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存活素mRNA在胆囊癌中的表达:一种诊断和预后标志物?

Expression of survivin mRNA in gallbladder cancer: a diagnostic and prognostic marker?

作者信息

Nigam Jaya, Chandra Abhijit, Kazmi Hasan Raza, Parmar Devendra, Singh Devendra, Gupta Vishal, M Noushif

机构信息

Department of Surgical Gastroenterology, King George's Medical University, Lucknow, Uttar Pradesh, 226003, India.

出版信息

Tumour Biol. 2014 Sep;35(9):9241-6. doi: 10.1007/s13277-014-2200-x. Epub 2014 Jun 17.

Abstract

Survivin, an inhibitor of apoptosis, has been shown to be expressed in various malignancies. However, its role in gallbladder cancer (GBC) has not been evaluated yet. We investigated its expression in peripheral blood of patients with gallbladder diseases (gallstone disease (GSD), n = 30; GBC, n = 39) and compared with healthy controls (n = 25). Survivin expression was correlated with clinicopathological parameters, diagnosis, and prognosis of patients with GBC. Expression of survivin messenger RNA (mRNA) in blood was evaluated by real-time PCR. Significantly higher (P < 0.0001) expression of survivin mRNA was observed in GBC (2.2-fold) and GSD (1.52-fold) as compared to control. In GBC, increased survivin expression was significantly associated with higher tumor stage (stage III vs. stage II; P < 0.0001) and tumor differentiation (poor and moderate vs. well differentiated; P < 0.0001). No significant correlation was observed with any of the other clinicopathological parameters (age, gender, and presence or absence of gallstones) studied. Cutoff value of survivin mRNA relative quantification (RQ) was 1.08, with a sensitivity of 98.55 % and specificity of 100 % for the diseased group (GSD or GBC). RQ value of 1.71 differentiated GBC from GSD with a sensitivity of 89.74 % and specificity of 100 %. Increased expression of survivin was associated with a shorter median overall survival (12 vs. 18 months) in GBC patients. Differential expression of survivin in GBC suggests its possible role and association with poor prognosis. Expression of survivin in peripheral blood could be useful both in the diagnosis and prognosis of GBC.

摘要

存活素是一种凋亡抑制因子,已证实在多种恶性肿瘤中均有表达。然而,其在胆囊癌(GBC)中的作用尚未得到评估。我们研究了其在胆囊疾病患者(胆结石病(GSD),n = 30;GBC,n = 39)外周血中的表达情况,并与健康对照者(n = 25)进行比较。存活素的表达与GBC患者的临床病理参数、诊断及预后相关。通过实时定量聚合酶链反应(PCR)评估血液中存活素信使核糖核酸(mRNA)的表达。与对照组相比,GBC组(2.2倍)和GSD组(1.52倍)存活素mRNA的表达显著升高(P < 0.0001)。在GBC中,存活素表达增加与更高的肿瘤分期(III期 vs. II期;P < 0.0001)和肿瘤分化程度(低分化和中分化 vs. 高分化;P < 0.0001)显著相关。在所研究的其他临床病理参数(年龄、性别、有无胆结石)中未观察到显著相关性。存活素mRNA相对定量(RQ)的截断值为1.08,对疾病组(GSD或GBC)的敏感性为98.55%,特异性为100%。RQ值为1.71时可区分GBC和GSD,敏感性为89.74%,特异性为100%。存活素表达增加与GBC患者较短的中位总生存期(12个月 vs. 18个月)相关。GBC中存活素的差异表达提示其可能发挥的作用以及与不良预后的关联。外周血中存活素的表达在GBC的诊断和预后评估中均可能具有应用价值。

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