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SRY-box 基因 17 的表达降低与黑色素瘤患者预后不良相关。

Reduced expression of SRY-box containing gene 17 correlates with an unfavorable melanoma patient survival.

机构信息

Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1L8, Canada.

Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.

出版信息

Oncol Rep. 2014 Dec;32(6):2571-9. doi: 10.3892/or.2014.3534. Epub 2014 Oct 8.

Abstract

SRY-box containing gene 17 (Sox17), a transcription factor, is considered as an antagonist to canonical Wnt/β‑catenin signaling in several types of malignant tumors. As the influence of Sox17 in the pathogenesis of human melanoma is still unknown, the investigation of Sox17 expression in melanoma is warranted and its prognostic value is of great interest. In the present study, Sox17 expression was examined in 525 cases of melanocytic lesions (33 common acquired nevi, 59 dysplastic nevi, 291 primary melanomas and 142 metastatic melanomas) at different stages by tissue microarray. The correlation of Sox17 expression with melanoma progression and its prognostic value in melanoma patients were examined. We also analyzed the correlation between Sox17 and cyclin-dependent kinase inhibitor p27 expression in 374 melanoma samples. The results showed that Sox17 expression was significantly decreased in primary and metastatic melanoma compared to common acquired nevi and dysplastic nevi (P=2.4x10-17). Furthermore, Sox17 expression was inversely correlated with American Joint Committee on Cancer stage (P=4.6x10-15), thickness (P=0.00004) and ulceration (P=0.03). Notably, reduced Sox17 expression was correlated with a poorer overall and disease-specific 5- and 10-year survival of the patients. Multivariate Cox regression analyses indicated that Sox17 is an independent prognostic marker for melanoma patients. Moreover, we found a significant positive correlation between Sox17 and p27 expression in melanoma biopsies; their concomitant expression was closely correlated with the survival of melanoma patients. Taken together, decreased Sox17 expression is correlated with melanoma progression, an unfavorable survival of melanoma patients and is an independent molecular prognostic factor for melanoma.

摘要

性别决定区 Y 框蛋白 17(Sox17)是一种转录因子,被认为是几种类型恶性肿瘤中经典 Wnt/β-连环蛋白信号通路的拮抗剂。由于 Sox17 在人类黑色素瘤发病机制中的影响尚不清楚,因此有必要研究 Sox17 在黑色素瘤中的表达情况,其预后价值也备受关注。本研究通过组织微阵列检测了 525 例黑素细胞病变(33 例常见获得性痣、59 例发育不良痣、291 例原发性黑素瘤和 142 例转移性黑素瘤)中 Sox17 的表达情况,分析了 Sox17 表达与黑色素瘤进展的相关性及其在黑色素瘤患者中的预后价值,并在 374 例黑色素瘤样本中分析了 Sox17 与细胞周期蛋白依赖性激酶抑制剂 p27 表达的相关性。结果表明,与常见获得性痣和发育不良痣相比,原发性和转移性黑色素瘤中 Sox17 的表达显著降低(P=2.4x10-17)。此外,Sox17 表达与美国癌症联合委员会分期(P=4.6x10-15)、厚度(P=0.00004)和溃疡(P=0.03)呈负相关。值得注意的是,Sox17 表达降低与患者的总生存率和疾病特异性 5 年及 10 年生存率较差相关。多变量 Cox 回归分析表明 Sox17 是黑色素瘤患者的独立预后标志物。此外,我们发现黑色素瘤活检中 Sox17 与 p27 表达之间存在显著的正相关;它们的共同表达与黑色素瘤患者的生存密切相关。综上所述,Sox17 表达降低与黑色素瘤进展、黑色素瘤患者不良生存相关,是黑色素瘤的独立分子预后因素。

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