Kim H, Scorilas A, Katsaros D, Yousef G M, Massobrio M, Fracchioli S, Piccinno R, Gordini G, Diamandis E P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, M5G 1X5, Canada.
Br J Cancer. 2001 Mar 2;84(5):643-50. doi: 10.1054/bjoc.2000.1649.
Kallikrein gene 5 (KLK5, also known as KLK-L2), located on chromosome 19q13.4, is one of the newly identified members of the kallikrein gene family, which is a subgroup of the serine protease enzyme family. In normal human tissues, KLK5 is highly expressed in skin, mammary gland and testis. Preliminary RT-PCR analysis has indicated that KLK5 is expressed in a subset of ovarian tumours. We have thus hypothesized that KLK5 may be a new prognostic indicator in ovarian cancer. We have examined the mRNA expression of KLK5 in 142 malignant ovarian tissues. Tumours were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK5 was amplified by PCR using gene specific primers, and the identity of the PCR product was verified by sequencing. Ovarian tissues were then classified as KLK5 positive or negative, based on ethidium bromide staining of the PCR product on agarose gels. KLK5 was found to be highly expressed in 58/142 (41%) of ovarian cancer samples while its level of expression was very low in normal ovarian tissues. We found a strong positive relation between KLK5 expression and tumour grade (P = 0.006) and disease stage (P = 0.027). Univariate survival analysis revealed that patients with ovarian tumours positive for KLK5 expression had an increased risk for relapse and death (P = 0.018 and 0.022, respectively). In multivariate analysis, KLK5 expression showed independent prognostic value only in the subset of tumours with lower grade disease (grades I and II). We conclude that KLK5 expression is associated with more aggressive forms of epithelial ovarian carcinoma and has indepdent prognostic value in low grade tumours.
激肽释放酶基因5(KLK5,也称为KLK - L2)位于19号染色体q13.4区域,是激肽释放酶基因家族新鉴定的成员之一,该家族是丝氨酸蛋白酶家族的一个亚组。在正常人体组织中,KLK5在皮肤、乳腺和睾丸中高表达。初步的逆转录聚合酶链反应(RT - PCR)分析表明,KLK5在一部分卵巢肿瘤中表达。因此,我们推测KLK5可能是卵巢癌新的预后指标。我们检测了142例恶性卵巢组织中KLK5的mRNA表达。将肿瘤组织粉碎,提取总RNA,并通过逆转录制备cDNA。使用基因特异性引物通过PCR扩增KLK5,并通过测序验证PCR产物的同一性。然后根据琼脂糖凝胶上PCR产物的溴化乙锭染色,将卵巢组织分为KLK5阳性或阴性。发现58/142(41%)的卵巢癌样本中KLK5高表达,而其在正常卵巢组织中的表达水平非常低。我们发现KLK5表达与肿瘤分级(P = 0.006)和疾病分期(P = 0.027)之间存在强正相关。单因素生存分析显示,KLK5表达阳性的卵巢肿瘤患者复发和死亡风险增加(分别为P = 0.018和0.022)。在多因素分析中,KLK5表达仅在低级别疾病(I级和II级)肿瘤亚组中显示出独立的预后价值。我们得出结论,KLK5表达与更具侵袭性的上皮性卵巢癌相关,并且在低级别肿瘤中具有独立的预后价值。