Le Xu

Ruijin Hospital North, Shanghai, Shanghai Shi, China

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Publications (36)122.66 Total impact

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    ABSTRACT: Chemokine (C-C motif) receptor 8 (CCR8) could drive cancer progress through recruiting certain immune cells. Recent evidences revealed the chemotaxis of CCR8+ human malignant tumor cells towards lymph node, and a significantly increased CCR8 expression in renal carcinomas patients. To assess the clinical association between CCR8 expression and the risk of post-surgery recurrence in patients with clear-cell renal cell carcinoma (ccRCC), we detected intratumoral CCR8 expression in 472 post-nephrectomy ccRCC patients retrospectively enrolled. Positive CCR8 staining tumor cell occurred in 26.1% (123 of 472) non-metastatic ccRCC cases, and the positive expression was associated with increased risks of recurrence (Log-Rank P < 0.001). In multivariate analyses, CCR8 expression was identified as an independent prognostic factor (P = 0.008) and entered into a newly-built nomogram together with T stage, Fuhrman grade, tumor size, necrosis and lymphovascular invasion. Calibration curves showed optimal agreement between predictions and observations, while its C-index was higher than that of Leibovich score for predicting recurrence-free survival (RFS) of localised RCC patients (0.854 vs 0.836, respectively; P = 0.044). The practical prognostic nomogram model may help clinicians in decision making and design of clinical studies.
    Preview · Article · Dec 2015 · Oncotarget
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    ABSTRACT: Purpose: Chemokine (C-C motif) ligand 2 (CCL2) is known to recruit monocytes and macrophages to sites of inflammation. Recent studies suggest CCL2 is overexpressed in multiple cancer types and may play a role in the tumor progression. The aim of this study was to assess the association between CCL2 expression and the risk of recurrence after surgery in patients with clear-cell renal cell carcinoma (ccRCC). Methods: This study included 268 ccRCC patients who underwent nephrectomy at a single institute between 2001 and 2004. Clinicopathologic variables and recurrence-free survival (RFS) were recorded. CCL2 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 survival (RFS). Harrell's concordance index was calculated to assess predictive accuracy. Results: High CCL2 expression was associated with a greater risk of recurrence in ccRCC patients (P<0.001). Multivariate analysis confirmed that CCL2 expression was an independent prognostic factor for RFS (P = 0.045). The predictive accuracy of the Leibovich prognostic score was improved when CCL2 expression was added (0.76 vs. 0.71, P<0.001). Notably, the improvement in prediction was more pronounced in patients with low-risk disease. A nomogram integrating CCL2 expression and pathologic factors was then constructed, which predicted 5- and 10-year RFS well for ccRCC patients. Conclusions: High chemokine CCL2 expression is an independent predictor of recurrence in ccRCC patients. Evaluation of CCL2 could help guide postsurgical management for ccRCC patients.
    No preview · Article · Dec 2015 · Urologic Oncology
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    ABSTRACT: This study aims to evaluate the impact of colony stimulating factor-1 (CSF-1) expression on recurrence and survival of patients with clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 267 patients (195 in the training cohort and 72 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, cancer-specific survival (CSS) and recurrence-free survival (RFS) were recorded. CSF-1 levels were assessed by immunohistochemistry in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on CSS and RFS. Concordance index (C-index) was calculated to assess predictive accuracy. In both cohorts, CSF-1 expression positively correlated with advanced Fuhrman grade and necrosis. High CSF-1 expression indicated poor survival and early recurrence of ccRCC patients after surgery, especially those with advanced TNM stage disease. Multivariate Cox regression analysis showed CSF-1 expression was an independent unfavorable prognostic factor for recurrence and survival. The predictive accuracy of the University of California Los Angeles Integrated Staging System (UISS) was significantly improved when CSF-1 expression was incorporated. High CSF-1 expression is a potential adverse prognostic biomarker for recurrence and survival of ccRCC patients after nephrectomy.
