# Identification of C1QA as a prognostic marker and regulator of immunosuppressive neutrophils in early-stage lung adenocarcinoma through integrated bioinformatics analyses

## TL;DR

This study identifies C1QA as a key gene linked to immunosuppressive neutrophils in early-stage lung cancer, suggesting it could be a new target for treatment.

## Contribution

The study introduces C1QA as a novel prognostic marker and regulator of immunosuppressive neutrophils in early-stage lung adenocarcinoma.

## Key findings

- High neutrophil scores are associated with poor prognosis in early-stage LUAD.
- C1QA is identified as the hub gene most correlated with neutrophil abundance.
- C1QA expression correlates with immunosuppressive markers IL-10 and TGFB1.

## Abstract

Neutrophils infiltrate lung tumours and can exhibit an immunosuppressive phenotype that promotes tumour growth, yet their regulation in early-stage lung cancer remains unclear. This study investigates molecular regulators of neutrophils in early-stage lung adenocarcinoma (LUAD) using publicly available gene expression datasets. An early-stage LUAD dataset (GSE31210) was analysed using CIBERSORTx to estimate neutrophil abundance. Weighted gene co-expression network analysis (WGCNA) identified the hub gene most correlated with neutrophil scores. Single-cell RNA sequencing (scRNA-seq) was used to determine the cellular source and regulatory mechanisms of this gene. A high neutrophil score was a negative prognostic factor, validated in independent datasets. WGCNA identified C1QA as the key gene linked to neutrophil abundance. scRNA-seq and immunofluorescence staining confirmed macrophages as the primary source of C1QA. Cell–cell communication analysis suggested C1QA interacts with neutrophils via complement receptors, contributing to an immunosuppressive tumour microenvironment. RT-qPCR showed C1QA expression correlated with IL-10 and TGFB1, markers of immunosuppression. C1QA is a poor prognostic marker in LUAD, potentially driving immunosuppressive tumour-associated neutrophils. Targeting C1QA and its pathway may offer a novel therapeutic strategy in early-stage LUAD.

The online version contains supplementary material available at 10.1007/s10238-025-01881-y.