xCT as a Predictor for Survival in a Population-Based Cohort of Head and Neck Squamous Cell Carcinoma

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-11-02 DOI:10.1002/cam4.70371

Linda Nissi, Sanni Tuominen, Johannes Routila, Teemu Huusko, Petra Ketonen, Maria Sundvall, Ilmo Leivo, Heikki Irjala, Heikki Minn, Tove J. Grönroos, Sami Ventelä

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Abstract

Background

xCT, also known as SLC7A11 (solute carrier Family 7 Member 11), is a cystine/glutamate antiporter protein that mediates regulated cell death and antioxidant defense. The aim of this study was to investigate the effect of xCT on the outcome of patients diagnosed with new head and neck squamous cell carcinoma (HNSCC).

Methods

This retrospective cohort study utilized a population-based dataset, comprising all patients (n = 1033) diagnosed with new HNSCC during 2005–2015 in a population of 697,000 people. All patients (n = 585) with a tumor tissue sample available for immunohistochemical (IHC) staining were included. The follow-up rates were 97% and 81% at 3 and 5 years, respectively. Also, the specificity of the anti-xCT antibody was validated.

Results

The expression level and prognostic significance of xCT were strongly dependent on tumor location. In oropharyngeal squamous cell carcinoma (OPSCC) patients, xCT expression was a significant prognostic factor for 5-year overall survival (OAS) (HR: 2.71; 95% CI 1.67–4.39; p < 0.001), disease-specific survival (DSS) (HR: 2.58; 95% CI 1.47–4.54; p = 0.001), and disease-free survival (DFS) (HR: 2.69; 95% CI 1.55–4.64; p < 0.001). Five-year survival rates for OPSCC patients with high and low levels of xCT were OAS 34% versus 62%; DSS 51% versus 73%; DFS 43% versus 73%, respectively. According to a multivariate model adjusted for age, T-class, nodal positivity, and tobacco consumption, xCT was an independent prognostic factor for 3-year survival, in which it outperformed p16 IHC. Similar associations were not observed in squamous cell carcinomas of oral cavity or larynx. Regarding treatment modalities, xCT was most predictive in HNSCC patients who received radiotherapy.

Conclusions

High xCT expression was associated with poor prognosis in OPSCC. Our findings suggest that joint analysis of xCT and p16 may add significant value in OPSCC treatment stratification.

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xCT 作为头颈部鳞状细胞癌人群队列的生存预测指标。

背景：xCT又称SLC7A11（溶质运载家族7成员11），是一种胱氨酸/谷氨酸反转运蛋白，可介导调节细胞死亡和抗氧化防御。本研究旨在探讨 xCT 对新确诊头颈部鳞状细胞癌（HNSCC）患者预后的影响：这项回顾性队列研究利用了一个基于人口的数据集，其中包括2005-2015年期间在69.7万人口中诊断为新发HNSCC的所有患者（n = 1033）。所有肿瘤组织样本可用于免疫组化染色的患者（n = 585）均被纳入研究。3年和5年的随访率分别为97%和81%。此外，还验证了抗 xCT 抗体的特异性：结果：xCT的表达水平和预后意义与肿瘤位置密切相关。在口咽鳞癌（OPSCC）患者中，xCT表达是5年总生存率（OAS）的重要预后因素（HR：2.71；95% CI 1.67-4.39；P 结论：xCT高表达与患者的预后不良有关：xCT的高表达与OPSCC的不良预后有关。我们的研究结果表明，xCT和p16的联合分析可能会为OPSCC的治疗分层增加重要价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.