Department of Dermatology and Skin Science, Molecular Medicine Lab, The University of British Columbia.
Vancouver Coastal Health Research Institute, Vancouver, Canada.
Melanoma Res. 2021 Apr 1;31(2):173-177. doi: 10.1097/CMR.0000000000000720.
Lysyl oxidase-like 3 (LOXL3) is an extracellular enzyme involved in the synthesis of collagen and elastin, and it has been reported to promote melanoma cell proliferation and invasion in vitro. However, the expression level of LOXL3 at different stages of melanocytic lesions and the role of LOXL3 in melanoma pathogenesis remain unknown. Immunohistochemical staining of LOXL3 in a tissue microarray of 373 biopsies at different melanocytic stages was conducted. The correlation between LOXL3 expression and patient survival was examined using Kaplan-Meier survival analysis. Univariate and multivariate Cox regression analyses were conducted to study the hazard ratios. The tissue microarray study revealed that stronger expression of LOXL3 protein was found at more advanced melanocytic stages (P < 0.0001; χ2 test). Increased LOXL3 expression was associated with enhanced tumor thickness and mitosis. Survival analysis showed significantly worsened prognosis in primary melanoma patients when the LOXL3 expression level was higher (P = 0.043; log-rank test). Multivariate Cox regression analysis further showed that LOXL3 expression is a prognostic factor for primary melanoma patient survival (P = 0.04). LOXL3 expression is positively correlated with tumor progression and invasion, and its overexpression is associated with worse prognosis of primary melanoma patients. LOXL3 can serve as a prognostic marker to help identify primary melanoma patients at higher risks of death.
赖氨酰氧化酶样蛋白 3(LOXL3)是一种参与胶原蛋白和弹性蛋白合成的细胞外酶,已有报道称其在体外促进黑色素瘤细胞增殖和侵袭。然而,LOXL3 在黑色素细胞病变的不同阶段的表达水平以及 LOXL3 在黑色素瘤发病机制中的作用尚不清楚。对 373 份不同黑色素细胞阶段活检组织微阵列中的 LOXL3 进行免疫组织化学染色。采用 Kaplan-Meier 生存分析检测 LOXL3 表达与患者生存的相关性。采用单因素和多因素 Cox 回归分析研究风险比。组织微阵列研究表明,LOXL3 蛋白表达在更晚期的黑色素细胞阶段更强(P<0.0001;卡方检验)。LOXL3 表达增加与肿瘤厚度和有丝分裂增加相关。生存分析显示,当 LOXL3 表达水平较高时,原发性黑色素瘤患者的预后明显恶化(P=0.043;对数秩检验)。多因素 Cox 回归分析进一步表明,LOXL3 表达是原发性黑色素瘤患者生存的预后因素(P=0.04)。LOXL3 表达与肿瘤进展和侵袭呈正相关,其过表达与原发性黑色素瘤患者预后较差相关。LOXL3 可作为一种预后标志物,有助于识别具有更高死亡风险的原发性黑色素瘤患者。