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高BAX/BCL2 mRNA比值预示着喉鳞状细胞癌的预后良好,尤其是在诊断时淋巴结阴性的患者中。

High BAX/BCL2 mRNA ratio predicts favorable prognosis in laryngeal squamous cell carcinoma, particularly in patients with negative lymph nodes at the time of diagnosis.

作者信息

Giotakis Aris I, Kontos Christos K, Manolopoulos Leonidas D, Sismanis Aristides, Konstadoulakis Manousos M, Scorilas Andreas

机构信息

First Department of Otorhinolaryngology, Athens General Hospital "Hippokration", National and Kapodistrian University of Athens, Athens GR-11527, Greece.

Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens GR-15701, Greece.

出版信息

Clin Biochem. 2016 Aug;49(12):890-6. doi: 10.1016/j.clinbiochem.2016.04.010. Epub 2016 Apr 26.

Abstract

OBJECTIVES

Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. Therefore, accurate prognostic stratification of LSCC patients based on molecular prognostic tumor biomarkers would definitely lead to a better clinical management of this malignancy. The aim of this study was the investigation of the potential combinatorial prognostic value of BCL2 and BAX mRNA expression in LSCC.

DESIGN AND METHODS

Total RNA was isolated from 105 cancerous laryngeal tissue specimens obtained from patients having undergone surgical treatment for primary LSCC. After cDNA preparation, a low-cost, in-house developed, sensitive and accurate real-time quantitative PCR (qPCR) methodology was applied for the quantification of BCL2 and BAX mRNA levels. Then, we carried out a biostatistical analysis to assess the prognostic value of the BAX/BCL2 mRNA expression ratio.

RESULTS

High BAX/BCL2 mRNA expression constitutes a favorable prognosticator in LSCC, predicting significantly longer disease-free survival (P=0.011) and overall survival (P=0.014) of patients. More importantly, the significant prognostic value of the BAX/BCL2 mRNA expression appeared to be independent of the histological grade and size of the malignant laryngeal tumor as well as TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis demonstrated also that the BAX/BCL2 ratio can stratify node-negative (N0) LSCC patients into two subgroups with significantly different DFS and OS (P=0.021 and P=0.009, respectively).

CONCLUSIONS

The BAX/BCL2 mRNA ratio is a putative molecular tissue biomarker in CLL and hence deserves further validation in larger cohorts of LSCC patients.

摘要

目的

喉鳞状细胞癌(LSCC)是头颈部癌症的常见类型,与高转移率和复发率相关。因此,基于分子预后肿瘤生物标志物对LSCC患者进行准确的预后分层肯定会带来对这种恶性肿瘤更好的临床管理。本研究的目的是调查BCL2和BAX mRNA表达在LSCC中的潜在联合预后价值。

设计与方法

从105例接受原发性LSCC手术治疗患者的癌性喉组织标本中分离总RNA。制备cDNA后,应用一种低成本、自行开发、灵敏且准确的实时定量PCR(qPCR)方法来定量BCL2和BAX mRNA水平。然后,我们进行生物统计学分析以评估BAX/BCL2 mRNA表达比值的预后价值。

结果

高BAX/BCL2 mRNA表达是LSCC的一个良好预后指标,可显著预测患者更长的无病生存期(P = 0.011)和总生存期(P = 0.014)。更重要的是,多变量自举Cox回归分析显示,BAX/BCL2 mRNA表达的显著预后价值似乎独立于喉恶性肿瘤的组织学分级、大小以及TNM分期。Kaplan-Meier生存分析还表明,BAX/BCL2比值可将淋巴结阴性(N0)的LSCC患者分为两个无病生存期和总生存期有显著差异的亚组(分别为P = 0.021和P = 0.009)。

结论

BAX/BCL2 mRNA比值是CLL中一种假定的分子组织生物标志物,因此值得在更大规模的LSCC患者队列中进一步验证。

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