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An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma.

ABSTRACT: Objective: The International Society of Urological Pathology (ISUP) has proposed a grading system to classify renal cell carcinoma (RCC). However, classification using biopsy specimens remains problematic and, consequently, the accuracy of a biopsy-based diagnosis is relatively poor. This study aims to combine clinical and immunohistochemical (IHC) factors for the prediction of high ISUP grade clear cell RCC (ccRCC) in an attempt to complement and improve the accuracy of a biopsy-based diagnosis. Methods: A total of 362 ccRCC patients were enrolled in this study and used for the training set. We performed IHC analysis of 18 protein markers on standard tissue sections using an automated stainer. Multivariate logistic regression models were developed to evaluate independent predictors for high ISUP grade. We evaluated different prediction models using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) analysis. A nomogram for the derivation of an integrated score for predicting high ISUP grade ccRCC and a calibration curve were also plotted. Finally, an internal validation cohort was examined to evaluate the performance of our integrated scoring system and nomogram. Results: Multivariate logistic analyses revealed seven credible candidates for predicting high grade ISUP. These were age, tumor diameter, surgery, and CK7, Ki-67, PTEN, and MTOR protein expression. The ROC curves for the clinical, IHC and integrated models were compared in the training set, and the AUC for each was 0.731, 0.744, and 0.801, respectively. DeLong's test showed that the integrated model was significantly better at predicting high ISUP grade, when compared with the other models. Internal validation confirmed the good performance of the integrated score in predicting ISUP grade. Conclusion: We have developed a nomogram integrating clinical and immunohistochemical parameters to predict high ISUP grade for M0 ccRCC patients. This nomogram may offer potentially useful information during preoperative individualized patient risk assessment, and consequently may help urologists when planning personalized management regimens.

SUBMITTER: Wu J

PROVIDER: S-EPMC6305456 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma.

Wu Junlong J Xu Wen-Hao WH Wei Yu Y Qu Yuan-Yuan YY Zhang Hai-Liang HL Ye Ding-Wei DW

Frontiers in oncology 20181218

<b>Objective:</b> The International Society of Urological Pathology (ISUP) has proposed a grading system to classify renal cell carcinoma (RCC). However, classification using biopsy specimens remains problematic and, consequently, the accuracy of a biopsy-based diagnosis is relatively poor. This study aims to combine clinical and immunohistochemical (IHC) factors for the prediction of high ISUP grade clear cell RCC (ccRCC) in an attempt to complement and improve the accuracy of a biopsy-based di ...[more]

PMID: 30619768

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Project description:ObjectiveThis study aims to develop and validate a CT-based radiomics nomogram integrated with clinic-radiological factors for preoperatively differentiating high-grade from low-grade clear cell renal cell carcinomas (CCRCCs).Methods370 patients with complete clinical, pathological, and CT image data were enrolled in this retrospective study, and were randomly divided into training and testing sets with a 7:3 ratio. Radiomics features were extracted from nephrographic phase (NP) contrast-enhanced images, and then a radiomics model was constructed by the selected radiomics features using a multivariable logistic regression combined with the most suitable feature selection algorithm determined by the comparison among least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE) and ReliefF. A clinical model was established using clinical and radiological features. A radiomics nomogram was constructed by integrating the radiomics signature and independent clinic-radiological features. Performance of these three models was assessed using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).ResultsUsing multivariate logistic regression analysis, three clinic-radiological features including intratumoral necrosis (OR=3.00, 95% CI=1.30-6.90, p=0.049), intratumoral angiogenesis (OR=3.28, 95% CI=1.22-8.78, p=0.018), and perinephric metastasis (OR=2.90, 95% CI=1.03-8.17, p=0.044) were found to be independent predictors of WHO/ISUP grade in CCRCC. Incorporating the above clinic-radiological predictors and radiomics signature constructed by LASSO, a CT-based radiomics nomogram was developed, and presented better predictive performance than clinic-radiological model and radiomics signature model, with an AUC of 0.891 (95% CI=0.832-0.962) and 0.843 (95% CI=0.718-0.975) in the training and testing sets, respectively. DCA indicated that the nomogram has potential clinical usefulness.ConclusionThe CT-based radiomics nomogram is a promising tool to predict WHO/ISUP grade of CCRCC preoperatively and noninvasively.

