xCT 作为头颈鳞状细胞癌人群队列中生存的预测因子。

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

机构信息

Department of Oncology, and FICAN West Cancer Centre, Turku University Hospital and University of Turku, Turku, Finland.

Preclinical Imaging Turku PET Centre, University of Turku, Turku, Finland.

出版信息

Cancer Med. 2024 Nov;13(21):e70371. doi: 10.1002/cam4.70371.

DOI:10.1002/cam4.70371

PMID:39487701

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11530867/

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.

摘要

背景

xCT，也称为 SLC7A11（溶质载体家族 7 成员 11），是一种胱氨酸/谷氨酸反向转运蛋白，可介导细胞的调节性死亡和抗氧化防御。本研究旨在探讨 xCT 对新诊断的头颈部鳞状细胞癌（HNSCC）患者预后的影响。

方法

本回顾性队列研究利用了一个基于人群的数据集，该数据集包括 2005 年至 2015 年期间在 697000 人群中诊断为新的 HNSCC 的所有患者（n=1033）。所有有肿瘤组织样本可进行免疫组织化学（IHC）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强烈依赖于肿瘤位置。在口咽鳞状细胞癌（OPSCC）患者中，xCT 表达是 5 年总生存率（OAS）（HR：2.71；95%CI 1.67-4.39；p<0.001）、疾病特异性生存率（DSS）（HR：2.58；95%CI 1.47-4.54；p=0.001）和无病生存率（DFS）（HR：2.69；95%CI 1.55-4.64；p<0.001）的显著预后因素。xCT 高表达和低表达的 OPSCC 患者的 5 年生存率分别为 OAS 34% vs. 62%；DSS 51% vs. 73%；DFS 43% vs. 73%。根据调整年龄、T 分期、淋巴结阳性和吸烟状况的多变量模型，xCT 是 3 年生存率的独立预后因素，其预测能力优于 p16 IHC。在口腔或喉的鳞状细胞癌中未观察到类似的关联。关于治疗方式，xCT 在接受放疗的 HNSCC 患者中最具预测性。