Reduced expression of SRY-box containing gene 17 correlates with an unfavorable melanoma patient survival
Reduced expression of SRY-box containing gene 17 correlates with an unfavorable melanoma patient survival
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含有基因 17 的 SRY-box 表达降低与黑色素瘤患者的不利生存相关
DOI：
10.3892/or.2014.3534
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发表时间：
2014-12-01
期刊：
影响因子：
4.2
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Lu, Jing;Zhang, Guohong;Li, Gang
SRY-box含有基因17 (Sox17)，一种转录因子，被认为是几种类型恶性肿瘤中典型Wnt/ β -连环蛋白信号的拮抗剂。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及其预后价值。本研究采用组织芯片技术检测了525例不同阶段黑色素细胞病变（33例常见获得性痣，59例发育不良痣，291例原发性黑色素瘤，142例转移性黑色素瘤）中Sox17的表达。研究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。我们还分析了374例黑色素瘤样本中Sox17与细胞周期蛋白依赖性激酶抑制剂p27表达之间的相关性。结果显示，与普通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=2.4 × 10(-17)）。此外，Sox17表达与American Joint Committee on Cancer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表达减少与患者总体生存率和疾病特异性5年和10年生存率较差相关。多因素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和p27的表达呈正相关；它们的伴随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的进展有关，不利于黑色素瘤患者的生存，是黑色素瘤的独立分子预后因素。
SRY-box containing gene 17 (Sox17), a transcription factor, is considered as an antagonist to canonical Wnt/beta-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.