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      Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

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          Abstract

          Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma ( P<0.003) or squamous cell carcinoma ( P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort ( P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs.

          Abstract

          Diagnosis of lung cancer through manual histopathology evaluation is insufficient to predict patient survival. Here, the authors use computerized image processing to identify diagnostically relevant image features and use these features to distinguish lung cancer patients with different prognoses.

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          Most cited references39

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          Regularization Paths for Cox's Proportional Hazards Model via Coordinate Descent.

          We introduce a pathwise algorithm for the Cox proportional hazards model, regularized by convex combinations of ℓ1 and ℓ2 penalties (elastic net). Our algorithm fits via cyclical coordinate descent, and employs warm starts to find a solution along a regularization path. We demonstrate the efficacy of our algorithm on real and simulated data sets, and find considerable speedup between our algorithm and competing methods.
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            Global cancer statistics

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              Gene-expression profiles predict survival of patients with lung adenocarcinoma.

              Histopathology is insufficient to predict disease progression and clinical outcome in lung adenocarcinoma. Here we show that gene-expression profiles based on microarray analysis can be used to predict patient survival in early-stage lung adenocarcinomas. Genes most related to survival were identified with univariate Cox analysis. Using either two equivalent but independent training and testing sets, or 'leave-one-out' cross-validation analysis with all tumors, a risk index based on the top 50 genes identified low-risk and high-risk stage I lung adenocarcinomas, which differed significantly with respect to survival. This risk index was then validated using an independent sample of lung adenocarcinomas that predicted high- and low-risk groups. This index included genes not previously associated with survival. The identification of a set of genes that predict survival in early-stage lung adenocarcinoma allows delineation of a high-risk group that may benefit from adjuvant therapy.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                16 August 2016
                2016
                : 7
                : 12474
                Affiliations
                [1 ]Biomedical Informatics Program, Stanford University , 1265 Welch Road, MSOB, X-215, MC 5479, Stanford 94305-5479, California, USA
                [2 ]Department of Genetics, Stanford University , 300 Pasteur Dr, M-344, Stanford 94305-5120, California, USA
                [3 ]Department of Computer Science, Stanford University , 353 Serra Mall, Stanford 94305-9025, California, USA
                [4 ]Department of Pathology, Stanford University , 300 Pasteur Dr, L235, Stanford 94305, California, USA
                Author notes
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-9892-8218
                Article
                ncomms12474
                10.1038/ncomms12474
                4990706
                27527408
                4abe286f-5e6d-44a9-a255-185c10dfced5
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 24 January 2016
                : 06 July 2016
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