星形细胞瘤患者癌组织和血清miR-497表达下降及其临床意义

Decreased expression and clinical significance of miR-497in cancer tissues and serum of patients with astrocytoma

目的检测星形细胞瘤患者癌组织和血清中miR-497的表达水平及治疗前后血清miR-497的变化,探讨其作为分子标志物的可能性。方法采集8例星形细胞瘤患者癌组织、4例癌旁组织、3例正常脑组织以及133例治疗前患者的(WHOⅡ级55例、Ⅲ级45例和IV级33例)血清样本,用实时荧光定量RT-PCR法检测miR-497含量,并以80例年龄、性别匹配的健康人作对照。对其中14例患者进行术前、术后血清miR-497含量的比较,ROC曲线分析miR-497对星形细胞瘤的诊断价值。结果miR-497在癌组织中的表达量明显低于癌旁组织和正常脑组织(F=13.78,P<0.05),在患者血清中的浓度也显著降低[(112.69±54.58)fmol/L vs(254.32±142.12)fmol/L,t=10.31,P<0.01]。用于星形细胞瘤诊断的miR-497 ROC曲线下面积(AUCROC)为0.894(95%CI,0.853～0.935),敏感性为82%,特异性为90%。血清miR-497在患者术后明显上升[术后(165.69±56.87)fmol/L vs术前(93.77±38.50)fmol/L,t=3.92,P<0.01]。结论星形细胞瘤患者癌组织和血清miR-497低表达,miR-497有望作为该病诊断及预后评价的检测指标。

Objective To determine the levels of miR-497 in cancer tissues and serum of patients with astrocytoma, analyze the change of serum miR-497 before and after surgical treatment and evaluate the potential of miR-497 as a biomarker of astrocytoma. Methods The cancer tissues from 8 astrocytoma patients, the adjacent non-tumor tissues from 4 astrocytoma patients, the normal tissues from 3 controls, the serum samples from 133 untreated astrocytoma patients （ WHO II grade 55 cases, grade III 33 cases, grade IV 45 cases） and 80 age- and sex-matched healthy individuals were collected to determine the level of miR-497 by quantitative reverse-transcription PCR （ qRT-PCR）, miR-497 levels in the paired serum samples before and after operation from 14 astrocytoma patients were determined to observe the effect of surgical treatment on miRNA. The diagnostic value of miR-497 for astrocytoma was assessed by ROC curve. Re- suits miR-497 expression was significantly lower in cancer tissues than that in adjacent non-tumor tissues （ F = 13.78, P 〈 0.05 ）. Serum miR^97 levels in astrocytoma patients was also significantly lower than that in healthy controls [ （ 112.69 ± 54.58） fmol/L vs （254.32 ± 142.12） fmol/L, t = 10. 31, P 〈0.01 ）. The area under ROC curve （AUCRa） of miR-497 was 0.894 （95% CI, 0. 853 ± 0. 935 ）. The sensitivity was 82% and the specificity was 90%. The serum levels of miR-497 were significantly increased after oper- ation [ postoperative （ 165.69 ± 56.87 ） fmol/L vs preoperative （93.77±38.50） fmol/L, t = 3.92, P 〈 0.01 ]. Conclusion The ex- pression of miR-497 decreased in cancer tissues and serum from astrocytomas patients, so it may be used as noninvasive biomarker for diagnosis and prognosis of astrocytoma.