摘要
目的探讨维甲酸-干扰素联合应用诱导细胞凋亡相关基因-19(GRIM-19)表达作为结肠直肠癌预后指标的可行性。方法采用免疫组织化学方法检测94例结肠样品中GRIM-19表达情况,通过qRT-PCR方法检测15对结直肠癌组织及临近非肿瘤组织中GRIM-19表达情况,采用秩和检验和Kaplan-Meier生存分析检验GRIM-19表达作为结直肠癌疾病预后的价值。结果 GRIM-19 mRNA和蛋白在腺瘤和临近非肿瘤组织中差异无显著性,然而与正常组织相比,结直肠癌组织中的GRIM-19表达显著抑制(P=0.000)。正常组织中GRIM-19分布于细胞质和细胞核中,而在结直肠癌组织中GRIM-19仅表达在细胞质中。分化不良(P=0.013)、淋巴结转移(P=0.009)、实质器官转移(P=0.045)及血管侵入(P=0.010)的肿瘤GRIM-19显著低表达。经过为期40个月的随访,与GRIM-19阳性患者相比,GRIM-19阴性患者的肿瘤复发率和转移率显著升高(P<0.05),患者的总生存期显著缩短(P<0.01)。结论 GRIM-19表达水平下降的结直肠癌患者往往预后不良,GRIM-19可能作为预测结直肠癌患者预后的新型生物标志物。
Objectiye To discuss the feasibility of retinoic acid - combined with interferon - induced apoptosis related gene - 19（GRIM- 19）as an expression of colorectal cancer prognostic indicators. Methods 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. Results 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 de-pressed in carcinomas compared to matched normal tissues（ P = 0. 000）. Additionally,we found that GRIM - 19 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 = 0. 013）,as well as the presence of lymph nodes （ P = 0. 009）,metastasis to other organs（ P = 0. 045）and vascular invasion（ P = 0. 010）. During a mean period of 40 months follow - up, patients without GRIM - 19 had a statistically significantly lower rate of recurrence/ metastasis（ P 〈 0. 05）and a shorter overall survival time（ P〈 0. 01）than the patients with GRIM - 19 expression. Conclusion GRIM - 19 expression is closely associated with CRC progression and might be a very promising prognostic biomarker for CRC patients.
出处
《临床和实验医学杂志》
2016年第16期1594-1598,共5页
Journal of Clinical and Experimental Medicine