    Full-text · Article · Dec 2015 · BMC Cancer
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    ABSTRACT: Solute Carrier Family 1, member 5 (SLC1A5), also named as ASCT2, a major glutamine transporter, is highly expressed in various malignancies and plays a critical role in the transformation, growth and survival of cancer cells. The aim of this study was to assess the clinical significance of SLC1A5 in patients with clear-cell renal cell carcinoma (ccRCC). SLC1A5 expression was evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier method was conducted to compare survival curves. Univariate and multivariate Cox regression models were applied to assess the impact of prognostic factors on overall survival (OS). A nomogram was then constructed on the basis of the independent prognosticators identified on multivariate analysis. The predictive ability of the models was compared using Receiver operating characteristic (ROC) analysis. Our data indicated that high expression of SLC1A5 was significantly associated with advanced TNM stage, higher Fuhrman grade and shorter OS in ccRCC patients. Multivariate analysis confirmed that SLC1A5 was an independent prognosticator for OS. A nomogram integrating SLC1A5 and other independent prognosticators was constructed, which showed a better prognostic value for OS than TNM staging system. In conclusion, high SLC1A5 expression is an independent predictor of adverse clinical outcome in ccRCC patients after surgery.
    Preview · Article · Nov 2015 · Scientific Reports
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    ABSTRACT: Background: Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time. Methods: We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models. Results: The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years. Conclusions: Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.British Journal of Cancer advance online publication, 10 November 2015; doi:10.1038/bjc.2015.379 www.bjcancer.com.
    No preview · Article · Nov 2015 · British Journal of Cancer
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    ABSTRACT: DNA sequencing revealed that mutations in SETD2 occur in 3% to 12% of clear-cell renal cell carcinoma (ccRCC) cases and are associated with poor clinical outcome. In this study, we used an immunohistochemistry (IHC) assay to evaluate the impact of SETD2 loss, with expression of H3K36me3, a nonredundantly histone modification by SETD2, on recurrence and survival of nonmetastatic ccRCC patients after nephrectomy. SETD2 and H3K36me3 were assessed in 192 nonmetastatic ccRCC patients enrolled retrospectively from a single institution. Kaplan–Meier and Cox regression analysis were used to associate prespecified SETD2/H3K36me3 score with overall survival (OS) and recurrence-free survival (RFS). And a nomogram was constructed to predict OS at 10 years. Patients with low expression of SETD2 were prone to possess large tumor size and advanced pT stage. And low H3K36me3 expression was associated with larger tumor size. A prespecified combined score based on SETD2 and H3K36me3 expression remained an independent prognosticator for OS and RFS, which was associated with tumor size, pT stage, and sarcomatoid. Furthermore, using prespecified SETD2/H3K36me3 score could stratify nonmetastatic ccRCC patients into different risk subgroups, especially in patients dichotomized by pT stage and Fuhrman grade, respectively. Finally, the C-index for predicting OS increased from 0.727 to 0.747, after adding SETD2/H3K36me3 score to pT stage and Fuhrman grade. The combined score based on expression of SETD2 and H3K36me3 using IHC could predict poor clinical outcomes in nonmetastatic ccRCC patients, and it may benefit preoperative risk stratification and guide treatment planning in the future.
    No preview · Article · Nov 2015 · Medicine
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    ABSTRACT: 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.
