咽部鳞状细胞癌中MASTL （Greatwall）的表达与良好的预后和放疗应答有关

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-05-20 DOI:10.1016/j.tranon.2025.102417

Esperanza Pozo-Agundo , Miguel Álvarez-González , Israel Rivera-García , Vanessa García-de-la-Fuente , Alba de Martino , Juan Ramón Tejedor , Juan Carlos de Vicente , Juan P. Rodrigo , Juana M. García-Pedrero , Mónica Álvarez-Fernández

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引用次数: 0

摘要

头颈部鳞状细胞癌（HNSCCs）在疾病进展和治疗结果方面具有高度异质性，在临床实践中几乎没有任何分子生物标志物。因此，本研究的目的是研究MASTL/Greatwall在HNSCC中的潜在预后和预测价值，MASTL/Greatwall是一种有丝分裂激酶，也参与PI3K-mTOR信号传导和DNA损伤反应。通过免疫组织化学对346例手术治疗的hpv阴性咽喉鳞癌患者以及64例诱导化疗（ICT）患者的治疗前活检进行了MASTL表达评估。此外，从癌症基因组图谱（TCGA）数据库中分析135例患者的MASTL mRNA表达。MASTL高表达与疾病特异性生存（DSS）的改善显著相关（P = 0.029），特别是在高分化咽部鳞状细胞癌（PSCC）肿瘤中（P = 0.002）。值得注意的是，这种关联仅限于接受辅助放疗（RT）的患者（P = 0.009）。在TCGA数据集的PSCC肿瘤中，在mRNA水平上也发现了类似的相关性。此外，MASTL和p21的联合表达与更好的DSS显著相关，特别是在接受RT的患者中（P = 0.014）。多因素Cox回归分析进一步证实，MASTL高表达与术后接受RT的患者预后良好独立相关(HR= 0.65；95% ci: 0.45-0.94；P = 0.021)。总的来说，这些发现前所未有地揭示了晚期hpv阴性PSCC中MASTL的高表达与良好预后之间的关联，与之前在其他肿瘤类型中的报道形成鲜明对比。重要的是，MASTL表达成为rt治疗PSCC患者良好预后的独立预测因子。

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Expression of MASTL (Greatwall) associates with good prognosis and response to radiotherapy in pharyngeal squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) are highly heterogeneous in both disease progression and treatment outcome, with hardly any molecular biomarker in clinical practice. Thus, the aim of this study was to investigate the potential prognostic and predictive value of MASTL/Greatwall, a mitotic kinase also involved in PI3K-mTOR signaling and the DNA damage response, in HNSCC.

MASTL expression was evaluated by immunohistochemistry in a cohort of 346 surgically treated HPV-negative pharyngeal and laryngeal squamous cell carcinoma patients, as well as in pre-treatment biopsies from a separate cohort of 64 patients treated with induction chemotherapy (ICT). In addition, MASTL mRNA expression was analyzed in 135 patients from The Cancer Genome Atlas (TCGA) database.

High MASTL expression was significantly associated with improved disease-specific survival (DSS) (P = 0.029), specifically in well-differentiated pharyngeal squamous cell carcinoma (PSCC) tumors (P = 0.002). Notably, this association was restricted to patients who received adjuvant radiotherapy (RT) (P = 0.009). Consistently, a similar correlation was found at the mRNA level in PSCC tumors from the TCGA dataset. Moreover, the combined expression of MASTL and p21 was significantly associated with better DSS, specifically among patients receiving RT (P = 0.014). Multivariate Cox regression analysis further confirmed that high MASTL expression was independently associated with favorable prognosis in patients who received post-operative RT (HR= 0.65; 95 % CI: 0.45–0.94; P = 0.021).

Collectively, these findings unprecedentedly revealed the association between high MASTL expression and favorable outcome in advanced HPV-negative PSCC, in marked contrast to previous reports in other tumor types. Importantly, MASTL expression emerges as an independent predictor of good prognosis in RT-treated PSCC patients.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.