# Histone demethylase JMJD2D emerges as a novel prognostic biomarker and exhibits correlation with immune infiltration in lung adenocarcinoma

## TL;DR

This study finds that high levels of the protein JMJD2D in lung adenocarcinoma are linked to worse survival and immune system changes, suggesting it could be a useful biomarker for diagnosis and treatment.

## Contribution

The study identifies JMJD2D as a novel prognostic biomarker in lung adenocarcinoma and explores its correlation with immune infiltration and drug response.

## Key findings

- High JMJD2D expression in lung adenocarcinoma is associated with poor survival outcomes and advanced tumor stages.
- High JMJD2D levels correlate with decreased immune-related processes and increased Tregs and CD40 expression.
- JMJD2D is linked to resistance to certain drugs but sensitivity to others, and a prognostic signature of eight related genes was identified.

## Abstract

Lysine demethylase 4D (KDM4D or JMJD2D) plays a significant role in tumorigenesis, development, and poor clinical outcomes. However, its roles in lung adenocarcinoma (LUAD) remains unclear. This study aimed to identify the role and molecular mechanisms of JMJD2D in LUAD.

The study investigated the correlation of JMJD2D with tumor development, immune cell infiltration, response to antitumor therapy, tumor mutation burden and prognostic values.

JMJD2D had high expression in LUAD. High-JMJD2D expression was associated with poor survival outcomes and the T stage of LUAD patients. Furthermore, high-JMJD2D expression was linked to the decreased immune-related processes, associated with the increased Tregs and CD40 expression. Additionally, high-JMJD2D expression was associated with frequent alterations with higher TMB and resistance to BMS.708,163, Roscovitine, and Pyrimethamine, but sensitivities to ATRA, Bosutinib, and JNK. Inhibitor. VIII. Moreover, the study identified eight JMJD2D-related genes as a prognostic signature and constructed a predictive nomogram based on independent prognostic factors.

JMJD2D acts as an oncogene in LUAD and is involved in tumorigenesis, development, and poor clinical outcomes. Therefore, JMJD2D may serve as a potential prognostic biomarker in diagnosis and treatment of LUAD. The study emphasizes the importance of the molecular mechanisms of JMJD2D in LUAD.

The online version contains supplementary material available at 10.1007/s12672-025-02871-y.