    No preview · Article · Oct 2015 · Tumor Biology
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    ABSTRACT: Background: Colony-stimulating factor 1 receptor (CSF-1R), a single-pass type III transmembrane tyrosine-protein kinase, is mainly involved in inflammation and immune regulation to facilitate the progression of solid tumors. This study aimed to evaluate the impact of CSF-1R expression on clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) after surgery. Methods: We retrospectively enrolled 268 patients with ccRCC undergoing nephrectomy between 2001 and 2004. Clinicopathologic features and cancer-specific survival (CSS) were collected. Western blot analysis was performed in the pairwise comparisons of CSF-1R expression in peritumor and tumor tissues of patients with ccRCC. Immunohistochemistry was conducted to determine CSF-1R expression level in tumor specimens. Survival analysis was performed by the Kaplan-Meier method. Cox regression models were used to evaluate the impact of prognostic factors on CSS. A concordance index was calculated to measure prognostic accuracy. A prognostic nomogram was constructed on the basis of the identified independent prognostic factors. Results: CSF-1R expression in tumor tissues was higher than in peritumor tissues in 71.4 % (5 of 7) patients. CSF-1R expression of tumor tissues was positively associated with metastasis, tumor, node, metastasis classification system (TNM) stage, Eastern Cooperative Oncology Group performance status score and poor CSS. CSF-1R expression was determined as an independent prognostic factor for CSS in patients with ccRCC. Furthermore, extension of the well-established prognostic models with CSF-1R expression presented significantly improved prognostic accuracy. An efficient prognostic nomogram was constructed on the basis of the independent prognostic factors. Conclusions: High CSF-1R expression is a potential independent adverse prognostic factor for CSS in patients with ccRCC.
    No preview · Article · Oct 2015 · Annals of Surgical Oncology
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    ABSTRACT: 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). 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. 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 10years. CXCR2 is a potential independent adverse prognostic biomarker for recurrence and survival of patients with non-metastatic ccRCC after nephrectomy. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Jul 2015 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: The P2X7 receptor, an ATP-gated plasma membrane ion channel, involves in inflammation, apoptosis and cell proliferation, and thereby playing 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 6 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 score (P = 0.021) and 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Preview · Article · Jul 2015 · Cancer Science
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    ABSTRACT: 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). 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Urologic Oncology
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    ABSTRACT: Interleukin-4 (IL-4) and IL-13 are anti-inflammatory and immunoregulatory cytokines that can influence cancer-directed immunosurveillance. However, they are not evaluated as biomarkers for ccRCC outcomes. The aim of this study was to investigate the prognostic value of tumor-derived IL-4 and IL-13 in patients with localized ccRCC after surgery. Our study comprised 194 consecutive patients with localized ccRCC undergoing nephrectomy in a single center. Clinical characteristics, recurrence-free survival (RFS) and overall survival (OS) were recorded. We assessed IL-4 and IL-13 expression as continuous variables and dichotomized as low versus high by immunohistochemistry. For associations with RFS and OS, we used the Kaplan-Meier method and Cox regression models. Concordance index was calculated for predictive accuracy. We found that high expression levels of IL-4 and IL-13 were associated with increased recurrence (P < 0.001 and P = 0.006, respectively) and reduced survival (P = 0.001 and P = 0.016, respectively). Furthermore, multivariate analyses confirmed that combination of IL-4 and IL-13 expression (IL-4/IL-13 signature) was an independent prognostic factor for RFS and OS (P = 0.009 and P = 0.016, respectively). When applied to UISS score, IL-4/IL-13 signature improved the predictive accuracy. Notably, this improvement in prediction was mainly observed in patients with low-risk disease. To conclude, IL-4/IL-13 signature is an independent predictor of outcomes in patients with localized ccRCC, and the prognostic value is more prominent among patients with low-risk disease. Evaluation of IL-4 and IL-13 expression provides the opportunity to optimize postsurgical management and develop novel targeted therapies for ccRCC patients.
