ERO1A作为早期肺腺癌风险分层和免疫治疗指导的新型生物标志物
ERO1A as a novel biomarker for risk stratification and immunotherapeutic guidance in early-stage lung adenocarcinoma.
摘要(中文译文)
相当比例的早期肺腺癌（esLUAD）患者在根治性切除术后出现复发，凸显了改进生物标志物的必要性。现有生物标志物如PD-L1和肿瘤突变负荷（TMB）在早期疾病中的预测效用有限。通过无偏筛选方法，内质网氧化还原酶1α（ERO1A）被鉴定为有待进一步研究的候选基因。整合了来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的多组学数据。采用机器学习算法（最小绝对收缩和选择算子（LASSO）、随机森林（RF）、支持向量机（SVM））识别核心预后基因。进行了功能富集、免疫微环境分析和药物敏感性预测。关键发现通过免疫组织化学（IHC）在独立机构队列中进行了验证。ERO1A被鉴定为esLUAD总生存期和无复发生存期不良的稳健、独立预测因子。其在肿瘤中显著上调，并与增殖通路增强相关。矛盾的是，高ERO1A表达与免疫激活的肿瘤微环境相关，其特征为CD8+ T细胞浸润丰富、M2巨噬细胞减少以及成熟三级淋巴结构增多。ERO1A高表达肿瘤表现出TMB和PD-L1水平升高，并在验证队列中与免疫检查点抑制剂更优的应答相关。生物信息学分析提示，ERO1A高表达肿瘤可能对传统化疗表现出耐药性，同时对表皮生长因子受体（EGFR）靶向治疗显示潜在敏感性，但此点未在临床验证中得到确认。ERO1A表达将肺腺癌（LUAD）分层为具有不同治疗意义的亚群。它代表了用于预后分层和免疫治疗选择的有前景的生物标志物，支持其在指导围手术期治疗决策中的潜在临床效用。
Abstract
A considerable proportion of patients with early-stage lung adenocarcinoma (esLUAD) experience recurrence after curative resection, highlighting the need for improved biomarkers. Current biomarkers such as PD-L1 and tumor mutational burden (TMB) have limited predictive utility in early-stage disease. Through an unbiased screening approach, endoplasmic reticulum oxidoreductase 1α (ERO1A) was identified as a candidate gene for further investigation. Multi-omics data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were integrated. Machine learning algorithms (least absolute shrinkage and selection operator (LASSO), random forest (RF), support vector machine (SVM)) were employed to identify core prognostic genes. Functional enrichment, immune microenvironment analysis, and drug sensitivity prediction were conducted. Key findings were validated using immunohistochemistry (IHC) in an independent institutional cohort. ERO1A was identified as a robust, independent predictor of poor overall and recurrence-free survival in esLUAD. It was significantly upregulated in tumors and associated with enhanced proliferative pathways. Paradoxically, high ERO1A expression correlated with an immune-activated tumor microenvironment, characterized by enriched CD8 + T cell infiltration, reduced M2 macrophages, and increased mature tertiary lymphoid structures. ERO1A-high tumors exhibited elevated TMB and PD-L1 levels, and were associated with superior response to immune checkpoint inhibitors in validation cohorts. Bioinformatic analysis suggested that ERO1A-high tumors might exhibit resistance to conventional chemotherapy while showing potential sensitivity to epidermal growth factor receptor (EGFR)-targeted therapies, though this was not confirmed in clinical validation. ERO1A expression stratifies lung adenocarcinoma (LUAD) into distinct subsets with divergent therapeutic implications. It represents a promising biomarker for prognostic stratification and immunotherapy selection, supporting its potential clinical utility in guiding peri-operative therapy decisions.
如何引用
AMA
Wangyu Chen, Haiming Li, Jie Zeng, Guijing Xie, Zhibo Chen, Xie Xu, et al. ERO1A as a novel biomarker for risk stratification and immunotherapeutic guidance in early-stage lung adenocarcinoma.. PeerJ. 2026; doi:10.7717/peerj.21347.
APA
Wangyu Chen, Haiming Li, Jie Zeng, Guijing Xie, Zhibo Chen, Xie Xu, et al (2026). ERO1A as a novel biomarker for risk stratification and immunotherapeutic guidance in early-stage lung adenocarcinoma.. PeerJ. https://doi.org/10.7717/peerj.21347
GB/T 7714
Wangyu Chen, Haiming Li, Jie Zeng, Guijing Xie, Zhibo Chen, Xie Xu, et al. ERO1A as a novel biomarker for risk stratification and immunotherapeutic guidance in early-stage lung adenocarcinoma.[J]. PeerJ, 2026 doi:10.7717/peerj.21347.
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