已发表论文

TERT  复制增加可预测高剂量干扰素 α-2b 对肢端黑色素瘤的治疗结果

 

Authors Yu S, Xu T, Dai J, Ma M, Tang H, Chi Z, Si L, Cui C, Sheng X, Kong Y, Guo J

Received 27 November 2017

Accepted for publication 6 April 2018

Published 17 July 2018 Volume 2018:11 Pages 4097—4104

DOI https://doi.org/10.2147/OTT.S158239

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr XuYu Yang

Background: 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.
Patients and methods: 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.
Results: 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 (=0.028). Patients with a tumor thicker than 4 mm also had a higher copy number rate of TERT  than those with <4 mm (=0.048). Our results showed that the overall survival (OS) was not significantly different between patients with and without TERT  copy gain (=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) (=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; =0.019).
Conclusion: 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.
Keywords: acral melanoma, TERT , gene copy number, interferon α-2b, relapse-free survival




Figure 2 Influence of the TERT copy gain on patients’ OS.