    No preview · Article · May 2015 · International journal of clinical and experimental pathology
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    ABSTRACT: p21-Activated kinase 4 (PAK4), a serine/threonine kinase implicated in the cytoskeleton organization to orchestrate cell morphology, adhesion, and motility, is associated with angiogenesis and vessel branching, which are important events in the progression of clear cell renal cell carcinoma (ccRCC). We investigated the effect of PAK4 expression on recurrence and survival among patients with nonmetastatic ccRCC following surgery. PAK4 expression was assessed, using immunohistochemistry, in 376 patients with nonmetastatic ccRCC after nephrectomy, where data of 187 patients were obtained from 2013 to 2014 and of 189 patients were obtained from 2008. Kaplan-Meier and Cox regression analyses were used to associate PAK4 expression with overall survival and recurrence-free survival. Overall, 41.2% and 36.5% of specimens exhibited high PAK4 expression in 2 cohorts. Patients with high PAK4 expression were prone to possess high Fuhrman grade and tumor necrosis. Moreover, high PAK4 intensity was significantly associated with poor overall survival and recurrence-free survival. PAK4 expression remained an independent adverse prognosticator after adjusting for other well-established factors. Furthermore, in subgroups stratified by Fuhrman grade or T category, patients with high PAK4 intensity had an increased risk of recurrence and death. After adjusting for age, high PAK4 expression was an adverse prognostic marker in subgroup of low Fuhrman grade and in subgroup of early T category. PAK4 expression is an independent adverse prognostic biomarker for recurrence and survival among patients with low-risk ccRCC after nephrectomy. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Urologic Oncology
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    ABSTRACT: The family of type 2 purinergic (P2) receptors, especially P2X7, is responsible for the direct tumor-killing functions of extracellular adenosine triphosphate (ATP), but the precise role of P2X7 in the progression of hepatocellular carcinoma (HCC) remains elusive. This study aims to evaluate prognostic value of P2X7 expression in HCC patients after surgical resection. Expression of P2X7 was assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissues from 273 patients with HCC who had undergone hepatectomy between 2006 and 2007. Prognostic value of P2X7 expression and clinical outcomes were evaluated. Peritumoral P2X7 expression was significantly higher than intratumoral P2X7 expression. No significant prognostic difference was observed for overall survival for intratumoral P2X7 density, whereas peritumoral P2X7 density indicates unfavorable overall survival in training set and BCLC stage 0-A subset. Besides, peritumoral P2X7 density, which correlated with tumor size, venous invasion, and BCLC stage, was identified as an independent poor prognosticator for overall survival and recurrence-free survival. The association was further validated in validation set. Peritumoral P2X7 is a potential unfavorable prognosticator for overall survival and recurrence free survival in HCC patients after surgical resection. Further external validation and functional analysis should be pursued to evaluate its potential prognostic value and therapeutic significance for HCC patients.
    No preview · Article · Feb 2015 · Tumor Biology
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    ABSTRACT: Galectin-9 (Gal-9), a member of animal lectin family with evolutionary conserved carbohydrate recognition domains, has been reported to exert a large variety of functional roles in tumorigenesis due to its β-galactoside-binding affinity. The aim of this study is to evaluate the expression and prognostic significance of Gal-9 in patients with clear-cell renal cell carcinoma (ccRCC). The expression of Gal-9 was assessed by immunohistochemistry in 196 patients with ccRCC who underwent nephrectomy. In the cohort, 48 patients died and 61 patients suffered recurrence. Kaplan-Meier method with log-rank test was applied to compare survival curves. The authors employed univariate and multivariate Cox regression models to evaluate the prognostic value of Gal-9 expression in overall survival (OS) and recurrence-free survival (RFS). In patients with ccRCC, Gal-9 expression, which was positively associated with tumor size (P = 0.014), Fuhrman grade (P = 0.010), and necrosis (P = 0.025), was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 2.394; P = 0.005) and RFS (HR 2.096; P = 0.006). High expression of Gal-9 was associated with poor survival (P = 0.001) and early recurrence (P = 0.006). Furthermore, Gal-9 expression could significantly stratify the patients in early (grades I + II) tumor, node, and metastasis (TNM) stage (OS: P = 0.005; RFS: P = 0.041) and low (grades 1 + 2) Fuhrman grade (OS: P = 0.004; RFS: P = 0.006). The prognostic accuracy of TNM, SSIGN, and UISS prognostic models was improved when Gal-9 expression was added. Gal-9 expression is a potential independent prognostic factor for OS and RFS in patients with ccRCC.
