Gueugnon Fabien, Barascu Aurélia, Mavridis Konstantinos, Petit-Courty Agnès, Marchand-Adam Sylvain, Gissot Valérie, Scorilas Andreas, Guyetant Serge, Courty Yves
INSERM, UMR 1100, F-37032, Tours, France.
Tumour Biol. 2015 Jul;36(7):4979-86. doi: 10.1007/s13277-015-3148-1. Epub 2015 Feb 13.
The KLK13 gene is dysregulated in several carcinomas, and its expression levels seem to be associated with disease prognosis. The aim of our study was to investigate the prognostic potential of KLK13 mRNA expression for patients with nonsmall cell lung cancer (NSCLC). Total RNA was isolated from cancerous and normal tissues from a cohort of 128 NSCLC patients. The KLK13 mRNA transcription levels were measured using a sensitive quantitative RT-PCR method. The results were normalized by dividing the KLK13 mRNA values with the geometric mean of mRNA expression from four reference genes: beta-actin, TATA-binding protein, hypoxanthine phosphoribosyltransferase 1, and acidic ribosomal phosphoprotein P0. The malignant tissues from the majority of patients (59.3 %) contained significantly more KLK13 mRNA transcripts than did the paired nonmalignant tissues (median difference 11.1-fold, P = 0.008). KLK13 was expressed at higher levels in females than that in males (P = 0.021). No other statistically significant association with clinicopathological data was observed. Kaplan-Meier survival analyses demonstrated that patients with KLK13-positive tumors survived significantly longer than those with KLK13-negative ones (P = 0.009). KLK13 expression was also shown to be able to stratify high-risk individuals among patients with early disease stages (P = 0.030). Multivariate Cox regression analysis showed that KLK13 expression is a favorable, independent prognostic indicator of overall survival (OS) (P = 0.024). Our results suggest that KLK13 mRNA expression constitutes a novel biomarker for the prediction of overall survival in NSCLC and that its quantitative assessment in tumor tissues can aid in treatment decision making.
KLK13基因在多种癌症中表达失调，其表达水平似乎与疾病预后相关。我们研究的目的是调查KLK13 mRNA表达对非小细胞肺癌（NSCLC）患者的预后潜力。从128例NSCLC患者队列的癌组织和正常组织中分离总RNA。使用灵敏的定量RT-PCR方法测量KLK13 mRNA转录水平。通过将KLK13 mRNA值除以四个参考基因（β-肌动蛋白、TATA结合蛋白、次黄嘌呤磷酸核糖基转移酶1和酸性核糖体磷蛋白P0）mRNA表达的几何平均值对结果进行标准化。大多数患者（59.3%）的恶性组织中KLK13 mRNA转录本明显多于配对的非恶性组织（中位数差异11.1倍，P = 0.008）。KLK13在女性中的表达水平高于男性（P = 0.021）。未观察到与临床病理数据的其他统计学显著关联。Kaplan-Meier生存分析表明，KLK13阳性肿瘤患者的生存期明显长于KLK13阴性患者（P = 0.009）。KLK13表达还显示能够在疾病早期患者中对高危个体进行分层（P = 0.030）。多变量Cox回归分析表明，KLK13表达是总生存期（OS）的一个有利的独立预后指标（P = 0.024）。我们的结果表明，KLK13 mRNA表达构成了预测NSCLC总生存期的一种新型生物标志物，并且在肿瘤组织中对其进行定量评估有助于治疗决策。
