A novel preoperative inflammatory marker prognostic score in patients with clear cell and non-clear cell renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 530-530
Author(s):  
Rishi Robert Sekar ◽  
Dattatraya Patil ◽  
Jeff Pearl ◽  
Yoram Baum ◽  
Omer Kucuk ◽  
...  

530 Background: Several inflammatory markers have been studied as potential biomarkers in clear cell renal cell carcinoma (RCC), however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies. We hypothesize that a combination of preoperative C-Reactive Protein (CRP), albumin, Erythrocyte Sedimentation Rate (ESR), corrected calcium, and AST/ALT ratio into a RCC Inflammatory Score (RISC) could serve as a rigorous prognostic indicator in patients with clear cell and non-clear cell RCC. Methods: Patients that underwent nephrectomy for localized RCC were queried from our nephrectomy database. The optimal threshold for individual biomarkers was determined using grid search methodology, receiver operating characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. The final score, RISC, was the sum of points accrued from each biomarker (Table). ROC and chi-square analysis was performed to compare the prognostic ability of RISC to SSIGN and UISS. Impact on overall survival was analyzed with multivariate logistic regression analysis. Results: 391 patients were included in the study. Area under the curve (AUC) for RISC, SSIGN, and UISS was 0.78, 0.78, and 0.81, respectively. Chi-square analysis of AUCs revealed no statistically significant difference between RISC, SSIGN, and UISS (p= 0.820, and p =0.317, respectively). On multivariate analysis, after adjusting for confounding variables, each unit increase in RISC was associated with a 32% increase in mortality (HR=1.32, 95%CI 1.17-1.49, p<0.001). Conclusions: RISC is an independent and significant predictor of overall survival in clear cell and non-clear cell RCC with accuracy at least as good as other established prognostic tools. Notably, RISC is composed of standardized preoperative laboratory markers, allowing crucial prognostic information to be integrated into medical decision making prior to surgery. [Table: see text]

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 566-566
Author(s):  
Rishi Robert Sekar ◽  
Dattatraya Patil ◽  
Jeff Pearl ◽  
Yoram Baum ◽  
Omer Kucuk ◽  
...  

566 Background: Several inflammatory markers have been singularly studied as potential biomarkers in clear cell renal cell carcinoma (RCC), however few reports have analyzed their prognostic value in aggregate. We hypothesize that a combination of preoperative C-Reactive Protein (CRP), albumin, Erythrocyte Sedimentation Rate (ESR), corrected calcium, and AST/ALT ratio into a RCC Inflammatory Score (RISC) could serve as a rigorous prognostic indicator in patients with clear cell RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC were queried from our nephrectomy database. The optimal threshold for individual biomarkers was determined using grid search methodology, receiver operating characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. The final score, RISC, was the sum of all points accrued from each biomarker (Table). ROC and chi-square analysis was performed to compare the prognostic ability of RISC to SSIGN and UISS. Impact on overall survival was analyzed with multivariate logistic regression analysis. Results: 280 patients were included in the study. Area under the curve (AUC) for RISC, SSIGN and UISS was 0.77, 0.78, and 0.81, respectively. Chi-square analysis of AUCs revealed no statistically significant difference between RISC, SSIGN, and UISS (p= 0.975 and p =0.299, respectively). On multivariate analysis, after adjusting for confounding variables, each unit increase in RISC was associated with a 31% increase in mortality (HR=1.31, 95%CI 1.13-1.50, p<0.001). Conclusions: RISC is an independent and significant predictor of overall survival in clear cell RCC with accuracy at least as good as other established prognostic tools. Notably, RISC is composed of standardized laboratory markers easily and cost-effectively obtained preoperatively, allowing crucial prognostic information to be integrated into medical decision making prior to surgery. [Table: see text]


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 690-690
Author(s):  
Dattatraya H Patil ◽  
Sierra Williams ◽  
Mersiha Torlak ◽  
Mehrdad Alemozaffar ◽  
Aaron Lay ◽  
...  

