Down-regulated miRs specifically correlate with non-cardial gastric cancers and Lauren's classification system

L. Lorenzon, C. Cippitelli, R. Avantifiori, S. Uccini, D. French, M. R. Torrisi, D. Ranieri, P. Mercantini, V. Canu, G. Blandino, M. Cavallini

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Abstract

BACKGROUND AND OBJECTIVES: Gastric cancers are usually characterized using Lauren's classification into intestinal and diffuse types. We previously documented the down-modulation of miR31, miR148a, miR204, and miR375 in gastric cancers. We aimed this manuscript to investigate these miRs with the end-points of diagnosis, Lauren's classification and prognosis. METHODS: A total of 117 resected non-cardial adenocarcinomas were evaluated for miRs' expressions. The performance of miRs' expressions for cancer diagnosis was tested using ROC curves. Logistic regression was conducted with the end-point of Lauren's classification. Kaplan-Meier and Cox analyses were performed for OS, DFS, and DSS. miRs' targets were reviewed using PRISMA method and BCL-2 was further investigated in cell lines. RESULTS: ROC curves documented that miRs' down-modulation was significant in differentiating cancer versus normal tissues. Diffuse type cancers were associated with female sex, young age, and miR375 higher expression. We confirmed BCL-2 as a miR204 target. However, survival analyses confirmed the pathologic criteria (advanced stages, LNR, and low LNH) as the significant variables correlated to worse prognosis. CONCLUSIONS: The down-modulation of miR31, miR148a, miR204, and miR375 is significantly associated with non-cardial gastric cancers and miR375 is specifically linked to Lauren's classification. Nevertheless, standard pathological features display as the independent variables associated with worse prognosis.
Original languageEnglish
Pages (from-to)184-194
Number of pages11
JournalJournal of Surgical Oncology
Volume116
Issue number2
DOIs
Publication statusPublished - Aug 1 2017

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Keywords

  • Adenocarcinoma/classification/genetics/metabolism
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Janus Kinase 2/genetics/metabolism
  • Male
  • MicroRNAs/genetics/metabolism
  • Middle Aged
  • Prognosis
  • Protein-Serine-Threonine Kinases/genetics/metabolism
  • Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
  • ROC Curve
  • Repressor Proteins/genetics/metabolism
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sex Factors
  • Stomach Neoplasms/classification/genetics/metabolism
  • Lauren classification
  • gastric cancer
  • miR148a
  • miR204
  • miR31
  • miR375
  • non-cardial gastric cancer

Cite this

Lorenzon, L., Cippitelli, C., Avantifiori, R., Uccini, S., French, D., Torrisi, M. R., Ranieri, D., Mercantini, P., Canu, V., Blandino, G., & Cavallini, M. (2017). Down-regulated miRs specifically correlate with non-cardial gastric cancers and Lauren's classification system. Journal of Surgical Oncology, 116(2), 184-194. https://doi.org/10.1002/jso.24648 [doi]