Hao Miao, Shu Zhenbo, Sun Hongyan, Sun Ran, Wang Yuqian, Liu Tie, Ji Degang, Cong Xianling
Science Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Department of Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Hum Pathol. 2015 Dec;46(12):1815-20. doi: 10.1016/j.humpath.2015.07.020. Epub 2015 Aug 4.
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.
维甲酸-干扰素诱导死亡率19(GRIM-19)是最近发现的一种细胞死亡调节基因,可能在多种人类恶性肿瘤中发挥肿瘤抑制作用。然而,迄今为止,GRIM-19在结直肠癌(CRC)患者中的表达及其预后价值尚未得到充分研究。在此,通过免疫组织化学方法检测了94例结肠样本中GRIM-19的表达,并通过定量实时逆转录聚合酶链反应检测了15对CRC组织及其相邻正常组织中GRIM-19的表达。使用Kaplan-Meier生存估计和对数秩检验评估预后意义。我们的结果表明,腺瘤组织中GRIM-19的mRNA和蛋白质水平与相邻正常组织中的相似。然而,与匹配的正常组织相比,癌组织中GRIM-19的表达严重下调(P = 0.000)。此外,我们发现GRIM-19在正常组织的细胞质和细胞核中均有定位,但在CRC组织中仅存在于细胞质中。GRIM-19表达的改变在CRC发病机制的早期就已出现;此外,低GRIM-19表达与肿瘤分化差(P = 0.013)、淋巴结转移(P = 0.000)、其他器官转移(P = 0.045)和血管侵犯(P = 0.010)相关。在平均40个月的随访期内,未表达GRIM-19的患者复发/转移率在统计学上显著低于表达GRIM-19的患者(P < 0.05),总生存时间也较短(P < 0.01)。综上所述,GRIM-19表达与CRC进展密切相关,可能是CRC患者非常有前景的预后生物标志物。