GRIM-19 expression is a potent prognostic marker in colorectal cancer

Abstract

Retinoid-interferon-induced mortality-19 (GRIM-19), a recently discovered cell death regulatory gene, may function as a tumor suppressor in many human malignancies. However, the expression of GRIM-19 in and its prognostic value for patients with colorectal cancer (CRC) have not been well investigated to date. Here, GRIM-19 expression was measured immunohistochemically in 94 colon samples and by quantitative real-time reverse transcriptase polymerase chain reaction in 15 paired CRC tissues and adjacent normal tissues. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Our results showed that GRIM-19 mRNA and protein levels in adenoma tissues were similar to those in adjacent normal tissues. However, GRIM-19 expression was severely depressed in carcinomas compared to matched normal tissues (P = .000). Additionally, we found GRIM-19 to be located in both the cytoplasm and nucleus in normal tissues but only in the cytoplasm in CRC tissues. Alteration in GRIM-19 expression occurs early in the pathogenesis of CRC; moreover, low GRIM-19 expression was associated with poor tumor differentiation (P = .013), the presence of lymph nodes (P = .000), metastasis to other organs (P = .045) and vascular invasion (P = .010). During a mean period of 40 months follow-up, patients without GRIM-19 had a statistically significantly lower rate of recurrence/metastasis (P < .05) and a shorter overall survival time (P < .01) than the patients with GRIM-19 expression. Taken together, GRIM-19 expression is closely associated with CRC progression and might be a very promising prognostic biomarker for CRC patients.