Dataset Information

Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm.

ABSTRACT: It is of great urgency to explore useful prognostic markers and develop a robust prognostic model for patients with clear-cell renal cell carcinoma (ccRCC). Three independent patient cohorts were included in this study. We applied a high-level neural network based on TensorFlow to construct the robust model by using the deep learning algorithm. The deep learning-based model (FB-risk) could perform well in predicting the survival status in the 5-year follow-up, which could also significantly distinguish the patients with high overall survival risk in three independent patient cohorts of ccRCC and a pan-cancer cohort. High FB-risk was found to be partially associated with negative regulation of the immune system. In addition, the novel phenotyping of ccRCC based on the F-box gene family could robustly stratify patients with different survival risks. The different mutation landscapes and immune characteristics were also found among different clusters. Furthermore, the novel phenotyping of ccRCC based on the F-box gene family could perform well in the robust stratification of survival and immune response in ccRCC, which might have potential for application in clinical practices.

SUBMITTER: Chen S

PROVIDER: S-EPMC8860306 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm.

Chen Siteng S Zhang Encheng E Jiang Liren L Wang Tao T Guo Tuanjie T Gao Feng F Zhang Ning N Wang Xiang X Zheng Junhua J

Frontiers in immunology 20220207

It is of great urgency to explore useful prognostic markers and develop a robust prognostic model for patients with clear-cell renal cell carcinoma (ccRCC). Three independent patient cohorts were included in this study. We applied a high-level neural network based on TensorFlow to construct the robust model by using the deep learning algorithm. The deep learning-based model (FB-risk) could perform well in predicting the survival status in the 5-year follow-up, which could also significantly dist ...[more]

PMID: 35197975

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Project description:BackgroundClear-cell renal cell carcinoma (ccRCC) is common and associated with substantial mortality. TNM stage and histopathological grading have been the sole determinants of a patient's prognosis for decades and there are few prognostic biomarkers used in clinical routine. Management of ccRCC involves multiple disciplines such as urology, radiology, oncology, and pathology and each of these specialties generates highly complex medical data. Here, artificial intelligence (AI) could prove extremely powerful to extract meaningful information to benefit patients.ObjectiveIn the study, we developed and evaluated a multimodal deep learning model (MMDLM) for prognosis prediction in ccRCC.Design setting and participantsTwo mixed cohorts of non-metastatic and metastatic ccRCC patients were used: (1) The Cancer Genome Atlas cohort including 230 patients and (2) the Mainz cohort including 18 patients with ccRCC. For each of these patients, we trained the MMDLM on multiscale histopathological images, CT/MRI scans, and genomic data from whole exome sequencing.Outcome measurements and statistical analysisOutcome measurements included Harrell's concordance index (C-index) and also various performance parameters for predicting the 5-year survival status (5YSS). Different visualization techniques were used to make our model more transparent.ResultsThe MMDLM showed great performance in predicting the prognosis of ccRCC patients with a mean C-index of 0.7791 and a mean accuracy of 83.43%. Training on a combination of data from different sources yielded significantly better results compared to when only one source was used. Furthermore, the MMDLM's prediction was an independent prognostic factor outperforming other clinical parameters.InterpretationMultimodal deep learning can contribute to prognosis prediction in ccRCC and potentially help to improve the clinical management of this disease.Patient summaryAn AI-based computer program can analyze various medical data (microscopic images, CT/MRI scans, and genomic data) simultaneously and thereby predict the survival time of patients with renal cancer.

Project description:As the most common type of renal cell carcinoma (RCC), the renal clear cell carcinoma (ccRCC) is highly malignant and insensitive to chemotherapy or radiotherapy. Although systemic immunotherapies have been successfully applied to ccRCC in recent years, screening for patients who can benefit most from these therapies is still essential and challenging due to immunological heterogeneity of ccRCC patients. To this end, we implemented a series of deep investigation on the expression and clinic data of ccRCC from The Cancer Genome Atlas (TCGA) International Consortium for Cancer Genomics (ICGC). We identified a total of 946 immune-related genes that were differentially expressed. Among them, five independent genes, including SHC1, WNT5A, NRP1, TGFA, and IL4R, were significantly associated with survival and used to construct the immune-related prognostic differential gene signature (IRPDGs). Then the ccRCC patients were categorized into high-risk and low-risk subgroups based on the median risk score of the IRPDGs. IRPDGs subgroups displays distinct genomic and immunological characteristics. Known immunotherapy-related genes show different mutation burden, wherein the mutation rate of VHL was higher than 40% in the two IRPDGs subgroups, and SETD2 and BAP1 mutations differed most between two groups with higher frequency in the high-risk subgroup. Moreover, IRPDGs subgroups had different abundance in tumor-infiltrating immune cells (TIICs) with distinct immunotherapy efficacy. Plasma cells, regulatory cells (Tregs), follicular helper T cells (Tfh), and M0 macrophages were enriched in the high-risk group with a higher tumor immune dysfunction and rejection (TIDE) score. In contrast, the low-risk group had abundant M1 macrophages, mast cell resting and dendritic cell resting infiltrates with lower TIDE score and benefited more from immune checkpoint inhibitors (ICI) treatment. Compared with other biomarkers, such as TIDE and tumor inflammatory signatures (TIS), IRPDGs demonstrated to be a better biomarker for assessing the prognosis of ccRCC and the efficacy of ICI treatment with the promise in screening precise patients for specific immunotherapies.

Dataset Information

Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm.

Publications

Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm.

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