    No preview · Article · Feb 2015 · Tumor Biology
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    ABSTRACT: To estimate the impact of p21-activated kinase 1 expression on recurrence and survival of patients with non-metastatic clear cell renal cell carcinoma after surgical resection. We retrospectively enrolled 254 patients (187 in the training cohort and 67 in the validation cohort) with non-metastatic clear cell renal cell carcinoma undergoing nephrectomy at a single institution. Clinicopathological features, overall survival and recurrence-free survival were recorded. p21-activated kinase 1 intensities were assessed by immunohistochemistry of patients' specimens. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy. In both cohorts, elevated p21-activated kinase 1 expression in tumor tissues positively correlated with advanced T stage and Fuhrman grade. High p21-activated kinase 1 expression indicated poor survival and early recurrence of patients with non-metastatic clear cell renal cell carcinoma, especially with early T1-2 stage disease. After backward elimination, p21-activated kinase 1 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of the traditional University of California Integrated Staging System and Mayo Clinic stage, size, grade and necrosis prognostic models was improved when p21-activated kinase 1 expression was added. Elevated expression of p21-activated kinase 1 seems to be an independent adverse prognostic biomarker for recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma after nephrectomy. © 2015 The Japanese Urological Association.
    No preview · Article · Feb 2015 · International Journal of Urology
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    ABSTRACT: Interleukin-11 (IL-11), a member of the IL-6 family of cytokines, exerts pleiotropic oncogenic activities by stimulating angiogenesis and metastasis in many cancer types. Our present study aims to evaluate the impact of IL-11 expression on recurrence and mortality of patients with clear-cell renal cell carcinoma (ccRCC). We retrospectively enrolled 193 ccRCC patients undergoing nephrectomy at a single center. Clinicopathologic features, recurrence-free survival (RFS) and overall survival (OS) were recorded. IL-11 intensity was assessed by immunohistochemistry in tumor specimens. Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on RFS and OS. Concordance index (C-index) was calculated to assess predictive accuracy. High IL-11 expression is associated with increased risk of recurrence and poor survival for ccRCC patients (P < 0.001 and P < 0.001, respectively), especially those with early-stage disease (TNM stage I + II). Multivariate analyses confirmed that IL-11 expression was an independent prognostic factor for RFS and OS (P = 0.006 and P = 0.008, respectively). The predictive accuracy of well-established prognostic models was improved when IL-11 expression was integrated. In conclusion, high IL-11 expression is an independent predictor of poor prognosis in ccRCC patients. It may help identify patients who could benefit from additional treatments and closer follow-up. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Feb 2015 · Cancer Science
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    ABSTRACT: To evaluate the prognostic significance of Notch1 activation in patients with clear-cell renal cell carcinoma (ccRCC). We retrospectively enrolled 203 patients with ccRCC undergoing nephrectomy at Zhongshan Hospital of Fudan University between 2003 and 2004. Notch1 activation was assessed by immunohistochemical staining of the intracellular domain of Notch1 (ICN1) in specimens of patients. The Kaplan-Meier method, Cox regression models, and Harrell concordance index (C-index) calculation were used to evaluate the prognostic value of ICN1 expression and its association with clinicopathologic features. Tumor tissues from patients with advanced TNM stage and Fuhrman grade exhibited elevated ICN1 expression, which correlated positively with tumor size, Fuhrman grade, and tumor necrosis. Moreover, high ICN1 expression indicated poor overall survival and recurrence-free survival of patients with ccRCC. After backward elimination, ICN1 expression, as well as Fuhrman grade, Eastern Cooperative Oncology Group performance status, and TNM stage, was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of well-established TNM, University of California Integrated Staging System, and Mayo Clinic stage, size, grade, and necrosis prognostic models was improved when ICN1 expression was added. Furthermore, a predictive nomogram was generated with identified independent prognosticators to assess patient survival at 5 years after surgery. Notch1 activation is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · Urology
