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

J Surg Oncol. 2017 Aug;116(2):184-194. doi: 10.1002/jso.24648. Epub 2017 May 5.

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.

Keywords: Lauren classification; gastric cancer; miR148a; miR204; miR31; miR375; non-cardial gastric cancer.

Publication types

  • Observational Study

MeSH terms

  • Adenocarcinoma / classification*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • ROC Curve
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sex Factors
  • Stomach Neoplasms / classification*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism

Substances

  • DMAP1 protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Repressor Proteins
  • JAK2 protein, human
  • Janus Kinase 2
  • Protein Serine-Threonine Kinases