Kos J, Stabuc B, Schweiger A, Krasovec M, Cimerman N, Kopitar-Jerala N, Vrhovec I
Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, 1000 Ljubljana, Slovenia.
Clin Cancer Res. 1997 Oct;3(10):1815-22.
The levels of cathepsins (Cats) B, H, and L and their inhibitors stefin A and cystatin C were determined in the sera of 43 patients with metastatic melanoma, in 54 patients with treated cutaneous melanoma with no evidence of metastatic disease, and in 30 healthy blood donors, using quantitative ELISAs. The levels of Cats B and H and cystatin C were significantly higher within the group of metastatic melanoma patients compared with the healthy controls. The median Cat B was 4.8 versus 3.6 ng/ml (P < 0.013), the median Cat H was 13.7 versus 4.9 ng/ml (P < 0.0001), and the median cystatin C was 470 versus 320 ng/ml (P < 0.02). Cat H was also significantly increased within the group of melanoma patients with no metastasis, with a median of 9.6 ng/ml. Cat B was found to correlate with Cat L (r = 0.36; P < 0.02) and cystatin C (r = 0.41; P < 0.008). The serum level of Cat H was significantly increased in patients showing no response to the chemoimmunotherapy as compared to the level in responders. Metastatic melanoma patients with high contents of Cat B and Cat H experienced significantly shorter overall survival rates than the patients with low levels of each enzyme (Cat B: P < 0.003 and relative risk, 2.5; Cat H: P < 0.006 and relative risk, 2.4, using medians as cutoff values). The other potential factors for prognosis for this group of patients revealed moderate (histological type and age) or no (tumor thickness, sex, and lymph node metastasis) prognostic significance. Similarly, no difference in survival was found for stefin A, cystatin C, and Cat L. These results suggest that the serum levels of Cats B and H could serve as prognostic factors for patients with advanced melanoma.
采用定量酶联免疫吸附测定法（ELISA），对43例转移性黑色素瘤患者、54例经治疗但无转移性疾病证据的皮肤黑色素瘤患者以及30名健康献血者的血清中组织蛋白酶（Cats）B、H和L及其抑制剂丝氨酸蛋白酶抑制剂A和胱抑素C的水平进行了测定。与健康对照组相比，转移性黑色素瘤患者组中Cats B和H以及胱抑素C的水平显著更高。组织蛋白酶B的中位数为4.8 ng/ml，而健康对照组为3.6 ng/ml（P < 0.013）；组织蛋白酶H的中位数为13.7 ng/ml，而健康对照组为4.9 ng/ml（P < 0.0001）；胱抑素C的中位数为470 ng/ml，而健康对照组为320 ng/ml（P < 0.02）。在无转移的黑色素瘤患者组中，组织蛋白酶H也显著升高，中位数为9.6 ng/ml。发现组织蛋白酶B与组织蛋白酶L（r = 0.36；P < 0.02）和胱抑素C（r = 0.41；P < 0.008）相关。与有反应的患者相比，对化学免疫疗法无反应的患者血清中组织蛋白酶H水平显著升高。组织蛋白酶B和H含量高的转移性黑色素瘤患者的总生存率显著低于每种酶水平低的患者（以中位数作为临界值，组织蛋白酶B：P < 0.003，相对风险为2.5；组织蛋白酶H：P < 0.006，相对风险为2.4）。该组患者的其他潜在预后因素显示出中等（组织学类型和年龄）或无（肿瘤厚度、性别和淋巴结转移）预后意义。同样，在丝氨酸蛋白酶抑制剂A、胱抑素C和组织蛋白酶L方面未发现生存差异。这些结果表明，组织蛋白酶B和H的血清水平可作为晚期黑色素瘤患者的预后因素。
