ATF3 Within the Interferon Signaling Pathway: A Potential Biomarker for Predicting Pathological Response to Neoadjuvant Chemoimmunotherapy.

IF 2.3 3区医学 Q3 ONCOLOGY

Thoracic Cancer Pub Date : 2025-04-01 DOI:10.1111/1759-7714.70056

Chao He, Rui Han, Taiming Zhang, Peng Zhong, Daijuan Huang, Conghua Lu, Yimin Zhang, Jianghua Li, Yuwen Deng, Yong He

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引用次数: 0

Abstract

Background: Neoadjuvant chemoimmunotherapy has achieved high downstaging and pathologic response rates in nonsmall-cell lung cancer (NSCLC), but outcomes vary significantly. Early identification of beneficiaries remains a challenge.

Methods: This study analyzed baseline transcriptomic data from 24 NSCLC patients (9 major pathological response [MPR], 15 nonmajor pathological response [NMPR]) treated with neoadjuvant chemoimmunotherapy, sourced from the GEO database. Molecular analyses and immune infiltration analyses were performed using pathologic response as an endpoint. After identifying the interferon signaling subset NeoIGS, we analyzed the relationship between NeoIGS and immune scores, immune cell infiltration, and immunotherapy efficacy. A key gene in NeoIGS was screened by reveiver operating characteristic curve (ROC) analysis. Subsequently, the expression of the key gene was assessed by immunohistochemistry in 53 NSCLC patients receiving neoadjuvant chemoimmunotherapy.

Results: Interferon signaling pathway expression and CD8+ T-cell infiltration were higher in the MPR group. NeoIGS predicted pathological response to neoadjuvant chemoimmunotherapy (AUC = 0.926) and also demonstrated predictive value in the ICIs monotherapy cohort. IPS and TIDE scores also confirmed NeoIGS's association with immunotherapy in the TCGA NSCLC dataset. Furthermore, patients with higher NeoIGS scores had more immune cell infiltration and increased expression of ICI targets. ROC analysis identified ATF3 as NeoIGS's key gene. In the clinical cohort, ATF3 outperformed PD-L1 in predicting pathologic response, with a 90.0% MPR rate in the high-expression group.

Conclusion: We established that a subset of interferon signaling pathways, NeoIGS, is closely associated with immunotherapy. Among them, ATF3 is the most critical gene that accurately predicts pathological remission in neoadjuvant chemoimmunotherapy.

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干扰素信号通路中的ATF3：预测新辅助化疗免疫治疗病理反应的潜在生物标志物。

背景：新辅助化疗免疫治疗在非小细胞肺癌（NSCLC）中取得了很高的降期率和病理反应率，但结果差异很大。早期确定受益人仍然是一项挑战。方法：本研究分析了24例接受新辅助化疗免疫治疗的NSCLC患者（9例主要病理反应[MPR]， 15例非主要病理反应[NMPR]）的基线转录组学数据，这些数据来自GEO数据库。以病理反应为终点进行分子分析和免疫浸润分析。在确定干扰素信号亚群NeoIGS后，我们分析了NeoIGS与免疫评分、免疫细胞浸润和免疫治疗疗效之间的关系。通过受试者工作特征曲线（ROC）分析筛选NeoIGS的关键基因。随后，采用免疫组化方法对53例接受新辅助化疗免疫治疗的NSCLC患者进行了关键基因的表达评估。结果：MPR组干扰素信号通路的表达和CD8+ t细胞的浸润均升高。NeoIGS预测新辅助化疗免疫治疗的病理反应（AUC = 0.926），并且在ICIs单药治疗队列中也显示出预测价值。IPS和TIDE评分也证实了TCGA NSCLC数据集中NeoIGS与免疫治疗的相关性。此外，NeoIGS评分越高的患者免疫细胞浸润越多，ICI靶点表达增加。ROC分析鉴定ATF3为NeoIGS的关键基因。在临床队列中，ATF3在预测病理反应方面优于PD-L1，高表达组的MPR率为90.0%。结论：我们确定干扰素信号通路的一个子集NeoIGS与免疫治疗密切相关。其中，ATF3是准确预测新辅助化疗免疫治疗病理缓解的最关键基因。

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

Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM

CiteScore

5.20

自引率

3.40%

发文量

439

审稿时长

2 months

期刊介绍： Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.