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结直肠癌中激肽释放酶相关肽酶10(KLK10)的表达分析及临床评估

Expression analysis and clinical evaluation of kallikrein-related peptidase 10 (KLK10) in colorectal cancer.

作者信息

Talieri Maroulio, Alexopoulou Dimitra K, Scorilas Andreas, Kypraios Dimitris, Arnogiannaki Niki, Devetzi Marina, Patsavela Matina, Xynopoulos Dimitris

机构信息

Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, Saint Savvas Cancer Hospital, 171, Alexandras Avenue, Athens, 11522, Greece.

出版信息

Tumour Biol. 2011 Aug;32(4):737-44. doi: 10.1007/s13277-011-0175-4. Epub 2011 Apr 12.

DOI:10.1007/s13277-011-0175-4
PMID:21487810
Abstract

Kallikrein-related peptidases (KLKs) represent a serine protease family having 15 members. KLK10 is a secreted protease with a trypsin-like activity. The function of KLK10 is poorly understood, although it has been suggested that KLK10 may function as a tumor suppressor gene. In human cancer, KLK10 gene shows organ-specific up- or down-regulation. Since KLKs are promising tumor biomarkers, the examination of KLK10 mRNA expression and its association with colorectal cancer (CRC) progression was studied using semi-quantitative PCR. One hundred and nineteen primary CRC specimens were examined for which follow-up information was available for a median period of 29 months (range, 1-104 months). KLK10 expression was found to be significantly associated with TNM stage (p=0.028). Cox proportional hazard regression model using univariate analysis revealed for the first time that high status KLK10 expression is a significant factor for disease-free survival (DFS; p=0.002) and overall survival (OS; p=0.026) of patients. Kaplan-Meier survival curves demonstrated that KLK10 expression of low status is significantly associated with longer DFS (p=0.001) as well as OS (p=0.021), suggesting that KLK10 gene expression may be used as a marker of unfavorable prognosis for CRC. As the epigenetics of cancer are unraveled, KLK10 may represent not only a novel biomarker, but also a promising future therapeutic target for the disease.

摘要

激肽释放酶相关肽酶(KLKs)是一个包含15个成员的丝氨酸蛋白酶家族。KLK10是一种具有胰蛋白酶样活性的分泌型蛋白酶。尽管有人提出KLK10可能作为一种肿瘤抑制基因发挥作用,但其功能仍知之甚少。在人类癌症中,KLK10基因表现出器官特异性的上调或下调。由于KLKs是很有前景的肿瘤生物标志物,因此使用半定量PCR研究了KLK10 mRNA表达及其与结直肠癌(CRC)进展的关系。对119例原发性CRC标本进行了检查,这些标本的随访信息中位数为29个月(范围1 - 104个月)。发现KLK10表达与TNM分期显著相关(p = 0.028)。单因素分析的Cox比例风险回归模型首次显示,KLK10高表达状态是患者无病生存期(DFS;p = 0.002)和总生存期(OS;p = 0.026)的重要因素。Kaplan - Meier生存曲线表明,KLK10低表达状态与更长的DFS(p = 0.001)以及OS(p = 0.021)显著相关,这表明KLK10基因表达可能用作CRC预后不良的标志物。随着癌症表观遗传学的逐步揭示,KLK10可能不仅代表一种新型生物标志物,而且是该疾病未来有前景的治疗靶点。

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