173PD - MicroRNA MIR21, T cells, and PTGS2 expression in Colorectal Cancer

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Gastrointestinal tumours
Topics Colon and Rectal Cancer
Rectal Cancer
Translational Research
Presenter Kosuke Mima
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors K. Mima1, R. Nishihara2, Z.R. Qian2, H. Baba1, S. Ogino3
  • 1Deapartment Of Gastroenterological Surgery, Kumamoto University, 860-8556 - Kumamoto/JP
  • 2Department Of Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 3Division Of Mpe Molecular Pathological Epidemiology, Brigham and Women's Hospital, 02215 - Boston/US



Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to suppresses antitumor T-cell–mediated immunity. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. Thus, we hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on PTGS2 expression and that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue.


Utilizing 765 rectal and colon cancer specimens in the Nurses’ Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse-transcription PCR, and PTGS2 expression by immunohistochemistry. Densities of CD3+, CD8+, CD45RO (PTPRC)+ and FOXP3+ cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Multivariable analyses were conducted to assess the statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis and the association of MIR21 expression with T-cell density, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations.


The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42 to 3.67; Ptrend = 0.0004) but not in PTGS2-absent/low cancers (Ptrend = 0.22; Pinteraction = 0.0004). Tumor MIR21 expression was inversely associated with densities of CD3+ and CD45RO+ cells (Ptrend < 0.0005).


Our data support a possible role of tumor epigenetic deregulation by non-coding RNA in suppressing antitumor T-cell–mediated immune response, and suggest MIR21 as a potential target for immunotherapy and treatment in colorectal cancer.

Clinical trial indentification

Legal entity responsible for the study

USA National Institutes of Health (NIH)


USA National Institutes of Health (NIH)


All authors have declared no conflicts of interest.