tumor necrosis (P = 0.005), and high Leibovich scores (P < 0.001). In addition, the prognostic significance of intratumoral GM-CSF expression was restricted to patients with Leibovich intermediate/high-risk (P = 0.001). Furthermore, a high intratumoral GM-CSF expression was demonstrated as an independent prognostic factor of reduced RFS (P = 0.018). Incorporation of the intratumoral GM-CSF expression into a prognostic model including TNM stage, Fuhrman grade, tumor necrosis and lymphovascular invasion generated a nomogram, which predicted accurately 3- and 5-year survival for ccRCC patients. Materials and Methods This study comprised 233 clinically localized (T1-3N0-1M0) ccRCC patients undergoing nephrectomy in 2008 at a single centre. Intratumoral GM-CSF expression was assessed by immunohistochemical staining and its associations with clinicopathologic features and recurrence-free survival (RFS) were evaluated. Conclusions The intratumoral GM-CSF expression, as a potentially independent prognostic biomarker for recurrence, might improve conventional clinical and pathologic analysis to refine outcome prediction for clinically localized ccRCC patients after surgery.

High expression of FUT3 is linked to poor prognosis in clear cell renal cell carcinoma

Background and Purpose Some of the fucosylation catalyzed by fucosyltransferase-III mediates the epithelial-mesenchymal transition and enhances tumor cell-macrophage signaling, which promotes malignant transforming and immune evasion. The aim of the study was to investigate the association between the expression of fucosyltransferase-III and clinical outcomes of patients with clear-cell renal cell carcinoma after surgery. Results High fucosyltransferase-III expression was associated with a greater risk of recurrence (p = 0.002) and shortened overall survival (p < 0.001). We then established a prognostic nomogram including tumor size, pathologic T, N, M stage, coagulative necrosis, lymphovascular invasion and fucosyltransferase-III expression. Furthermore, the predictive accuracy of the Leibovich prognostic score was improved when fucosyltransferase-III expression was added (p = 0.009 for overall survival and p = 0.002 for recurrence-free survival). Materials and Methods We conducted a retrospective cohort study of 406 patients who underwent partial or radical nephrectomy between January 2008 and December 2009 in a single institute. Fucosyltransferase-III expression levels were evaluated by immunohistochemical staining in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on recurrence-free and overall survival. Harrell’s concordance index and Akaike’s Information Criteria were calculated to assess predictive accuracy. Conclusions Fucosyltransferase-III is a predictive factor for poor overall survival and recurrence free survival in patients with ccRCC. The inhibitor of fucosyltransferase-III might be a potential therapeutic method for the disease.BACKGROUND AND PURPOSE Some of the fucosylation catalyzed by fucosyltransferase-III mediates the epithelial-mesenchymal transition and enhances tumor cell-macrophage signaling, which promotes malignant transforming and immune evasion. The aim of the study was to investigate the association between the expression of fucosyltransferase-III and clinical outcomes of patients with clear-cell renal cell carcinoma after surgery. RESULTS High fucosyltransferase-III expression was associated with a greater risk of recurrence (p = 0.002) and shortened overall survival (p < 0.001). We then established a prognostic nomogram including tumor size, pathologic T, N, M stage, coagulative necrosis, lymphovascular invasion and fucosyltransferase-III expression. Furthermore, the predictive accuracy of the Leibovich prognostic score was improved when fucosyltransferase-III expression was added (p = 0.009 for overall survival and p = 0.002 for recurrence-free survival). MATERIALS AND METHODS We conducted a retrospective cohort study of 406 patients who underwent partial or radical nephrectomy between January 2008 and December 2009 in a single institute. Fucosyltransferase-III expression levels were evaluated by immunohistochemical staining in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on recurrence-free and overall survival. Harrells concordance index and Akaikes Information Criteria were calculated to assess predictive accuracy. CONCLUSIONS Fucosyltransferase-III is a predictive factor for poor overall survival and recurrence free survival in patients with ccRCC. The inhibitor of fucosyltransferase-III might be a potential therapeutic method for the disease.