共查询到20条相似文献，搜索用时 109 毫秒
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Yuji Miura Naoko Inoshita Masaomi Ikeda Yu Miyama Ryosuke Oki Suguru Oka Chihiro Kondoh Yukinori Ozaki Yuko Tanabe Kazuhiro Kurosawa Shinji Urakami Tadasu Kohno Toshikazu Okaneya Toshimi Takano 《Urologic oncology》2017,35(6):386-391
Objectives
To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value.Methods and materials
We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS).Results
The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58–136) and 51 months (95% CI: 13–82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42–97) and 120 (95% CI: 52–120) months, respectively (P = 0.25).Conclusion
Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC. 相似文献3.
Daniel M. Tennenbaum Brandon J. Manley Emily Zabor Maria F. Becerra Maria I. Carlo Jozefina Casuscelli Almedina Redzematovic Nabeela Khan Maria E. Arcila Martin H. Voss Darren R. Feldman Robert J. Motzer Nicole E. Benfante Jonathan A. Coleman Paul Russo James J. Hsieh Abraham Ari Hakimi 《Urologic oncology》2017,35(8):532.e7-532.e13
Purpose
To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC).Materials and methods
We identified 60 patients who presented with metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL, PBRM1, BAP1, SETD2, and KDM5C. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test was used for comparisons between groups.Results
Median OS in the cohort was 2.5 years. Higher Fuhrman grade was associated with decreased median OS (P<0.001). Mutations in SETD2 (P = 0.027) and KDM5C (P = 0.019) were associated with reduced risk of death (hazard ratio [HR] = 0.58 [95% CI: 0.35–0.94] and HR = 0.43 [95% CI: 0.22–0.85], respectively). BAP1 mutations (P = 0.008) were associated with increased risk of death (HR = 1.81 [95% CI: 1.16–2.83]). There were significantly more female patients with a BAP1 mutation than females in the overall cohort (P = 0.001).Conclusions
Mutations in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our results expand upon efforts at understanding genomic biomarkers in localized disease. Those efforts set the stage for our novel investigation examining associations of select recurrent somatic mutations in stage IV patients with ccRCC. 相似文献4.
Ning Liu Daoguang Huang Xiangming Cheng Yankun Chong Wei Wang Weidong Gan Hongqian Guo 《Urologic oncology》2017,35(8):530.e1-530.e6
Objectives
To compare the clinical outcomes of percutaneous radiofrequency ablation (PRFA) and partial nephrectomy (PN) in patients with clear cell renal cell carcinoma (ccRCC) and non–clear cell RCC (nccRCC) of the most common subtypes.Materials and methods
A retrospective study was conducted to review the records of all the patients who underwent PRFA or PN between February 2005 and April 2014 at our institution. Patients with histologic confirmation of ccRCC, papillary RCC, and chromophobe RCC were included. The Mann-Whitney U test was applied to compare PRFA to PN in the ccRCC and nccRCC groups. The Kaplan-Meier method was used to generate the survival curves that were compared to the log-rank test.Results
A total of 264 patients meeting the selection criteria were included in this study. The tumor size ranged from 0.9 to 7.0 cm. The median follow-up period was 78 months (range: 8–132 mo). Although PRFA provided comparable 10-year overall survival rates and 10-year disease-free survival (DFS) rates to PN both in ccRCC ≤4 cm and nccRCC, the 10-year DFS for patients treated with PRFA was lower than that of PN in ccRCC >4 cm. The DFS survival curve between the 2 operations and 2 subtypes was statistically significant in patients with tumor size >4 cm. Limitations include retrospective review and selection bias.Conclusions
Patients with T1b ccRCC treated with PRFA have less favorable outcomes than those with PN whereas PRFA provides comparable oncologic outcomes to PN in patients with T1b nccRCC. It is necessary to take RCC subtypes into consideration when choosing a surgical approach to treat T1b RCC between PFRA and PN. 相似文献5.
