# Clinical significance and biological function of interferon regulatory factor 1 in non-small cell lung cancer

## TL;DR

This study explores how interferon regulatory factor 1 (IRF1) affects treatment outcomes and survival in non-small cell lung cancer patients receiving chemoimmunotherapy.

## Contribution

The study identifies IRF1 as a potential biomarker for predicting treatment response and prognosis in NSCLC through its regulation of the IL-2 pathway.

## Key findings

- High IRF1 levels correlate with longer progression-free survival in NSCLC patients undergoing chemoimmunotherapy.
- IRF1 is closely associated with immune regulatory factors like IL-2 and interferon pathways.
- IRF1 knockdown in animal models reduces its biological function, highlighting its role in vivo.

## Abstract

The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.