TERT copy gain predicts the outcome of high-dose interferon α-2b therapy in acral melanoma.
TERT copy gain predicts the outcome of high-dose interferon α-2b therapy in acral melanoma.
复制标题
TERT 拷贝增益可预测高剂量干扰素 α-2b 治疗肢端黑色素瘤的结果
DOI：
10.2147/ott.s158239
复制
发表时间：
2018
影响因子：
4
通讯作者：
Guo J
中科院分区：
文献类型：
--
作者：
Yu S;Xu T;Dai J;Ma M;Tang H;Chi Z;Si L;Cui C;Sheng X;Kong Y;Guo J
亚洲人群比白人更容易患肢端黑色素瘤（AM）。大剂量干扰素（HD-IFN）α-2b方案是AM的主要辅助治疗方案。端粒酶逆转录酶（TERT）编码端粒酶逆转录酶的催化亚基，在黑色素瘤中起重要作用。AM中描述了频繁的TERT突变和增加的TERT基因表达。我们的研究旨在调查大型AM患者队列中TERT拷贝数的状况及其临床意义，并分析TERT拷贝数增加与HD-IFN疗效之间的关系。回顾性收集了总共573个黑素瘤样品，并通过桑格测序分析了TERT拷贝数。同时收集患者的临床资料。在573例AM患者中，257例（44.9%）检测到TERT拷贝数增加（拷贝数>2）。在573例患者中，81例（14.1%）具有高拷贝增益（拷贝数>4）。有溃疡的患者与无溃疡的患者相比显示出显著更高的TERT拷贝增加率（P=0.028）。肿瘤厚度大于4 mm的患者也比肿瘤厚度小于4 mm的患者具有更高的TERT拷贝数率（P=0.048）。我们的研究结果表明，总生存期（OS）之间没有显着差异的患者和没有TERT拷贝增益（P=0.890）。然而，在接受HD-IFN方案的278例患者中，Kaplan-Meier生存分析显示了TERT拷贝获得与无复发生存（RFS）之间的显著相关性（P=0.008）。此外，多变量考克斯回归分析验证了TERT拷贝增加是接受HD-IFN治疗的AM患者RFS的独立预后因素（风险比=1.50; P=0.019）。端粒酶逆转录酶拷贝数可能是HD-IFN疗效的预测因子，但不是AM患者OS的预后因子。
Asian populations are more likely to develop acral melanoma (AM) than Caucasians. The high-dose interferon (HD-IFN) α-2b regimen is the main adjuvant treatment for AM. TERT encodes the catalytic subunit of telomerase reverse transcriptase, which plays an important role in melanoma. Frequent TERT mutation and increased TERT gene expression have been described in AM. Our study aimed to investigate the status and the clinical significance of TERT copy number in a large cohort of patients with AM and to analyze the relationship between TERT copy number gain and the efficiency of HD-IFN. A total of 573 melanoma samples were retrospectively collected and analyzed for TERT copy number via Sanger sequencing. Clinical data of patients were also collected. TERT copy gain (copy number >2) was detected in 257 of the 573 patients with AM (44.9%). Of the 573 patients, 81 (14.1%) had a high copy gain (copy number >4). Patients with ulceration showed a significantly higher copy gain rate of TERT compared to the patients without ulceration (P=0.028). Patients with a tumor thicker than 4 mm also had a higher copy number rate of TERT than those with <4 mm (P=0.048). Our results showed that the overall survival (OS) was not significantly different between patients with and without TERT copy gain (P=0.890). However, among the 278 patients who received an HD-IFN regimen, Kaplan–Meier survival analysis demonstrated a significant correlation between TERT copy gain and relapse-free survival (RFS) (P=0.008). In addition, multivariate Cox regression assays validated TERT copy gain to be an independent prognostic factor of RFS for patients with AM undergoing HD-IFN therapy (hazard ratio =1.50; P=0.019). The copy number status of TERT might be a predictor for HD-IFN efficacy, but it is not a prognostic factor of OS in patients with AM.