Zhenwei Lei Xin Ma Hongzhao Li Yu Zhang Yu Gao Yang Fan Xintao Li Luyao Chen Yongpeng Xie Jianwen Chen Shengpan Wu Lu Tang Xu Zhang 《Urologic oncology》2018,36(3):93.e23-93.e37
Objectives
Dysregulated expression of miR-181a accompanies tumorigenesis in many human cancers. However, in clear cell renal cell carcinoma (ccRCC), the role of miR-181a remains unclear. The aim of this study was to investigate biological functions of miR-181a and its expression levels in ccRCC tissues and cancer cell lines.Material and methods
Expression levels of miR-181a in samples of ccRCC tumors and adjacent nontumor tissues from 42 patients as well as in 786-O, 769-P, A498, and CAKI-1 ccRCC cell lines were determined by quantitative real-time polymerase chain reaction. Potential targets of miR-181a were predicted using bioinformatic approaches and then verified by using the luciferase reporter assay. The effects of miR-181a on cell proliferation, colony formation, cell cycle progression, and apoptosis were investigated in ccRCC cell lines transfected with specific miR-181a mimic and inhibitor.Results
We found that miR-181a expression was up-regulated in ccRCC tissues and cell lines. The expression level of miR-181a significantly correlated with the tumor size, tumor/node/metastasis staging, and Fuhrman grade. Luciferase assays showed that KLF6 was a target of miR-181a. KLF6 expression was inversely correlated with the level of miR-181a. Overexpression of miR-181a led to reduced KLF6 mRNA and protein levels, whereas mutations of the potential miR-181a binding sites in the KLF6 gene abrogated this inhibitory effect. Furthermore, overexpression of miR-181a promoted proliferation and G1/S cell cycle transition, as well as inhibited apoptosis by down-regulating KLF6 in ccRCC cells.Conclusions
miR-181a is up-regulated in ccRCC and may act as a tumor promoting factor by targeting KLF6 expression. Manipulating miR-181a may provide a beneficial effect in the treatment of ccRCC. 相似文献6.
Solène-Florence Kammerer-Jacquet Angelique Brunot Karim Bensalah Boris Campillo-Gimenez Mathilde Lefort Sahar Bayat Alain Ravaud Frantz Dupuis Mokrane Yacoub Gregory Verhoest Benoit Peyronnet Romain Mathieu Alexandra Lespagnol Jean Mosser Julien Edeline Brigitte Laguerre Jean-Christophe Bernhard Nathalie Rioux-Leclercq 《Urologic oncology》2017,35(10):603.e7-603.e14
Introduction
The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib.Materials and methods
In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect.Results
HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival.Conclusion
HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. 相似文献7.
Yuan Chang Lin Zhou Le Xu Qiang Fu Yuanfeng Yang Zongming Lin Jiejie Xu 《Urologic oncology》2017,35(12):675.e17-675.e24
Purpose
Accumulating evidence indicates that CXC chemokine receptor 6 (CXCR6) has a crucial role in cancer development and progression, however, its role in clear cell renal cell carcinoma (ccRCC) remains obscure. The aim of this study is to investigate the prognostic value of CXCR6 expression in patients with ccRCC following surgery.Materials and methods
This study retrospectively included 239 patients with ccRCC who underwent nephrectomy and had paraffin tissue available at a single center. CXCR6 expression in tumor tissue was evaluated by immunohistochemistry and its associations with overall survival (OS) and recurrence-free survival (RFS) were investigated.Results
A total of 47.3% tumors were considered as high expression of CXCR6, which was significantly associated with the male sex (P = 0.003) and high Fuhrman grade (P<0.001). A high expression of CXCR6 indicated a reduced OS (P<0.001) and RFS (P = 0.007). Multivariate analysis demonstrated that CXCR6 expression was an independent prognostic factor of OS (hazard ratio = 2.604; 95% CI: 1.338–5.068; P = 0.005) and RFS (hazard ratio = 1.957; 95% CI: 1.065–3.595; P = 0.031). Subgroup analysis found that CXCR6 expression could differentiate survival risks among patients with high-risk disease. Moreover, a nomogram integrating CXCR6 expression and traditional clinical and pathologic features was established and predicted postsurgical recurrence-risk well at 3- and 5-year.Conclusions
The expression of CXCR6 in tumor tissue may serve as a potential prognostic biomarker to refine clinical prognosis prediction combined with traditional clinical and pathological analysis for patients with ccRCC after surgery. 相似文献8.
