激活的Akt表达与原发性黑色素瘤的复发有关，并进一步细化了对阴毛黑色素瘤复发的预后和预测价值。
Activated Akt expression is associated with the recurrence of primary melanomas and further refines the prognostic and predictive values for relapse in acral melanomas.
发表日期：2023 Aug 18
作者：
Kohei Nojima, Masahiro Hayashi, Atsushi Tanemura, Hind Al-Busani, Toru Saito, Tamio Suzuki, Masashi Ishikawa, Taisuke Mori, Shogo Wada, Naoya Yamazaki, Ichiro Katayama, Hiroki Mori, Hiroo Yokozeki, Naoko Okiyama, Yoshiyuki Sasaki, Takeshi Namiki
来源：
Pigment Cell & Melanoma Research
摘要：
PTEN缺陷导致丝氨酸473位的磷酸化Akt（p-Akt）的激活，并通过与NUAK2扩增相结合促进黑色素瘤的肿瘤发生。我们测试了p-Akt和/或NUAK2表达对黑色素瘤患者复发无病生存期（RFS）和总生存期（OS）的预后影响。使用免疫组织化学检查了112例扩散黑色素瘤患者、38例低累积阳光损伤（CSD）黑色素瘤患者和18例高CSD黑色素瘤患者的原发肿瘤，并统计分析了它们的预后意义。p-Akt表达分别在扩散型黑色素瘤、低CSD黑色素瘤和高CSD黑色素瘤中发现为32.1%、68.4%和55.6%，而NUAK2表达分别为46.4%、76.3%和50.0%。无论是p-Akt还是NUAK2的表达都与原发黑色素瘤患者和扩散型黑色素瘤患者的RFS呈负相关（p-Akt：p < .0001，p < .0001；NUAK2：p = .0005，p < .0001）。引人注目的是，多变量分析显示p-Akt对RFS有显著影响（风险比 = 4.454；p < .0001），而NUAK2没有。进一步的亚组分析表明，p-Akt的表达对扩散型黑色素瘤患者的RFS有不良影响（风险比 = 4.036；p = .0005）。我们得出结论，p-Akt的表达对原发黑色素瘤患者的RFS有显著影响，可以预测扩散型黑色素瘤患者的复发。© 2023 John Wiley & Sons A/S. John Wiley & Sons Ltd.发表。
A PTEN deficiency leads to the activation of phospho-Akt at serine 473 (p-Akt) and promotes the tumorigenesis of melanomas by coupling with NUAK2 amplification. We tested the prognostic impact of p-Akt and/or NUAK2 expression on the relapse-free survival (RFS) and overall survival (OS) of melanoma patients. Primary tumors from patients with acral melanomas (112), Low-cumulative sun damage (CSD) melanomas (38), and High-CSD melanomas (18) were examined using immunohistochemistry and their prognostic significance was analyzed statistically. The expression of p-Akt was found in 32.1%, 68.4%, and 55.6% of acral, Low-CSD, and High-CSD melanomas, while NUAK2 expression was found in 46.4%, 76.3%, and 50.0%, respectively. Either p-Akt or NUAK2 expression was inversely correlated with the RFS of primary melanoma patients and acral melanoma patients (p-Akt: p < .0001, p < .0001; NUAK2; p = .0005, p < .0001, respectively). Strikingly, multivariate analyses revealed that p-Akt had a significant impact on RFS (Hazard ratio = 4.454; p < .0001), while NUAK2 did not. Further subset analyses revealed that p-Akt expression had an inferior RFS of patients with acral melanomas (Hazard ratio = 4.036; p = .0005). We conclude that the expression of p-Akt has a significant impact on RFS of patients with primary melanomas and can predict the relapse of patients with acral melanomas.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.