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LUADpp: an effective prediction model on prognosis of lung adenocarcinomas based on somatic mutational features.

ABSTRACT: BACKGROUND:Lung adenocarcinoma is the most common type of lung cancers. Whole-genome sequencing studies disclosed the genomic landscape of lung adenocarcinomas. however, it remains unclear if the genetic alternations could guide prognosis prediction. Effective genetic markers and their based prediction models are also at a lack for prognosis evaluation. METHODS:We obtained the somatic mutation data and clinical data for 371 lung adenocarcinoma cases from The Cancer Genome Atlas. The cases were classified into two prognostic groups (3-year survival), and a comparison was performed between the groups for the somatic mutation frequencies of genes, followed by development of computational models to discrete the different prognosis. RESULTS:Genes were found with higher mutation rates in good (? 3-year survival) than in poor (

SUBMITTER: Yu J

PROVIDER: S-EPMC6431052 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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LUADpp: an effective prediction model on prognosis of lung adenocarcinomas based on somatic mutational features.

Yu Jiaxian J Hu Yueming Y Xu Yafei Y Wang Jue J Kuang Jiajie J Zhang Wei W Shao Jianlin J Guo Dianjing D Wang Yejun Y

BMC cancer 20190322 1

<h4>Background</h4>Lung adenocarcinoma is the most common type of lung cancers. Whole-genome sequencing studies disclosed the genomic landscape of lung adenocarcinomas. however, it remains unclear if the genetic alternations could guide prognosis prediction. Effective genetic markers and their based prediction models are also at a lack for prognosis evaluation.<h4>Methods</h4>We obtained the somatic mutation data and clinical data for 371 lung adenocarcinoma cases from The Cancer Genome Atlas. T ...[more]

PMID: 30902072

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Project description:BackgroundAfter curative surgical resection, about 30-75% lung adenocarcinoma (LUAD) patients suffer from recurrence with dismal survival outcomes. Identification of patients with high risk of recurrence to impose intense therapy is urgently needed.Materials and methodsGene expression data of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were calculated by comparing the recurrent and primary tissues. Prognostic genes associated with the recurrence-free survival (RFS) of LUAD patients were identified using univariate analysis. LASSO Cox regression and multivariate Cox analysis were applied to extract key genes and establish the prediction model.ResultsWe detected 37 DEGs between primary and recurrent LUAD tumors. Using univariate analysis, 31 DEGs were found to be significantly associated with RFS. We established the RFS prediction model including thirteen genes using the LASSO Cox regression. In the training cohort, we classified patients into high- and low-risk groups and found that patients in the high-risk group suffered from worse RFS compared to those in the low-risk group (P < 0.01). Concordant results were confirmed in the internal and external validation cohort. The efficiency of the prediction model was also confirmed under different clinical subgroups. The high-risk group was significantly identified as the risk factor of recurrence in LUAD by the multivariate Cox analysis (HR = 13.37, P = 0.01). Compared to clinicopathological features, our prediction model possessed higher accuracy to identify patients with high risk of recurrence (AUC = 96.3%). Finally, we found that the G2M checkpoint pathway was enriched both in recurrent tumors and primary tumors of high-risk patients.ConclusionsOur recurrence-specific gene-based prognostic prediction model provides extra information about the risk of recurrence in LUAD, which is conducive for clinicians to conduct individualized therapy in clinic.

Project description:What motivates an action in the absence of a definite reward? Taking the case of visuomotor control, we consider a minimal control problem that is how select the next saccade, in a sequence of discrete eye movements, when the final objective is to better interpret the current visual scene. The visual scene is modeled here as a partially-observed environment, with a generative model explaining how the visual data is shaped by action. This allows to interpret different action selection metrics proposed in the literature, including the Salience, the Infomax and the Variational Free Energy, under a single information theoretic construct, namely the view-based Information Gain. Pursuing this analytic track, two original action selection metrics named the Information Gain Lower Bound (IGLB) and the Information Gain Upper Bound (IGUB) are then proposed. Showing either a conservative or an optimistic bias regarding the Information Gain, they strongly simplify its calculation. An original fovea-based visual scene decoding setup is then proposed, with numerical experiments highlighting different facets of artificial fovea-based vision. A first and principal result is that state-of-the-art recognition rates are obtained with fovea-based saccadic exploration, using less than 10% of the original image's data. Those satisfactory results illustrate the advantage of mixing predictive control with accurate state-of-the-art predictors, namely a deep neural network. A second result is the sub-optimality of some classical action-selection metrics widely used in the literature, that is not manifest with finely-tuned inference models, but becomes patent when coarse or faulty models are used. Last, a computationally-effective predictive model is developed using the IGLB objective, with pre-processed visual scan-path read-out from memory, bypassing computationally-demanding predictive calculations. This last simplified setting is shown effective in our case, showing both a competing accuracy and a good robustness to model flaws.

Dataset Information

LUADpp: an effective prediction model on prognosis of lung adenocarcinomas based on somatic mutational features.

Publications

LUADpp: an effective prediction model on prognosis of lung adenocarcinomas based on somatic mutational features.

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