Yan-Wei Cao Yong Liu Zhen Dong Lei Guo En-Hao Kang Yong-Hua Wang Wei Zhang Hai-Tao Niu 《Urologic oncology》2018,36(6):311.e15-311.e25
Background
Prognostic biomarkers for patients with clear cell renal cell carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis, are not well established. In this study, we examined the correlations of monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for glycolytic metabolism, with various clinicopathological parameters as well as survival of patients with ccRCC and those treated with vascular endothelial growth factor receptor (VEGFR) inhibitors.Methods
A cohort of 150 ccRCC patients were recruited into this study. All patients underwent radical or partial nephrectomy as the first-line treatment, and 38 received targeted therapy (sorafenib or sunitinib) after the surgery. Expression levels of MCT1, MCT4, and CD34 were examined by immunohistochemistry. Correlations between MCT1 or MCT4 expression and different clinicopathological parameters or patient survival were analyzed among all as well as patients receiving targeted therapy.Results
MCT1 or MCT4 expression did not significantly correlate with sex, age, tumor diameter, microvascular density, tumor staging, pathological Furmann grade, or MSKCC (P>0.05). High expression of either MCT1 or MCT4 significantly correlated with reduced overall survival (OS) and progression-free survival (PFS) among the total cohort of ccRCC patients. For patients receiving targeted therapy, high expression of either MCT1 or MCT4 significantly correlated with reduced PFS, but not OS. Both conditions were independent prognostic biomarkers for reduced PFS among all patients or those receiving targeted therapy.Conclusion
MCT1 and MCT4 are prognostic biomarkers for patients with ccRCC or those receiving targeted therapy. High expression of these 2 proteins predicts reduced PFS in these patients. 相似文献9.
Objectives
The aim of the study was to assess the association between the progression-free survival (PFS) and perirenal fat thickness (PFT) in a population of histopathologically confirmed, localized clear cell renal cell carcinoma (ccRCC) patients.Methods
We retrospectively enrolled 174 patients with localized ccRCC at our center between December 2009 and December 2015. The preoperative visceral fat area (VFA), PFT, and subcutaneous fat area (SFA) were evaluated. Kaplan-Meier curves were used to assess the differences in PFS between the high and the low PFT groups within sexes. Potential independent prognostic factors of PFS were identified by univariable and multivariable Cox analyses.Results
During the follow-up period (median, 38 months), 27 patients (21 with high PFT and 6 with low PFT) experienced tumor progression. Kaplan-Meier curves revealed that high PFT was associated with a worse PFS than low PFT (P = 0.005). In the univariable Cox analyses, high VFA, high PFT, T stage, and the presence of sarcomatoid differentiation were significantly associated with a poor PFS. Moreover, both high PFT and VFA retained significance in the multivariable analysis.Conclusion
We first report the evidence that high PFT presents as an independent risk factor of tumor progression in localized ccRCC. We suggest that this noninvasive and readily available preoperative parameter may help in the risk stratification of ccRCC patients before surgery. 相似文献10.
