Janecka-Widła Anna, Majchrzyk Kaja, Mucha-Małecka Anna, Słonina Dorota, Biesaga Beata
Department of Tumour Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Garncarska 11, 31-115 Cracow, Poland.
Department of Tumour Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Garncarska 11, 31-115 Cracow, Poland.
Pathol Res Pract. 2022 Jan;229:153684. doi: 10.1016/j.prp.2021.153684. Epub 2021 Nov 9.
The prognosis of squamous cell carcinoma of head and neck (HNSCC) patients remains relatively poor over the last years. Tobacco, alcohol and active human papillomavirus (HPV) infection are involved in HNSCC development. Akt is a serine-threonine protein kinase with main phosphorylation sites at Thr308 and Ser473, which are critical to generate a high level of Akt activity.
The aim of the study was to compare the expression and prognostic potential of total Akt and its 2 phosphorylated forms - pAkt(Ser473) and pAkt(Thr308) in relation to HPV status in HNSCC patients. The expression levels of proteins were assessed immunohistochemically. To select independent prognostic factors univariate and multivariate analyses with Cox proportional regression model were performed.
Among HNSCC with active HPV16 infection significantly more tumors with high Akt (67.86%, p = 0.026) and low pAkt(Ser473) (64.29%, p = 0.000) expressions were found as compared to those with HPV negativity, while there was no significant difference in the pAkt(Thr308) expression level between HPV positive and negative tumors (p = 0.359). In the whole group of HNSCC patients independent favorable prognostic factors were low T stage, low pAkt(Thr308) expression, HPV16 active infection presence (for OS and DFS) and female gender (for OS only).
Our results indicate an important role of pAkt(Thr308) as prognostic biomarker for HNSCC patients. There is a high probability that using Akt inhibitors would improve therapeutical benefits and treatment effectiveness, especially in HNSCC patients with high expression of pAkt.
在过去几年中，头颈部鳞状细胞癌（HNSCC）患者的预后仍然相对较差。烟草、酒精和人乳头瘤病毒（HPV）的活跃感染与HNSCC的发生有关。Akt是一种丝氨酸 - 苏氨酸蛋白激酶，其主要磷酸化位点位于Thr308和Ser473，这些位点对于产生高水平的Akt活性至关重要。
本研究的目的是比较HNSCC患者中总Akt及其两种磷酸化形式 - pAkt(Ser473)和pAkt(Thr308)的表达及预后潜力与HPV状态的关系。采用免疫组织化学方法评估蛋白质的表达水平。使用Cox比例回归模型进行单因素和多因素分析以选择独立的预后因素。
在活跃感染HPV16的HNSCC中，与HPV阴性的肿瘤相比，发现有更多肿瘤具有高Akt表达（67.86%，p = 0.026）和低pAkt(Ser473)表达（64.29%，p = 0.000），而HPV阳性和阴性肿瘤之间pAkt(Thr308)表达水平无显著差异（p = 0.359）。在整个HNSCC患者组中，独立的有利预后因素为低T分期、低pAkt(Thr308)表达、HPV16活跃感染的存在（对于总生存期和无病生存期）以及女性性别（仅对于总生存期）。
我们的结果表明pAkt(Thr308)作为HNSCC患者预后生物标志物具有重要作用。使用Akt抑制剂很有可能提高治疗益处和治疗效果，特别是在pAkt高表达的HNSCC患者中。
