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

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Neoadjuvant chemoimmunotherapy improves outcomes in non-small-cell lung cancer (NSCLC), but predicting patient response remains challenging.
• Identifying patients who will benefit most from this treatment is critical for optimizing therapeutic strategies.

Purpose of the Study:

• To identify predictive biomarkers for pathological response to neoadjuvant chemoimmunotherapy in NSCLC.
• To investigate the role of interferon signaling pathways and specific genes in predicting treatment efficacy.

Main Methods:

• Analysis of baseline transcriptomic data from 24 NSCLC patients treated with neoadjuvant chemoimmunotherapy.
• Identification and validation of the NeoIGS interferon signaling pathway signature.
• Screening of key genes within NeoIGS using ROC analysis and validation by immunohistochemistry in a separate cohort of 53 NSCLC patients.

Main Results:

• Higher interferon signaling pathway expression and CD8+ T-cell infiltration were observed in patients with major pathological response (MPR).
• The NeoIGS signature accurately predicted pathological response to neoadjuvant chemoimmunotherapy (AUC=0.926) and immunotherapy efficacy.
• The gene ATF3 was identified as a key predictor, outperforming PD-L1 in predicting pathological response in a clinical cohort, with a 90.0% MPR rate in the high-ATF3 expression group.

Conclusions:

• A subset of interferon signaling pathways, termed NeoIGS, is strongly associated with immunotherapy response in NSCLC.
• ATF3 is a critical gene within NeoIGS that serves as an accurate predictive biomarker for pathological remission in patients receiving neoadjuvant chemoimmunotherapy.