Chenzhang Ou Li Liu Jiajun Wang Siyuan Dai Yang Qu Ying Xiong Wei Xi Jiejie Xu Jianming Guo 《Urologic oncology》2017,35(10):607.e1-607.e8
Purpose
Sialic acid-binding immunoglobulin-like lectins (siglecs) family has important functions in tumor progression. The purpose of our study is to figure out the correlation between the expression level of Siglec-8 and prognosis of patients with clear cell renal cell carcinoma (ccRCC), and then to predict the overall survival (OS) via a novel nomogram.Materials and methods
A group of patients (n = 267) histologically diagnosed with ccRCC from Zhongshan Hospital were included into our study. Immunohistochemistry of Siglec-8 was performed in the tissue microarray, and the staining intensity was divided into high/low according to the median value of the H-score grading. Survival analyses including Kaplan-Meier analyses and Cox regression analyses were performed to evaluate the association between Siglec-8 expression and the survival of patients in different risk groups. Stage, size, grade, and necrosis score and University of California Los Angeles Integrated Staging System score were used in the risk stratification. A nomogram incorporating Siglec-8 and several other clinical parameters was plotted for predicting the 5-year and 8-year OS.Results
Siglec-8 was observed dominantly on the membrane of tumor cells. The enhanced expression level of Siglec-8 had significant correlation with adverse overall and disease-free survival of patients (P<0.0001 and P = 0.0186, respectively). The association was more significant in patients with lower risk. Cox regression analyses defined Siglec-8 as an independent prognostic factor of OS (P<0.001 for univariate analysis, P = 0.003 for multivariate analysis). The new nomogram integrating Siglec-8 with several traditional prognostic factors proved to be more accurate than conventional prognostic system using tumor node metastasis stage only (Harrell c-index: 0.801, 95% CI: 0.755–0.847 vs. 0.717, 95% CI: 0.662–0.772).Conclusion
Our study has found that the elevated expression level of Siglec-8 was correlated with poor prognosis of patients with ccRCC. Siglec-8, incorporation with other clinical parameters, could perform better in prediction of patients? OS. 相似文献11.
Giuseppe Lucarelli Monica Rutigliano Matteo Ferro Andrea Giglio Angelica Intini Francesco Triggiano Silvano Palazzo Margherita Gigante Giuseppe Castellano Elena Ranieri Carlo Buonerba Daniela Terracciano Francesca Sanguedolce Anna Napoli Eugenio Maiorano Franco Morelli Pasquale Ditonno Michele Battaglia 《Urologic oncology》2017,35(7):461.e15-461.e27
Objective
To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC).Materials and methods
The expression of KYN pathway components was investigated by tissue microarray-based immunohistochemistry, indirect immunofluorescence, and confocal microscopy analysis in 100 ccRCC cases and 30 normal renal samples. The role of this pathway in sustaining cancer cell proliferation, migration, and chemoresistance was evaluated. In addition, tryptophan and KYN concentrations and their ratio were measured in serum of 195 patients with ccRCC using a sandwich enzyme-linked immunosorbent assay. The role of KTR as a prognostic factor for ccRCC cancer-specific survival (CSS) and progression-free survival (PFS) was assessed.Results
Tissue microarray-based immunohistochemistry and indirect immunofluorescence staining showed an increased signal for KYN pathway components in ccRCC. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high vs. low KTR. In particular, patients with high KTR values had a 5-year survival rate of 76.9% as compared with 92.3% for subjects with low levels (P ?<?0.0001). Similar findings were observed for PFS (72.8% vs. 96.8% at 5 y). At multivariate analysis, KTR was an independent adverse prognostic factor for CSS (hazard ratio? =?1.24, P? = ?0.001), and PFS (hazard ratio? =? 1.14, P? =? 0.001).Conclusions
The involvement of the KYN pathway enzymes and catabolites in ccRCC occurs via both immune and nonimmune mechanisms. Our data suggest that KTR could serve as a marker of ccRCC aggressiveness and as a prognostic factor for CSS and PFS. 相似文献12.
