Network analysis of histopathological image features and genomics data improving prognosis performance in clear cell renal cell carcinoma.

Introduction: Clear cell renal cell carcinoma is the most common type of kidney cancer, but the prediction of prognosis remains a challenge.

Methods: We collected whole-slide histopathological images, corresponding clinical and genetic information from the The Cancer Imaging Archive and The Cancer Genome Atlas databases and randomly divided patients into training (n = 197) and validation (n = 84) cohorts. After feature extraction by CellProfiler, we used 2 different machine learning techniques (Least Absolute Shrinkage and Selector Operation-regularized Cox and Support Vector Machine-Recursive Feature Elimination) and weighted gene co-expression network analysis to select prognosis-related image features and genes, respectively. These features and genes were integrated into a joint model using random forest and used to create a nomogram that combines other predictive indicators.

Results: A total of 4 overlapped features were identified, represented by the computed histopathological risk score in the random forest model, and showed predictive value for overall survival (test set: 1-year area under the curves (AUC) = 0.726, 3-year AUC = 0.727, and 5-year AUC = 0.764). The histopathological-genetic risk score (HGRS) integrating the genetic information computed performed better than the model that used image features only (test set: 1-year AUC = 0.682, 3-year AUC = 0.734, and 5-year AUC = 0.78). The nomogram (gender, stage, and HGRS) achieved the highest net benefit according to decision curve analysis compared to HGRS or clinical model.

Conclusion: This study developed a histopathological-genetic-related nomogram by combining histopathological features and clinical predictors, providing a more comprehensive prognostic assessment for clear cell renal cell carcinoma patients.