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激肽释放酶相关肽酶5的上调与结直肠癌的恶性行为相关。

Upregulation of kallikrein‑related peptidase 5 is associated with the malignant behavior of colorectal cancer.

作者信息

Wu Yanhua, Chen Yingjian, Li Qing, Gong Yanwen, Liu Xiaohong, Bi Liquan, Hu Chengjin

机构信息

Department of Laboratory Medicine, General Hospital of Jinan Military Command, Jinan, Shandong 250031, P.R. China.

Department of Clinical Laboratory, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277102, P.R. China.

出版信息

Mol Med Rep. 2016 Sep;14(3):2164-70. doi: 10.3892/mmr.2016.5516. Epub 2016 Jul 13.

DOI:10.3892/mmr.2016.5516
PMID:27430713
Abstract

Kallikrein-related peptidase 5 (KLK5) is a serine protease that has exhibited upregulated expression in numerous types of human cancer. The present study assessed KLK5 expression in colorectal cancer (CRC) tissues, in order to determine its association with clinicopathological data and prognosis. The mRNA and protein expression levels of KLK5 were detected using reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and enzyme‑linked immunosorbent assay, respectively. KLK5 expression was detected in 48 paraffin‑embedded tumor tissue samples and corresponding tumor‑free areas within the same specimens, 40 paired normal and CRC frozen tissues, and serum samples from 70 patients with CRC (including 38 serum samples taken pre‑ and post‑surgery) and 53 healthy individuals. The results demonstrated that KLK5 protein was strongly expressed in CRC; however, its expression was hardly detected in the matched normal mucosal tissue. The KLK5 mRNA expression levels were significantly upregulated in CRC tissues compared with the paired normal tissues, and were higher in Dukes' stage C/D cancer than in stage A/B (P<0.001). Furthermore, sera from patients with CRC exhibited increased KLK5 levels, as compared with that of healthy volunteers (878.02 vs. 391.07 pg/ml; P<0.001). Serum KLK5 levels were also significantly higher in patients prior to surgery compared with post‑surgery (909.48±536.72 vs. 644.00±522.87 pg/ml; P<0.001). In addition, increased serum KLK5 levels were associated with CRC lymph node or distant metastasis (P=0.003), tumor‑lymph node‑metastasis stage (P=0.004), and Dukes' stage (P=0.005). The results of the present study indicated that the mRNA and protein expression levels of KLK5 were significantly upregulated in CRC tissues and sera, and were associated with an advanced tumor stage. Further studies may identify KLK5 as a biomarker of CRC recurrence or treatment response.

摘要

激肽释放酶相关肽酶5(KLK5)是一种丝氨酸蛋白酶,已发现在多种类型的人类癌症中表达上调。本研究评估了KLK5在结直肠癌(CRC)组织中的表达,以确定其与临床病理数据及预后的关系。分别采用逆转录-定量聚合酶链反应、免疫组织化学和酶联免疫吸附测定法检测KLK5的mRNA和蛋白表达水平。在48个石蜡包埋的肿瘤组织样本及其同一标本中的相应癌旁区域、40对正常和CRC冰冻组织以及70例CRC患者(包括38例手术前后采集的血清样本)和53例健康个体的血清样本中检测KLK5表达。结果表明,KLK5蛋白在CRC中高表达;然而,在匹配的正常黏膜组织中几乎检测不到其表达。与配对的正常组织相比,CRC组织中KLK5 mRNA表达水平显著上调,且在Dukes C/D期癌症中高于A/B期(P<0.001)。此外,与健康志愿者相比,CRC患者血清中KLK5水平升高(878.02对391.07 pg/ml;P<0.001)。术前患者血清KLK5水平也显著高于术后(909.48±536.72对644.00±522.87 pg/ml;P<0.001)。此外,血清KLK5水平升高与CRC淋巴结或远处转移(P=0.003)、肿瘤-淋巴结-转移分期(P=0.004)和Dukes分期(P=0.005)相关。本研究结果表明,CRC组织和血清中KLK5的mRNA和蛋白表达水平显著上调,并与肿瘤晚期相关。进一步研究可能会将KLK5鉴定为CRC复发或治疗反应的生物标志物。

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