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

• Published in: Human pathology Vol. 46; no. 12; pp. 1815 - 1820
• Main Authors: Hao, Miao, PhD, Shu, Zhenbo, MD, Sun, Hongyan, MD, Sun, Ran, MD, Wang, Yuqian, PhD, Liu, Tie, MD, Ji, Degang, MD, Cong, Xianling, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2015; Elsevier Limited
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Aged; Antigens; Apoptosis; Apoptosis Regulatory Proteins - analysis; Apoptosis Regulatory Proteins - biosynthesis; Biomarkers, Tumor - analysis; Breast cancer; Cancer therapies; Colorectal cancer; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Cytoplasm; Female; Gene expression; GRIM-19; Hospitals; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Liver cancer; Lymphatic system; Male; Medical prognosis; Metastasis; Middle Aged; Mortality; NADH, NADPH Oxidoreductases - analysis; NADH, NADPH Oxidoreductases - biosynthesis; Pathology; Prognosis; Prognostic biomarker; Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Tumor suppressor; Tumors; China; Immunohistochemistry; Tumor suppressor; GRIM-19; Colorectal cancer; Prognostic biomarker
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2015.07.020

Summary 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.