Stromal miR-21 is more important than miR-21 of tumour cells for the progression of gastric cancer

Histopathology. 2014 Dec;65(6):775-83. doi: 10.1111/his.12491. Epub 2014 Sep 2.

Abstract

Background: Gastric cancer (GC) is a common cancer globally. miRNA-21 (miR-21) appears to be important in the tumourigenesis of almost all types of human cancer. However its precise localization in GC has yet to be clarified. We thus examined miR-21 localization in GC and revealed its clinicopathological importance.

Methods: Tissue arrays of 469 GCs from 454 patients were examined for miR-21 using in situ hybridization (ISH). The positivity was evaluated separately in tumour cells and stromal cells. Conventional sections of 10 GCs were also stained. Eight cases were examined by quantitative RT-PCR (qRT-PCR).

Results: miR-21 was highly expressed in tumour cells of 44% of cases and in cancer stroma of 51% of cases. miR-21 of tumour cells was not related to clinicopathological factors, whereas stromal miR-21 was related to many factors including tumour stage, size, and nodal metastasis. Stromal miR-21 gradually increased during tumour progression. ISH of whole sections showed stronger stromal positivity in invasive areas with desmoplastic reaction. Cancer stroma also showed higher miR-21 expression than tumour and non-tumourous tissue in the qRT-PCR study.

Conclusion: Stromal miR-21 is closely related to tumour progression in GC. Stromal miR-21 of tumours might be a target of treatment.

Keywords: cancer stroma; cancer-associated fibroblast; gastric cancer; in-situ hybridization; miR-21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression
  • Female
  • Humans
  • In Situ Hybridization
  • Male
  • MicroRNAs / analysis
  • MicroRNAs / genetics*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Tissue Array Analysis
  • Tumor Microenvironment / genetics*

Substances

  • MIRN21 microRNA, human
  • MicroRNAs