Department of Biochemistry and Molecular Biology, University of Athens, Athens GR-15701, Greece.
Clin Biochem. 2013 Oct;46(15):1453-61. doi: 10.1016/j.clinbiochem.2013.03.002. Epub 2013 Mar 13.
Colorectal cancer (CRC) is one of the three most common cancers in both genders. Even though several biomarkers are in use in diagnosis and prognosis of the disease, they are marred by limited specificity and sensitivity. The human kallikrein-related peptidase 10 (KLK10) gene is a member of the human tissue kallikrein family. Because prostate specific antigen (PSA), the best biomarker for detecting and monitoring prostate cancer, is a member of this family, many other members, including KLK10, have been widely examined as novel biomarkers for different cancer types. In previous studies, KLK10 has been proposed as a diagnostic biomarker for ovarian carcinoma, while its methylation on exon 3 has been proposed as a prognostic marker for early-stage breast cancer patients. The purpose of this study was to analyse KLK10 mRNA expression and examine its prognostic value and potential clinical application as a novel molecular tissue biomarker in CRC.
The study group consisted of 190 colorectal samples. Total RNA was extracted from pulverised tissues and cDNA was prepared by reverse transcription. KLK10 was amplified by real-time PCR. B2M was used as a reference gene and HT-29 cells as positive control.
KLK10 expression was significantly higher in cancer tissues (P<0.001). Tumours of advanced TNM and Dukes' stage showed high KLK10 expression status (P=0.036; P=0.025). Patients with high KLK10 expression had a shorter disease-free and overall survival rates (P=0.014; P=0.020).
Our results suggest that KLK10 may serve as a new marker of unfavourable prognosis of colorectal cancer.
结直肠癌(CRC)是男性和女性中最常见的三种癌症之一。尽管有几种生物标志物用于该疾病的诊断和预后,但它们的特异性和敏感性有限。人激肽释放酶相关肽 10(KLK10)基因是人类组织激肽释放酶家族的成员。由于前列腺特异性抗原(PSA)是检测和监测前列腺癌的最佳生物标志物,是该家族的成员,许多其他成员,包括 KLK10,已被广泛研究作为不同癌症类型的新型生物标志物。在之前的研究中,KLK10 被提议作为卵巢癌的诊断生物标志物,而其外显子 3 的甲基化被提议作为早期乳腺癌患者的预后标志物。本研究旨在分析 KLK10 mRNA 表达,并研究其作为 CRC 新型分子组织生物标志物的预后价值和潜在临床应用。
研究组包括 190 例结直肠样本。从粉碎组织中提取总 RNA,并通过逆转录制备 cDNA。通过实时 PCR 扩增 KLK10。B2M 用作参考基因,HT-29 细胞用作阳性对照。
癌症组织中 KLK10 的表达明显更高(P<0.001)。TNM 和 Dukes'分期较晚的肿瘤显示出高 KLK10 表达状态(P=0.036;P=0.025)。KLK10 高表达的患者无病生存期和总生存期较短(P=0.014;P=0.020)。
我们的结果表明 KLK10 可能作为结直肠癌不良预后的新标志物。