# The multi-omics analysis identifies a novel endoplasmic reticulum stress and immune related genes signature in lung adenocarcinoma

## TL;DR

This study identifies a new gene signature related to endoplasmic reticulum stress and immune response in lung adenocarcinoma, which helps predict patient outcomes and treatment responses.

## Contribution

A novel ERS-immune gene signature is developed for LUAD prognosis and therapeutic insights.

## Key findings

- A 10-gene signature stratifies LUAD patients into distinct risk groups with significant survival differences.
- The nomogram integrating risk scores outperforms traditional staging systems in predictive accuracy.
- CR2 gene knockdown reduces cancer cell proliferation and metastasis.

## Abstract

Lung adenocarcinoma (LUAD), a prevalent and aggressive malignancy, necessitates improved prognostic tools and therapeutic insights. While endoplasmic reticulum stress (ERS) and tumor-immune interactions are recognized as key cancer hallmarks, their combined prognostic potential in LUAD remains insufficiently explored.

Utilizing transcriptomic and clinical data from the TCGA-LUAD cohort, we developed an ERS-immune prognostic signature through Least Absolute Shrinkage and Selection Operator algorithm. A clinical nomogram integrating risk scores with established prognostic factors was established. Tumor microenvironment characteristics were evaluated using the CIBERSORT and ESTIMATE algorithm. The changes following the CR2 gene knockdown in NSCLC cells were evaluated through CCK-8 assay and Transwell assays.

The 10-gene signature effectively stratified patients into distinct risk groups with significant survival differences. The nomogram demonstrated enhanced predictive accuracy compared to traditional staging systems. High-risk patients exhibited immunosuppressive features. CR2 knockdown significantly reduced cellular proliferation and inhibited metastatic capacity.

This integrated ERS-immune signature provides clinically relevant prognostic stratification and reveals potential therapeutic vulnerabilities in LUAD, offering a framework for personalized treatment strategies.

The online version contains supplementary material available at 10.1007/s12672-025-03033-w.