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      An improved clear cell renal cell carcinoma stage prediction model based on gene sets

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          Abstract

          Background

          Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and accounts for cancer-related deaths. Survival rates are very low when the tumor is discovered in the late-stage. Thus, developing an efficient strategy to stratify patients by the stage of the cancer and inner mechanisms that drive the development and progression of cancers is critical in early prevention and treatment.

          Results

          In this study, we developed new strategies to extract important gene features and trained machine learning-based classifiers to predict stages of ccRCC samples. The novelty of our approach is that (i) We improved the feature preprocessing procedure by binning and coding, and increased the stability of data and robustness of the classification model. (ii) We proposed a joint gene selection algorithm by combining the Fast-Correlation-Based Filter (FCBF) search with the information value, the linear correlation coefficient, and variance inflation factor, and removed irrelevant/redundant features. Then the logistic regression-based feature selection method was used to determine influencing factors. (iii) Classification models were developed using machine learning algorithms. This method is evaluated on RNA expression value of clear cell renal cell carcinoma derived from The Cancer Genome Atlas (TCGA). The results showed that the result on the testing set (accuracy of 81.15% and AUC 0.86) outperformed state-of-the-art models (accuracy of 72.64% and AUC 0.81) and a gene set FJL-set was developed, which contained 23 genes, far less than 64. Furthermore, a gene function analysis was used to explore molecular mechanisms that might affect cancer development.

          Conclusions

          The results suggested that our model can extract more prognostic information, and is worthy of further investigation and validation in order to understand the progression mechanism.

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          Most cited references16

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          Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism

          Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel KCNJ5 that result in cell depolarization and Ca2+ influx cause ~40% of these tumors 1 . We found five somatic mutations (four altering glycine 403, one altering isoleucine 770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 non-KCNJ5-mutant APAs. These mutations lie in S6 segments that line the channel pore. Both result in channel activation at less depolarized potentials, and glycine 403 mutations also impair channel inactivation. These effects are inferred to cause increased Ca2+ influx, the sufficient stimulus for aldosterone production and cell proliferation in adrenal glomerulosa 2 . Remarkably, we identified de novo mutations at the identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities. These findings implicate gain of function Ca2+ channel mutations in aldosterone-producing adenomas and primary aldosteronism.
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            Multi-institutional validation of a new renal cancer-specific survival nomogram.

            We tested the hypothesis that the prediction of renal cancer-specific survival can be improved if traditional predictor variables are used within a prognostic nomogram. Two cohorts of patients treated with either radical or partial nephrectomy for renal cortical tumors were used: one (n = 2,530) for nomogram development and for internal validation (200 bootstrap resamples), and a second (n = 1,422) for external validation. Cox proportional hazards regression analyses modeled the 2002 TNM stages, tumor size, Fuhrman grade, histologic subtype, local symptoms, age, and sex. The accuracy of the nomogram was compared with an established staging scheme. Cancer-specific mortality was observed in 598 (23.6%) patients, whereas 200 (7.9%) died as a result of other causes. Follow-up ranged from 0.1 to 286 months (median, 38.8 months). External validation of the nomogram at 1, 2, 5, and 10 years after nephrectomy revealed predictive accuracy of 87.8%, 89.2%, 86.7%, and 88.8%, respectively. Conversely, the alternative staging scheme predicting at 2 and 5 years was less accurate, as evidenced by 86.1% (P = .006) and 83.9% (P = .02) estimates. The new nomogram is more contemporary, provides predictions that reach further in time and, compared with its alternative, which predicts at 2 and 5 years, generates 3.1% and 2.8% more accurate predictions, respectively.
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              The changing natural history of renal cell carcinoma.

              Our understanding of the natural history of renal cell carcinoma, the role of nephrectomy, the benefits of immunotherapy and the possibilities of new technologies are evolving and being integrated with advances in classification and staging. We reviewed the relevant literature to clarify these pertinent questions and provide a current review of the changes in the epidemiology, treatment and prognosis of patients with renal cell carcinoma. We comprehensively reviewed the peer reviewed literature on the current management of and results of treatment for renal cell carcinoma. The incidence of and mortality from renal cell carcinoma have continuously increased during the last 50 years. Despite this increase in the number of new patients and consequently the number of deaths yearly the percent of those surviving for 5 years has notably improved. Factors related to improved survival include advances in renal imaging, earlier diagnosis, improved staging, better understanding of prognostic indicators, refinement in surgical technique and the introduction of immunotherapy approaches for advanced disease. Currently patients with localized and metastatic renal cell carcinoma have had improvements in outlook and the therapeutic options available have expanded.
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                Author and article information

                Contributors
                dfyuan@sdu.edu.cn
                tangdq@sdu.edu.cn
                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                8 June 2020
                8 June 2020
                2020
                : 21
                : 232
                Affiliations
                [1 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, School of Information Science and Engineering, , Shandong University, supported by Shandong Provincial Key Laboratory of Wireless Communication Technologies, ; Jinan, 250100 China
                [2 ]GRID grid.452704.0, Center for Gene and Immunothererapy, , The Second Hospital of Shandong University, ; Jinan, 250033 China
                Article
                3543
                10.1186/s12859-020-03543-0
                7278205
                29f2605c-71f0-44ef-af69-819bd9a4d7f3
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 8 November 2019
                : 11 May 2020
                Funding
                Funded by: the Key Research and Development Program of Shandong Province
                Award ID: 2016CYJS01A04
                Award Recipient :
                Funded by: Major Science and Technology Innovation Project of Shandong Province
                Award ID: 2018YFJH0503
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 61671278
                Award ID: 81570407, 81970743
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Bioinformatics & Computational biology
                feature selection,machine learning,clear cell renal cell carcinoma,cancer stage

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