Anica Högner Hans Krause Burkhard Jandrig Mumtaz Kasim Tom Florian Fuller Martin Schostak Andreas Erbersdobler Andreas Patzak Ergin Kilic 《Urologic oncology》2018,36(3):94.e1-94.e14
Objective
To identify the clinicopathological association of PBRM1 (Polybromo-1 gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in clear cell renal cell carcinoma (ccRCC) and its role in tumor progression.Patients and methods
Immunohistochemical analysis, Western blotting and qPCR analysis of PBRM1 and VHL were performed on fresh-frozen ccRCC and adjacent normal tissue obtained from 70 patients who underwent radical nephrectomy. In addition, a tissue microarray (TMA) from specimens of 326 ccRCC patients was used to evaluate the effect of loss of PBRM1 and VHL immunohistological expression on clinicopathological features as well as patient survival.Results
In frozen tissue, PBRM1 and VHL mRNA were significantly down-regulated in most ccRCC tumors (77.6%/80.6%). Simultaneous weak PBRM1 and VHL protein expression was observed in 21.4% of frozen tumors. In the TMA samples, weak PBRM1 and VHL immunohistochemical staining was observed in 60.4% of the cases and was correlated (P<0.001). The association of PBRM1 and VHL immunohistochemical expression with clinicopathological parameters depicts a variable picture: predominantly weak PBRM1 and VHL expression were significantly associated with higher Fuhrman grade (P = 0.012 and 0.024, respectively) but only weak VHL expression was associated with a higher pT stage (P = 0.023). PBRM1 expression did not affect the overall survival, whereas weak VHL expression was associated with decreased patient overall survival (P = 0.013).Conclusions
Our data suggest that reduced expression of PBRM1 and VHL is correlated with an increased tumor aggressiveness. Low VHL expression was identified as a risk factor for worse patient overall survival, independently from PBRM1 expression pattern. 相似文献13.
Vesna M. Coric Tatjana P. Simic Tatjana D. Pekmezovic Gordana M. Basta-Jovanovic Ana R. Savic-Radojevic Sanja M. Radojevic-Skodric Marija G. Matic Sonja R. Suvakov Dejan P. Dragicevic Tanja M. Radic Zoran M. Dzamic Marija S. Pljesa-Ercegovac 《Urologic oncology》2017,35(6):409-417
Purpose
Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC).Methods
GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot.Results
We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (P<0.05). On the contrary, survival analysis indicated shorter overall survival for patients with ccRCC with GSTM1-active genotype (P = 0.026). Furthermore, patients with ccRCC with GSTM1-active genotype had significantly higher hazard ratio (P<0.05), in analyzed regression models, compared with the carriers of GSTM1-null genotype. Finally, the presence of GSTM1:ASK1 protein-protein interaction was found in all RCC tissue samples studied.Conclusions
Carriers of GSTM1-null and GSTP1-variant genotypes are in increased risk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis. 相似文献14.
William P. Parker Christine M. Lohse Harras B. Zaid John C. Cheville Stephen A. Boorjian Bradley C. Leibovich R. Houston Thompson 《Urologic oncology》2017,35(1):36.e1-36.e6
Objectives
Beta-blocker use is associated with improved survival for multiple nonurologic malignancies. Our objective was to evaluate the association between beta-blocker use and survival among surgically managed hypertensive patients with clear-cell renal cell carcinoma (ccRCC).Methods
Hypertensive patients with ccRCC treated with either radical or partial nephrectomy between 2000 and 2010 were identified from our Nephrectomy Registry. Beta-blocker use within 90 days before surgery was identified. The associations between beta-blocker use and risk of disease progression, death from renal cell carcinoma (RCC), and all-cause mortality were assessed using Cox proportional hazards regression models.Results
In total, 913 hypertensive patients were identified who underwent either partial or radical nephrectomy for ccRCC. Of these, 104 (11%) had documented beta-blocker use within 90 days before surgery. At last follow-up (median 8.2 y among survivors), 258 patients showed progression (median 1.6 y following surgery), and 369 patients had died (median 4.1 y following surgery), including 138 who died of RCC. After adjusting for PROG (progression-free survival) and SSIGN (cancer-specific survival) scores, beta-blocker use was not significantly associated with the risk of disease progression (hazard ratio [HR] = 0.94; 95% CI: 0.61–1.47; P = 0.80) or the risk of death from RCC (HR = 0.74; 95% CI: 0.38–1.41; P = 0.35). Similarly, on multivariable analysis adjusting for clinicopathologic features, there was not a significant association between beta-blocker use and the risk of all-cause mortality (HR = 0.83; 95% CI: 0.59–1.16; P = 0.27).Conclusions
Beta-blocker use for hypertension within 90 days before surgery was not associated with the risk of progression, death from RCC, or death from any cause. 相似文献15.