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    ABSTRACT: To investigate the prognostic value of interleukin-11 receptor α chain in patients with early-stage clear-cell renal cell carcinoma. Interleukin-11 receptor α chain, a member of the gp130-dependent receptors, exerts pleiotropic oncogenic activities by promoting proliferation, angiogenesis and metastasis in many cancers. We retrospectively enrolled 293 patients (130 in the training cohort and 163 in the validation cohort) with early-stage (TNM Stage I + II) clear-cell renal cell carcinoma undergoing nephrectomy at a single institution. Clinicopathologic features, recurrence-free survival and overall survival were recorded. Interleukin-11 receptor α chain intensities were assessed by immunohistochemistry in tumor tissues. Kaplan-Meier method was applied to compare survival curves between groups. Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival and overall survival. The concordance index was calculated to assess predictive accuracy. In both training and validation cohorts, high interleukin-11 receptor α chain expression was associated with early recurrence (P = 0.004 and P = 0.015, respectively) and poor survival (P < 0.001 and P = 0.019, respectively) of patients with early-stage clear-cell renal cell carcinoma. Multivariate analyses confirmed that interleukin-11 receptor α chain expression was an independent prognostic factor for recurrence-free survival (P = 0.004) and overall survival (P = 0.001). The predictive accuracy of the Leibovich prognostic score was improved when interleukin-11 receptor α chain expression was incorporated. Notably, the improvement in prediction mainly took place in patients with low-risk disease defined by the Leibovich score. High Interleukin-11 receptor α chain expression is an independent predictor of poor clinical outcome in patients with early-stage clear-cell renal cell carcinoma, and the prognostic value is more prominent in those with low-risk disease. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Preview · Article · Nov 2014 · Japanese Journal of Clinical Oncology
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    ABSTRACT: Galectin-8 (Gal-8), belonging to a family of the "tandem repeat"-type galectins that contain 2 carbohydrate recognition domains, serves to retain cell surface residency and signaling of glycoproteins including cytokine and growth factor receptors, and thereby promoting development and progression of various malignancies. This study aims to evaluate the effect of Gal-8 expression on postoperative recurrence of patients with localized pathologic T1 (pT1) clear cell renal cell carcinoma (ccRCC). In this retrospective study, we enrolled 244 patients (122 in group A and 122 in group B) with localized pT1 ccRCC undergoing nephrectomy at a single institution. Specimens from patients were collected from January 2003 to December 2008. Median follow-up was 71 months (range: 12-120mo) in group A and 70 months (range: 12-119mo) in group B. Overall, 14 patients experienced recurrence in group A (n = 122) and 22 patients had recurrence in group B (n = 122). Gal-8 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 recurrence-free survival. Concordance index was calculated to assess prognostic accuracy. In both groups, patients with high expression of Gal-8 were significantly inclined to have high rates of necrosis. High Gal-8 expression indicated early recurrence of patients with localized pT1 ccRCC. Gal-8 expression was determined to be an independent adverse prognostic indicator for recurrence. The accuracy of The Mayo Clinic Stage, Size, Grade, and Necrosis score and University of Los Angeles Integrated Staging System prognostic models was improved when Gal-8 expression was added. Gal-8 expression is a potential independent unfavorable prognostic indicator for postoperative recurrence of patients with localized pT1 ccRCC. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014 · Urologic Oncology

Publication Stats

175 Citations
122.66 Total Impact Points

Institutions

  • 2015
    • Ruijin Hospital North
      Shanghai, Shanghai Shi, China
  • 2010-2015
    • Fudan University
      • Department of Biochemistry and Molecular Biology
      Shanghai, Shanghai Shi, China