Decreased expression of nuclear p300 is associated with disease progression and worse prognosis of melanoma patients.
Decreased expression of nuclear p300 is associated with disease progression and worse prognosis of melanoma patients.
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DOI：
10.1371/journal.pone.0075405
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Rotte A;Bhandaru M;Cheng Y;Sjoestroem C;Martinka M;Li G
紫外线辐射引起的基因组不稳定性是黑色素瘤的主要原因之一。组蛋白乙酰转移酶p300在DNA修复和维持基因组完整性中起着不可或缺的作用。本研究旨在分析p300表达、黑色素瘤进展和患者生存率之间的相关性。应用组织芯片和免疫组化技术研究p300在黑色素瘤中的表达。共有358例黑色素瘤患者（250例原发性黑色素瘤和108例转移性黑色素瘤）用于本研究。采用Kaplan-Meier法、单变量和多变量考克斯回归分析以及受试者工作特征曲线来阐明p300表达的预后意义。我们的结果表明，p300在细胞核和细胞质中都有表达，但p300在细胞核中的表达占主导地位。从发育不良痣到原发性黑色素瘤和转移性黑色素瘤的疾病进展与细胞核p300表达减少和细胞质p300表达增加相关。特别是，细胞核的丢失和细胞质p300的获得与黑色素瘤从AJCC II期到III期的进展相关，这需要癌细胞从原发部位迁移和转移到淋巴结。同样，细胞核p300表达减少和细胞质p300表达增加与黑色素瘤患者生存率降低相关。细胞核p300表达与AJCC分期、年龄、性别无关，而细胞浆p300表达与AJCC患者生存率无相关性。核p300表达的缺失是患者生存率较差的指标，也是黑色素瘤的独立预后标志。
Genomic instability due to UV radiation is one of the leading causes for melanoma. Histone acetyltransferase p300 plays an indispensible role in DNA repair and maintenance of genomic integrity. The present study was performed to analyze the correlation between p300 expression, melanoma progression and patient survival. Tissue microarray and immunohistochemical analysis was employed to study the expression of p300 in melanoma patients. A total of 358 melanoma patients (250 primary melanoma and 108 metastatic melanoma) were used for the study. Kaplan-Meier, univariate and multivariate Cox regression analysis, and receiver-operating characteristic curves, were used to elucidate the prognostic significance of p300 expression. Our results demonstrate that p300 is expressed in both nucleus and cytoplasm but the nuclear expression of p300 is predominant. The progression of disease from dysplastic nevi to primary melanoma and to metastatic melanoma was associated with decreased nuclear and increased cytoplasmic p300 expression. Especially, the loss of nuclear and gain in cytoplasmic p300 was correlated with the progression of melanoma from AJCC stage II to stage III, which requires the migration and metastasis of cancer cells from primary sites to lymph nodes. Similarly, decrease in nuclear, and increase in cytoplasmic p300 expression correlated with worse survival of melanoma patients. Nuclear p300 but not cytoplasmic p300 could predict the patient survival independent of AJCC stage, age and gender. Loss of nuclear p300 expression is an indicator of worse patient survival and is an independent prognostic marker for melanoma.
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