Fan Zhang Xin Ma Huizi Li Gang Guo Pengfei Li Hongzhao Li Liangyou Gu Xintao Li Luyao Chen Xu Zhang 《Urologic oncology》2017,35(6):392-400
Objectives
To investigate the predictive and prognostic values of the logistic regression model based on the serum amino acid levels.Materials and methods
The study enrolled 42 patients with clear cell renal cell carcinoma (ccRCC) and 66 matched healthy people admitted to PLA General Hospital from April 2015 to June 2015. Serum samples from the 2 groups were analyzed by isobaric tags for relative and absolute quantitation-liquid chromatography-tandem mass spectrometry (iTRAQ-LC-MS/MS) method. Variables of the 2 groups were compared by Student’s t-test or chi-square test. The prediction model was constructed by logistic regression analysis. Oncological outcomes were evaluated by Kaplan-Meier survival analysis and Cox regression analysis.Results
Pathological diagnosis confirmed that all patients had ccRCC. No significant differences were found in the distribution of age, sex, or body mass index between patients with ccRCC and matched healthy people. A total of 32 amino acids were quantitatively analyzed, and serum levels of 23 amino acids were significantly different between the 2 groups. A predictive logistic regression model containing histidine, glutamine, 1-methyl histidine, and norvaline was constructed. Receiver operating characteristic (ROC) curves for all patients with ccRCC and controls, patients with T1 ccRCC and controls, patients with Fuhrman grade 1 to 2 ccRCC and controls, patients with T2 ccRCC and controls, and patients with Fuhrman grade 3 ccRCC and controls were drawn based on the model. The area under the curve values of the 5 receiver operating characteristic curves were 0.878, 0.885, 0.890, 0.830, and 0.788, respectively. Patients with higher model scores (>2) had significantly poorer progression-free survival (PFS) than patients with lower model scores (≤2). Multivariable Cox regression analysis showed that logistic regression model score was an independent predictor of PFS.Conclusion
Serum amino acid levels are a potential predictive biomarker for distinguishing patients with ccRCC, especially early T-stage and low Fuhrman grade patients, from healthy people. Serum amino acid levels can also be used in the prognostic evaluation of patients with ccRCC. 相似文献16.
17.
Xiang Chen Li Liu Jiajun Wang Zhiyuan Lin Ying Xiong Yang Qu Zewei Wang Yuanfeng Yang Jianming Guo Jiejie Xu 《Urologic oncology》2018,36(5):242.e15-242.e21
Purpose
CXCR1 signaling promotes tumor progression in various cancers, and clinical trial has proved efficacy of CXCR1 inhibitor in metastatic breast cancer. Therefore, we investigated the prognostic value of CXCR1 in patients with metastatic renal cell carcinoma (mRCC) receiving tyrosine kinase inhibitors (TKIs) therapy.Materials and Methods
Patients treated with sunitinib or sorafenib were retrospectively enrolled (n = 111). CXCR1 expression was assessed by immunohistochemical staining of tissue microarrays of primary tumor, and its association with prognosis and therapeutic response were evaluated. To explore possible mechanism related to CXCR1 expression, gene set enrichment analysis was performed based on The Cancer Genome Atlas cohort.Results
High CXCR1 expression was associated with poorer overall survival (P = 0.015) and was an independent prognostic factor for patients with mRCC treated by TKIs (Hazard Ratio = 1.683, 95% Confidence Interval: 1.109–2.553, P = 0.014). CXCR1 expression was also associated with worse therapeutic response of TKIs (P = 0.017). Thirteen pathways, including hypoxia and angiogenesis, were identified to be enriched in CXCR1 positive patients.Conclusions
High CXCR1 expression indicates reduced benefit from TKIs therapy in patients with mRCC. The mechanism may be attributed to the enriched pathways of hypoxia and angiogenesis in CXCR1 positive patients. CXCR1 may be a potential therapeutic target for mRCC, but further studies are required. 相似文献18.
