# Identification and histological validation of autophagy-related core genes ADRB2 and PLK2 in keloids, with integrated immune infiltration analysis

## TL;DR

This study identifies ADRB2 and PLK2 as key autophagy-related genes in keloids, linking them to immune changes and fibrosis, with potential for diagnosis and treatment.

## Contribution

The study introduces ADRB2 and PLK2 as novel autophagy-related biomarkers in keloids, validated through histology and immune infiltration analysis.

## Key findings

- ADRB2 and PLK2 show significantly higher expression in keloid tissues compared to normal skin.
- These genes are associated with fibrotic and autophagy markers in keloid fibroblasts.
- Autophagy modulation affects ADRB2 but not PLK2 expression in keloid cells.

## Abstract

Keloids are pathological fibroproliferative scars characterized by excessive collagen deposition and a lack of effective targeted therapies. Autophagy dysregulation has been linked to keloid pathogenesis, but the underlying molecular mechanisms remain unclear.

Transcriptomic datasets were integrated and analyzed using differential expression analysis and weighted gene co-expression network analysis. Three machine learning algorithms—least absolute shrinkage and selection operator (LASSO), support vector machine–recursive feature elimination (SVM-RFE), and random forest—were applied to identify autophagy-related hub gene candidates in keloids. Immune infiltration and functional analyses were conducted to explore immune microenvironment alterations. Histological staining (H&E and Masson), immunohistochemistry, and Western blotting were used for tissue-level validation, while cellular experiments were performed in keloid fibroblasts with autophagy modulation.

ADRB2 and PLK2 were consistently identified as key autophagy-related candidate genes. Immune-related analyses suggested that these genes may be involved in remodeling the keloid immune microenvironment by influencing the abundance and functional status of multiple immune cell subsets. Histological and protein-level assays demonstrated significantly higher expression of ADRB2 and PLK2 in keloid tissues compared with adjacent normal skin. In keloid fibroblasts, fibrotic markers (COL1/COL3) and autophagy-related markers (LC3-II/LC3-I and p62) were upregulated concomitantly with ADRB2 and PLK2 at baseline. Autophagy modulation altered ADRB2 expression (decreased with EBSS and increased with chloroquine), whereas PLK2 expression remained largely unchanged.

These findings identify ADRB2 and PLK2 as under-recognized autophagy- andimmunity-related candidate biomarkers in keloids, highlighting their potential relevance asdiagnostic indicators and future therapeutic research targets.