Project description:Long non-coding RNAs (lncRNAs) which have little or no protein-coding capacity, due to their potential roles in the cancer disease, caught a particular interest. Our study aims to develop an lncRNAs-based classifier and a nomogram incorporating the lncRNAs classifier and clinicopathologic factors to help to improve the accuracy of recurrence prediction for head and neck squamous cell carcinoma (HNSCC) patients. The HNSCC lncRNAs profiling data and the corresponding clinicopathologic information were downloaded from TANRIC database and cBioPortal. Using univariable Cox regression and Least absolute shrinkage and selection operator (LASSO) analysis, we developed 15-lncRNAs-based classifier related to recurrence. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to evaluate clinical value of our nomogram. Consequently, fifteen recurrence-free survival (RFS) -related lncRNAs were identified, and the classifier consisting of the established 15 lncRNAs could effectively divide patients into high-risk and low-risk subgroup. The prediction ability of the 15-lncRNAs-based classifier for predicting 3- year and 5-year RFS were 0.833 and 0.771. Independent factors derived from multivariable analysis to predict recurrence were number of positive LNs, margin status, mutation count and lncRNAs classifier, which were all embedded into the nomogram. The calibration curve for the recurrence probability showed that the predictions based on the nomogram were in good coincide with practical observations. The C-index of the nomogram was 0.76 (0.72-0.79), and the area under curve (AUC) of nomogram in predicting RFS was 0.809, which were significantly higher than traditional TNM stage and 15-lncRNAs-based classifier. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage and 15-lncRNAs-based classifier. The results were confirmed externally. In summary, a visually inclusive nomogram for patients with HNSCC, comprising genomic and clinicopathologic variables, generates more accurate prediction of the recurrence probability when compared TNM stage alone, but more additional data remains needed before being used in clinical practice.

Project description:Prostate cancer is a highly heterogeneous disease; therefore, estimating patient prognosis accurately is challenging due to the lack of biomarkers with sufficient specificity and sensitivity. One of the current challenges lies in integrating genomic and transcriptomic data with clinico-pathological features and in incorporating their application in everyday clinical practice. Therefore, we aimed to model a risk score and nomogram containing long non-coding RNA (lncRNA) expression and clinico-pathological data to better predict the probability of prostate cancer progression. We performed bioinformatics analyses to identify lncRNAs differentially expressed across various prostate cancer stages and associated with progression-free survival. This information was further integrated into a prognostic risk score and nomogram containing transcriptomic and clinico-pathological features to estimate the risk of disease progression. We used RNA-seq data from 5 datasets from public repositories (total n = 178) comprising different stages of prostate cancer: pre-treatment primary prostate adenocarcinomas, post-treatment tumors and metastatic castration resistant prostate cancer. We found 30 lncRNAs with consistent differential expression in all comparisons made using two R-based packages. Multivariate progression-free survival analysis including the ISUP group as covariate, revealed that 7/30 lncRNAs were significantly associated with time-to-progression. Next, we combined the expression of these 7 lncRNAs into a multi-lncRNA score and dichotomized the patients into low- or high-score. Patients with a high-score showed a 4-fold risk of disease progression (HR = 4.30, 95 %CI = 2.66-6.97, p = 3.1e-9). Furthermore, we modelled a combined risk-score containing information on the multi-lncRNA score and ISUP group. We found that patients with a high-risk score had nearly 8-fold risk of progression (HR = 7.65, 95 %CI = 4.05-14.44, p = 3.4e-10). Finally, we created and validated a nomogram to help uro-oncologists to better predict patient's risk of progression at 3- and 5-years post-diagnosis. In conclusion, the integration of lncRNA expression data and clinico-pathological features of prostate tumors into predictive models might aid in tailored disease risk assessment and treatment for patients with prostate cancer.

Project description:The tumor stage, size, grade, and necrosis (SSIGN) score was originally defined using patients treated with radical nephrectomy (RN) between 1970 and 1998 for clear cell renal cell carcinoma (ccRCC), excluding patients treated with partial nephrectomy (PN).To characterize the original SSIGN score cohort with longer follow-up and evaluate a contemporary series of patients treated with RN and PN.Retrospective single-institution review of 3600 consecutive surgically treated ccRCC patients grouped into three cohorts: original RN, contemporary (1999-2010) RN, and contemporary PN.RN or PN.The association of the SSIGN score with risk of death from RCC was assessed using a Cox proportional hazards regression model, and predictive ability was summarized with a C-index.The SSIGN scores differed significantly between the original RN, contemporary RN, and contemporary PN cohorts (p<0.001), with SSIGN ?4 in 53.5%, 62.7%, and 4.7%, respectively (p<0.001). The median durations of follow-up for these groups were 20.1, 9.2, and 7.6 yr, respectively. Each increase in the SSIGN score was predictive of death from RCC (hazard ratios [HRs]: 1.41 for original RN, 1.37 for contemporary RN, and 1.70 for contemporary PN; all p<0.001). The C-indexes for these models were 0.82, 0.84, and 0.82 for original RN, contemporary RN, and contemporary PN, respectively. After accounting for an era-specific improvement in survival among RN patients (HR: 0.53 for contemporary vs original RN; p<0.001), the SSIGN score remained predictive of death from RCC (HR: 1.40; p<0.001).The SSIGN score remains a useful prediction tool for patients undergoing RN with 20-yr follow-up. When applied to contemporary RN and PN patients, the score retained strong predictive ability. These results should assist in patient counseling and help guide surveillance for ccRCC patients treated with RN or PN.We evaluated the validity of a previously described tool to predict survival following surgery in contemporary patients with kidney cancer. We found that this tool remains valid even when extended to patients significantly different than were initially used to create the tool.

Dataset Information

An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma.

Publications

An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma.

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