Walter Henriques da Costa Aline Fusco Fares Stephania M. Bezerra Mariana A Morini Ligia Alencar de Toledo Benigno Diego Abreu Clavijo Lucas Fornazieri Maurício Murce Rocha Isabela Werneck da Cunha Stenio de Cassio Zequi 《Urologic oncology》2019,37(1):78-85
Purpose
To evaluate the prognostic impact of the protein expression of both PBRM1 and BAP1 in metastatic tissue of patients with metastatic clear cell renal cell carcinoma (ccRCC).Patients and methods
In all 124 consecutive cases of metastatic ccRCC, who underwent metastasectomy or biopsy of metastatic tumor tissue between 2007 and 2016 were selected from the medical records of our institution. Additionally, 38 paired cases with tissue from the primary tumor involving radical or partial nephrectomy for ccRCC were also selected. All cases were reviewed for uniform reclassification and the most representative tumor areas were selected for the construction of a tissue microarray.Results
PBRM1 nuclear staining of the 124-immunostained metastases of ccRCC specimens showed that 98 (79.0%) had negative expression and 26 (21.0%) positive expression of PBRM1. Regarding BAP1 expression, we observed that 77 (62.1%) specimens were negative and 47 (37.9%) showed positive nuclear staining. When we compared the expression of both markers on primary tumor and tumor metastasis, we found disagreement in half of the cases. Five-year overall survival rates in patients with positive expression and negative expression of BAP1 were 53.2% and 35.1%, respectively (P?=?0.004). Five-year progression-free survival rates in patients with positive expression and negative expression of BAP1 were 14.9% and 3.9%, respectively (P?=?0.003). Conversely, PBRM1 expression did not significantly influence either overall survival or progression-free survival rates. In multivariate analysis, negative expression of BAP1 tumors also presented higher risks of death (hazard ratio (HR)?=?1.913, P?=?0.041) and disease progression (HR?=?1.656, P?=?0.021).Conclusion
The use of prognostic biomarkers identified in the primary tumor tissue might be not reliable in the metastatic disease scenario. Patients with metastatic ccRCC that present loss of BAP1 expression in metastatic tissue demonstrated poor survival rates and represent a relevant risk group for tumor recurrence and death. 相似文献19.
Luís Eduardo Zucca Mariana Andozia Morini Matushita Renato José da Silva Oliveira Cristovam Scapulatempo-Neto Marcos Alves de Lima Guilherme Gomes Ribeiro Cristiano Ribeiro Viana Flavio Mavignier Cárcano Rui Manuel Reis 《Urologic oncology》2018,36(1):11.e13-11.e21
Background
Renal cell carcinoma (RCC) represents 2%–3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib.Objective
To study the expression of AXL in a series patients with of mRCC treated with sunitinib and to correlate it with patient's clinic-pathological features and therapeutic response.Material and methods
Sixty-four patients with mRCC (51 clear cell carcinomas (CCCs) and 13 non-CCCs) were evaluated for AXL expression by immunohistochemistry in the primary tumor.Results
AXL positivity was observed in 47% (30/64) of cases, namely in 43% (22/51) of CCCs and 61% (8/13) of non-CCC. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, Karnofsky performance status, more than 1 site of metastasis and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Overall, the multivariate survival analysis showed that absence of nephrectomy (HR = 4.85, P = 0.001), more than 1 site of metastasis (HR = 2.99, P = 0.002), bone metastasis (HR = 2.95, P = 0.001), together with AXL expression (HR = 2.01, P = 0.048) were independent poor prognostic factor in patients with mRCC.Conclusion
AXL expression was associated with worse clinical outcome and may be an important prognostic biomarker in sunitinib-treated patients with metastatic renal cell carcinoma. 相似文献20.
Hsiang-Lin Lee Hui-Ling Chiou Shian-Shiang Wang Sheng-Chun Hung Ming-Chih Chou Shun-Fa Yang Ming-Ju Hsieh Ying-Erh Chou 《Urologic oncology》2018,36(4):160.e15-160.e21