mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients
mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients
复制标题
DOI：
10.1515/cclm-2015-0456
复制
发表时间：
2016-02-01
影响因子：
6.8
通讯作者：
Scorilas, Andreas
中科院分区：
文献类型：
--
作者：
Kontos, Christos K.;Adamopoulos, Panagiotis G.;Scorilas, Andreas
背景：组织激肽释放酶和激肽释放酶相关肽酶（KLK）组成丝氨酸内肽酶家族，在肿瘤学中具有很大的临床意义，因为它们作为几种人类恶性肿瘤的诊断和/或预后分子生物标志物的潜力已经得到证实。然而，该家族的任何成员都没有在血液恶性肿瘤方面进行过研究。基于我们对慢性淋巴细胞白血病 (CLL) 患者外周血单核细胞 (PBMC) 中几个 KLK 基因与健康献血者相比的差异 mRNA 表达的初步结果，我们决定研究 KLK14 mRNA 表达在 CLL 中的诊断和预后潜力。方法：从 69 名 CLL 患者和 31 名非白血病献血者中分离总 RNA。 Poly(A)-RNA 逆转录后，使用灵敏且准确的定量实时 PCR (qPCR) 方法对 KLK14 mRNA 水平进行定量。结果：根据 ROC 分析，KLK14 mRNA 过表达成功区分了 CLL 患者和正常人群（曲线下面积 [AUC] 0.89，95% 置信区间 [CI] 0.83-0.95，p < 0.001）。此外，尽管与临床分期或其他预后因素（包括 IGHV 突变状态和 CD38 表达）没有明确关系，但使用 Kaplan-Meier 生存分析，KLK14 mRNA 的强表达可预测 CLL 患者的总生存期降低（p = 0.026）。多变量 Cox 回归分析显示，CLL 患者 PBMC 中 KLK14 mRNA 过表达的不利预后价值与疾病的既定预后因素无关（风险比 [HR] 14.65，95% CI 1.81-118.36，p = 0.012）。结论：KLK14 mRNA 表达作为潜在的预后指标值得进一步研究CLL 患者总生存期的生物标志物。
Background: Tissue kallikrein and kallikrein-related peptidases (KLKs) compose a family of serine endopeptidases with much clinical interest in oncology, as their potential as diagnostic and/ or prognostic molecular biomarkers in several human malignancies has already been evidenced. However, none of the members of this family has ever been studied in hematological malignancies. Based on our preliminary results regarding the differential mRNA expression of several KLK genes in peripheral blood mononuclear cells (PBMCs) of patients with chronic lymphocytic leukemia (CLL) compared to healthy blood donors, we decided to study the diagnostic and prognostic potential of KLK14 mRNA expression in CLL.Methods: Total RNA was isolated from 69 CLL patients and 31 non-leukemic blood donors. After reverse transcription of poly(A)-RNA, KLK14 mRNA levels were quantified using a sensitive and accurate quantitative real-time PCR (qPCR) methodology.Results: According to ROC analysis, KLK14 mRNA over-expression successfully discriminated CLL patients from normal population (area under the curve [AUC] 0.89, 95% confidence interval [CI] 0.83-0.95, p < 0.001). Moreover, although not clearly related to clinical staging or other prognostic factors including IGHV mutational status and CD38 expression, strong KLK14 mRNA expression was shown to predict reduced overall survival of CLL patients (p = 0.026) using Kaplan-Meier survival analysis. The unfavorable prognostic value of KLK14 mRNA overexpression in CLL patients' PBMCs was independent of established prognostic factors of the disease, as shown by multivariate Cox regression analysis (hazard ratio [HR] 14.65, 95% CI 1.81-118.36, p = 0.012).Conclusions: KLK14 mRNA expression merits further investigation as a potential prognostic biomarker of overall survival of patients with CLL.