Christodoulou Spyridon, Alexopoulou Dimitra K, Kontos Christos K, Scorilas Andreas, Papadopoulos Iordanis N
Fourth Surgery Department, University General Hospital "Attikon", Haidari, Athens, 12462, Greece.
Tumour Biol. 2014 May;35(5):4673-85. doi: 10.1007/s13277-014-1612-y. Epub 2014 Jan 16.
Members of the family of tissue kallikrein and kallikrein-related peptidases possess important prognostic value in cancer. Moreover, the oncogenic role of kallikrein-related peptidase-6 (KLK6) in colorectal cancer has been well documented so far. This study investigated the prognostic value of KLK6 mRNA expression as a molecular tissue biomarker in colorectal adenocarcinoma. For this purpose, KLK6 mRNA expression was studied in 110 primary colorectal adenocarcinomas and 39 paired noncancerous colorectal specimens. A dramatic upregulation of KLK6 mRNA expression was observed in colorectal tumors. KLK6 mRNA overexpression was associated with high depth of tumor invasion, presence of distant metastases, and tumor-node-metastasis (TNM) stage of patients. Furthermore, KLK6 mRNA expression was shown to predict poor disease-free and overall survival independently of patient gender, age, tumor size, location, histological subtype, grade, venous invasion, lymphatic invasion, TNM stage, radiotherapy, and chemotherapy treatment. Moreover, Kaplan-Meier survival analysis revealed that colorectal adenocarcinoma patients with negative regional lymph nodes (N0) and those without distant metastases (M0) harboring KLK6 mRNA-positive colorectal tumors tended to relapse and die earlier than N0 and M0 patients with KLK6 mRNA-negative colorectal adenocarcinoma. Thus, KLK6 mRNA expression could be considered as an independent, unfavorable molecular prognostic biomarker in colorectal adenocarcinoma, with additional prognostic value in patients without regional or distant metastases.
组织激肽释放酶和激肽释放酶相关肽酶家族成员在癌症中具有重要的预后价值。此外，到目前为止，激肽释放酶相关肽酶-6（KLK6）在结直肠癌中的致癌作用已有充分记录。本研究调查了KLK6 mRNA表达作为结直肠腺癌分子组织生物标志物的预后价值。为此，在110例原发性结直肠腺癌和39例配对的非癌性结直肠标本中研究了KLK6 mRNA表达。在结直肠肿瘤中观察到KLK6 mRNA表达显著上调。KLK6 mRNA过表达与肿瘤浸润深度、远处转移的存在以及患者的肿瘤-淋巴结-转移（TNM）分期相关。此外，KLK6 mRNA表达被证明可独立于患者性别、年龄、肿瘤大小、位置、组织学亚型、分级、静脉侵犯、淋巴侵犯、TNM分期、放疗和化疗治疗来预测无病生存期和总生存期较差。此外，Kaplan-Meier生存分析显示，区域淋巴结阴性（N0）且无远处转移（M0）的结直肠腺癌患者，若其KLK6 mRNA阳性的结直肠肿瘤，往往比KLK6 mRNA阴性的N0和M0结直肠腺癌患者更早复发和死亡。因此，KLK6 mRNA表达可被视为结直肠腺癌中一种独立的、不良的分子预后生物标志物，对无区域或远处转移的患者具有额外的预后价值。
