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PLoS One. 2018 Apr 4;13(4):e0194844. doi: 10.1371/journal.pone.0194844. eCollection 2018.

Integrative multi-platform meta-analysis of gene expression profiles in pancreatic ductal adenocarcinoma patients for identifying novel diagnostic biomarkers.

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Department of Medical Oncology, Virgen de la Salud Hospital, Toledo, Spain.
Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain.
Department of Medical Oncology, Virgen de la Victoria Hospital, Malaga, Spain.
Department of Health Sciences, University of Jaen, Jaen, Spain.
Department of Medical Oncology, University General Hospital of Elche, Alicante, Spain.
Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada, Spain.
Department of Medical Oncology, Hospital Ramón y Cajal Hospital, Madrid, Spain.
Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofia Hospital, University of Cordoba, Cordoba, Spain.
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Granada, Spain.


Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses ('gained' genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease.

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