How useful is it clinically to analyse the K-ras mutational status for the diagnosis of exocrine pancreatic cancer? A systematic review and meta-analysis

Lucy A. Parker, Blanca Lumbreras, Tomás Lopez, Ildefonso Hernández-Aguado, Miquel Porta

Research output: Contribution to journalReview articleResearchpeer-review

8 Citations (Scopus)

Abstract

Background More clinically meaningful diagnostic tests are needed in exocrine pancreatic cancer (EPC). K-ras mutations are the most frequently acquired genetic alteration in EPC. We analysed the diagnostic utility of detecting K-ras mutations through a systematic analysis of the literature. Methods We searched PubMed using suitable medical subject headings and text words. Original research articles that evaluated the diagnostic accuracy of detecting K-ras mutations for diagnosis of EPC were selected. Two investigators independently extracted data from each study regarding the methodology used, the methodological quality of the study, the diagnostic accuracy reported and the authors' conclusions about clinical applicability of the test. Combined estimates for the sensitivity and specificity of K-ras were determined using bivariate meta-analysis; heterogeneity was explored using meta-regression. Results We assessed 34 studies from 30 published articles. The research reports were prone to numerous methodological biases and often lacked vital information for assessing external validity. The sensitivity of detecting K-ras status ranged from 0% through 100%, and the specificity from 58% through 100%. Diagnostic accuracy was highest when cytohistological samples were used: sensitivity and specificity were 76·5% (66·7-84·2) and 91·8% (87·6-94·1), respectively. Studies conducted in a clinically relevant population observed lower accuracy than case-control designs (68·4% vs. 82·7%). Conclusions Because of the numerous methodological limitations of studies, the utility of analysing K-ras mutations for the diagnosis of EPC remains unknown. Flaws in diagnostic biomarkers with well-established biological properties, as K-ras, become even more relevant when the promises of 'personalized medicine' are pondered. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.
Original languageEnglish
Pages (from-to)793-805
JournalEuropean Journal of Clinical Investigation
Volume41
Issue number7
DOIs
Publication statusPublished - 1 Jul 2011

Keywords

  • Diagnosis/analysis
  • Diagnosis/diagnostic use
  • Diagnosis/methods
  • Epidemiology/diagnosis
  • Genes
  • KRAS oncogene
  • Oncogene protein p21 ras
  • Pancreatic neoplasms/diagnosis
  • Ras
  • Research/methods

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