Prognostic Significance of RUNX3 Expression in Human Melanoma
Prognostic Significance of RUNX3 Expression in Human Melanoma
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DOI：
10.1002/cncr.25838
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发表时间：
2011-06-15
期刊：
影响因子：
6.2
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Zhang, Zhizhong;Chen, Guangdi;Li, Gang
背景：RUNX3是一种肿瘤抑制因子，在细胞增殖、凋亡和转移中起重要作用。作者研究了RUNX3在黑色素瘤发病机制中的作用，并在大量黑色素瘤患者中分析了RUNX3表达对预后的影响。方法：构建两组组织微阵列，包括440例黑色素瘤（训练组202例，验证组238例）和88例痣（正常痣25例，发育不良痣63例）。免疫组织化学检测RUNX3的表达。结果：RUNX3阳性表达在正常痣、发育不良痣、原发性黑色素瘤和黑色素瘤转移灶的活检中分别占56%、54%、33%和24%。核RUNX3阳性染色在发育不良痣与原发性黑色素瘤之间（P = 0.002，卡方检验）、发育不良痣与黑色素瘤转移之间（P < 0.001，卡方检验）、原发性黑色素瘤与黑色素瘤转移之间（P = 0.045，卡方检验）均有显著差异。在训练组和验证组中，RUNX3表达的缺失与黑色素瘤患者较差的5年生存率相关。此外，RUNX3表达缺失也与原发性黑色素瘤（P = 0.001）和转移性黑色素瘤（P = 0.008）患者较差的5年疾病特异性生存率相关。多因素Cox回归分析显示，RUNX3阳性表达是预测黑色素瘤患者预后的独立预后因素。结论：我们的研究结果表明，RUNX3在黑色素瘤的发病机制中起着重要作用，可能是黑色素瘤的一个有希望的预后标志物。癌症2011;117: 2719 - 27所示。(C) 2010年美国癌症协会。
BACKGROUND: RUNX3 is a tumor suppressor that plays important roles in cell proliferation, apoptosis, and metastasis. The authors investigated the role of RUNX3 in melanoma pathogenesis and analyzed the prognostic impact of RUNX3 expression in a large series of melanoma patients. METHODS: Two sets of tissue microarrays were constructed, including 440 cases of melanomas (202 for the training set and 238 for the validation set) and 88 cases of nevi (25 normal nevi and 63 dysplastic nevi). RUNX3 expression was evaluated by immunohistochemistry. RESULTS: Positive RUNX3 expression was observed in 56%, 54%, 33%, and 24% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for positive nuclear RUNX3 staining were observed between dysplastic nevi and primary melanomas (P = .002, chi-square test), between dysplastic nevi and melanoma metastases (P < .001, chi-square test), and between primary melanoma and melanoma metastases (P = .045, chi-square test). Loss of RUNX3 expression was correlated with a worse 5-year survival of melanoma patients in both training and validation sets. Furthermore, loss of RUNX3 expression was also correlated with a poor 5-year disease-specific survival in primary melanoma (P = .001) and metastatic melanoma patients (P = .008). Multivariate Cox regression analysis revealed that positive RUNX3 expression is an independent prognostic factor to predict melanoma patient outcome. CONCLUSIONS: Our findings indicate that RUNX3 plays an important role in melanoma pathogenesis and may serve as a promising prognostic marker for melanoma. Cancer 2011; 117: 2719-27. (C) 2010 American Cancer Society.