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The first competing risk survival nomogram in patients with papillary renal cell carcinoma.

ABSTRACT: There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUC_t of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.

SUBMITTER: Su X

PROVIDER: S-EPMC8178392 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPapillary renal cell carcinoma (pRCC) is the largest histologic subtype of non-clear-cell RCC. To date, there is no reliable nomogram to predict the prognosis of patients with pRCC after nephrectomy. We aimed to first establish an effective nomogram to predict the overall survival (OS) of patients with pRCC after nephrectomy.MethodsA total of 3,528 eligible patients with pRCC after nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The patients were randomized into the training cohort (n = 2,472) and the validation cohort (n = 1,056) at a 7:3 ratio. In total, 122 real-world samples from our institute (titled the AHMU-pRCC cohort) were used as the external validation cohort. Univariate and subsequent multivariate Cox regression analyses were conducted to identify OS-related prognostic factors, which were further used to establish a prognostic nomogram for predicting 1-, 3-, and 5-year OS probabilities. The performance of the nomogram was evaluated by using the concordance index (C-index), receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA).ResultsMultivariate Cox analysis showed that age, race, marital status, TNM stage, tumor size, and surgery were significant OS-related prognostic factors. A prognostic model consisting of these clinical parameters was developed and virtualized by a nomogram. High C-index and area under the ROC curve (AUC) values of the nomogram at 1, 3, and 5 years were found in the training, validation, and AHMU-pRCC cohorts. The calibration plot and DCA also showed that the nomogram had a satisfactory clinical application value. A risk classification system was established to risk-stratify patients with pRCC.ConclusionBased on a large cohort from the public SEER database, a reliable nomogram predicting the OS of patients with pRCC after nephrectomy was constructed, which could optimize the survival assessment and clinical treatment.

Project description:Background: Papillary renal cell carcinoma (PRCC) accounts for 15% of all renal cell carcinomas. The molecular mechanisms of renal papillary cell carcinoma remain unclear, and treatments for advanced disease are limited.Result: We built the computing model as follows: Risk score = 1.806 * TPX2 - 0.355 * TXNRD2 - 0.805 * SLC6A20. The 3-year AUC of overall survival was 0.917 in the training set (147 PRCC samples) and 0.760 in the test set (142 PRCC samples). Based on the robust model, M2 macrophages showed positive correlation with risk score, while M1 macrophages were the opposite. PRCC patients with low risk score showed higher tumor mutation burden. TPX2 is a risk factor, and co-expression factors were enriched in cell proliferation and cancer-related pathways. Finally, the proliferation and invasion of PRCC cell line were decreased in the TPX2 reduced group, and the differential expression was identified. TPX2 is a potential risk biomarker which involved in cell proliferation in PRCC.Conclusion: We conducted a study to develop a three gene model for predicting prognosis in patients with papillary renal cell carcinoma. Our findings may provide candidate biomarkers for prognosis that have important implications for understanding the therapeutic targets of papillary renal cell carcinoma.Method: Gene expression matrix and clinical data were obtained from TCGA (The Cancer Genome Atlas), GSE26574, GSE2048, and GSE7023. Prognostic factors were identified using "survival" and "rbsurv" packages, and a risk score was constructed using Multivariate Cox regression analysis. The co-expression networks of the factors in model were constructed using the "WGCNA" package. The co-expression genes of factors were enriched and displayed the biological process. Based on this robust risk model, immune cells infiltration proportions and tumor mutation burdens were compared between risk groups. Subsequently, using the PRCC cell line, the role of TPX2 was determined by Cell proliferation assay, 5-Ethynyl-20-deoxyuridine assay and Transwell assay.

Project description:BackgroundRenal cell carcinoma (RCC) is a common malignant tumor in the elderly, with an increasing trend in recent years. We aimed to construct a nomogram of cancer-specific survival (CSS) and overall survival (OS) in elderly patients with nonmetastatic renal cell carcinoma (nmRCC).MethodsClinicopathological information was downloaded from the Surveillance, Epidemiology, and End Results (SEER) program in elderly patients with nmRCC from 2010 to 2015. All patients were randomly assigned to a training cohort (70%) or a validation cohort (30%). Univariate and multivariate Cox regression analyses were used to identify independent risk factors for patient outcomes in the training cohort. A nomogram was constructed based on these independent risk factors to predict the 1-, 3-, and 5-year CSS and OS in elderly patients with nmRCC. We used a range of methods to validate the accuracy and reliability of the model, including the calibration curve, consistency index (C-index), and the area under the receiver operating curve (AUC). Decision curve analysis (DCA) was used to test the clinical utility of the model.ResultsA total of 12,116 patients were enrolled in the study. Patients were randomly assigned to the training cohort (N = 8,514) and validation cohort (N = 3,602). In the training cohort, univariate and multivariate Cox regression analysis showed that age, marriage, tumor histological type, histological tumor grade, TN stage, tumor size, and surgery are independent risk factors for prognosis. A nomogram was constructed based on independent risk factors to predict CSS and OS at 1-, 3-, and 5- years in elderly patients with nmRCC. The C-index of the training and validation cohorts in CSS were 0.826 and 0.831; in OS, they were 0.733 and 0.734, respectively. The AUC results of the training and validation cohort were similar to the C-index. The calibration curve indicated that the observed value is highly consistent with the predicted value, meaning the model has good accuracy. DCA results suggest that the clinical significance of the nomogram is better than that of traditional TNM staging.ConclusionsWe built a nomogram prediction model to predict the 1-, 3- and 5-year CSS and OS of elderly nmRCC patients. This model has good accuracy and discrimination and can help doctors and patients make clinical decisions and active monitoring.

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The first competing risk survival nomogram in patients with papillary renal cell carcinoma.

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