690 Background: Multiple inflammatory markers have been evaluated in predicting preoperative risk in patient’s undergoing curative nephrectomy for Clear cell renal cell carcinoma. We propose that ratio of C-Reactive Protein to albumin (CA-ratio) would prove to be a good prognostic indicator for assessment of overall survival and comparable to established nomograms in clear call RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC between 2007 and 2016 were retrospectively identified. The optimal threshold for individual biomarkers among the panel was determined using grid search methodology, receiver operating characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. Prognostic value of CA-ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. ROC and chi-square analyses were performed to compare the predictive ability of CA-ratio to SSIGN, and UISS. Results: Among the 433 clear cell RCC patients treated with nephrectomy, mean age at surgery was 58.4±12, and mean BMI was 30.6±6.8. 158 (36.5%) had CA-ratio < 0.1, while 164 (37.9%) were between 0.1-0.2, and 111 (25.6%) were 0.2+. Pathological T-stage was distributed as follows: T1: 294 (67.9%), T2: 29 (6.7%), T3: 106 (24.5%), and T4: 4 (0.9%). Overall, 60 (13.9%) patients died before end of the follow-up. Area under the curve (AUC) for CA-ratio was 0.72, comparable to SSIGN (AUC 0.73, p = 0.12). On multivariate COX proportional hazards analysis, patients with ratio 0.2 or more were more likely to die compared to patients with ratio < 0.1 [HR:3.45 95%CI:1.68-7.10, p = < 0.001], while adjusting for T-stage, grade, necrosis, and age. Conclusions: CA-ratio is an cost-effective , independent and significant predictor of overall survival in clear cell RCC with accuracy at least as good as other established prognostic tools including SSIGN and UISS. [Table: see text]


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jazmine Arévalo ◽  
David Lorente ◽  
Enrique Trilla ◽  
María Teresa Salcedo ◽  
Juan Morote ◽  
...  

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.


2018 ◽  
Vol 16 (2) ◽  
pp. e297-e305 ◽  
Author(s):  
Antoine Thiery-Vuillemin ◽  
Tiphaine Cholley ◽  
Fabien Calcagno ◽  
Marion Hugues ◽  
Tristan Maurina ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianwei Xing ◽  
Tengyue Zeng ◽  
Shouyong Liu ◽  
Hong Cheng ◽  
Limin Ma ◽  
...  

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.


2019 ◽  
Author(s):  
Yang Qu ◽  
Jiajun Wang ◽  
Qi Bai ◽  
Yangyang Qi ◽  
Yifan Chen ◽  
...  

Abstract Background: Little is known about the associations between PAK1 and anti-tumor immunity in clear-cell renal cell carcinoma (ccRCC). This study aims to explore the prognostic value of PAK1 in ccRCC patients and investigated the molecular immune mechanism for its oncogenic role. Methods: We retrospectively enrolled 282 ccRCC patients undergoing nephrectomy between 2005 and 2007 in Zhongshan hospital. Immunohistochemistry evaluated PAK1, CCL22, FOXP3 and CD8 expression in clinical specimens. Fresh tumor tissues, para-tumor tissues and peripheral blood samples for RT-PCR, ELISA, flow cytometry analyses were collected from patients who underwent nephrectomy in Zhongshan Hospital from September 2017 to April 2018. We compared clinical outcomes by Kaplan-Meier survival analysis and Cox regression model. Bioinformatics analysis performed in TCGA KIRC cohort. Results: High PAK1 expression indicated poorer overall survival (OS) and recurrence free survival (RFS) (both p<0.001) in ccRCC patients. Multivariate analyses indicated PAK1 as an independent prognostic factor. In clinical samples, PAK1 clearly correlated with immunosuppressive microenvironment in ccRCC tissues. Significantly, PAK1 positively correlated with Tumor-infiltrating regulatory T lymphocytes (Tregs). Furthermore, IL-10+ and TGF-β+ tumor-infiltrating Tregs both increased in PAK1 high tumors. Additionally, CCL22 was highly secreted in PAK1 high tumors. After treated by IPA-3 (an PAK1 inhibitor), CCL22 secretion was clearly inhibited (p<0.001). Finally, we built a nomogram to predict overall survival for ccRCC patients with higher predictive accuracy. Conclusions: Increased PAK1 expression predicted dismal prognosis in ccRCC patients by inducing tumor immune escape. IL-10+ and TGF-β+ tumor-infiltrating Tregs recruited by CCL22 play dominant immunosuppressive roles in PAK1 high tumors.


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