Liu Xianwu, Quan Bin, Tian Zhilong, Xi Hailin, Jia Gaolei, Wang Hui, Zhang Liang, Liu Ruming, Ma Cheng, Han Fuzhou, Li Huansong, Yuan Fukang
Department of General Surgery, The Second Affiliated Hospital of Xuzhou Medical University, 32 Meijian Road, Xuzhou, 221006, Jiangsu, China.
Department of General Surgery, XuZhou Central Hospital, 199 Jiefang Road, Xuzhou, 221009, Jiangsu, China.
Biomed Pharmacother. 2017 Apr;88:595-602. doi: 10.1016/j.biopha.2017.01.112. Epub 2017 Jan 28.
KLK8, also known as neuropsin, is one of fifteen members of the human kallikrein-related peptidase (KLK) gene family, which consists of enzymes with serine protease enzymatic activity. Aberrant KLK8 expression has been reported in several malignancies. However, the clinicopathological significance and prognostic value of KLK8 expression in colorectal cancer (CRC) are unknown. Therefore, analysis of public datasets, quantitative real-time PCR and western blot analysis were performed to assess KLK8 expression in CRC at both the mRNA and protein level. KLK8 expression was also assessed by immunohistochemistry in a tissue microarray containing 124 CRC specimens. We observed that KLK8 was overexpressed in CRC tissues and was significantly associated with TNM stage, vascular invasion, differentiation and AJCC stage. Univariate and multivariate Cox analyses confirmed that KLK8 is a significant independent prognostic factor for both DFS and OS. Cell function assays also indicated that KLK8 could facilitate CRC cell proliferation, migration and invasion in vitro. In conclusion, elevated KLK8 expression was correlated with the progression of CRC and is a potential independent prognostic indicator for CRC.
KLK8，也称为神经蛋白酶，是人类激肽释放酶相关肽酶（KLK）基因家族的15个成员之一，该家族由具有丝氨酸蛋白酶酶活性的酶组成。已有报道称KLK8在多种恶性肿瘤中表达异常。然而，KLK8在结直肠癌（CRC）中的临床病理意义和预后价值尚不清楚。因此，我们进行了公共数据集分析、定量实时PCR和蛋白质印迹分析，以评估CRC中KLK8在mRNA和蛋白质水平的表达。我们还通过免疫组织化学在一个包含124个CRC标本的组织芯片中评估了KLK8的表达。我们观察到KLK8在CRC组织中过表达，并且与TNM分期、血管侵犯、分化程度和AJCC分期显著相关。单因素和多因素Cox分析证实，KLK8是DFS和OS的一个重要独立预后因素。细胞功能实验还表明，KLK8在体外可促进CRC细胞的增殖、迁移和侵袭。总之，KLK8表达升高与CRC的进展相关，是CRC潜在的独立预后指标。
