# Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma

**Authors:** Yuan Wang, Wei Su, Guangyao Zhou, Yijie Wang, Chunnuan Wu, Pengpeng Zhang, Lianmin Zhang

PMC · DOI: 10.1111/1759-7714.70140 · Thoracic Cancer · 2025-08-06

## TL;DR

Researchers used single-cell RNA data and machine learning to identify a gene signature linked to RNA modification ac4C in lung cancer, which could help predict patient outcomes and treatment responses.

## Contribution

A novel ac4C-related gene signature (ARGSig) was developed using machine learning for prognosis prediction in lung adenocarcinoma.

## Key findings

- Cells with high ac4C activity showed increased intercellular communication and tumor-associated pathway activation.
- The ARGSig model effectively stratified patients by survival outcomes and predicted treatment sensitivity.
- ac4C modification and its related genes are critical in lung adenocarcinoma development.

## Abstract

Lung adenocarcinoma, the most common subtype of non‐small cell lung cancer, faces challenges such as drug resistance and tumor heterogeneity. N4‐acetylcytidine (ac4C) is an important RNA modification involved in cancer progression, but its role in lung adenocarcinoma remains unclear.

This study analyzed transcriptomic and single‐cell RNA sequencing data from public databases to investigate the expression and clinical significance of ac4C‐related genes in lung adenocarcinoma. Ten machine learning algorithms were applied to develop and validate an ac4C‐related gene signature (ARGSig) for prognosis prediction across multiple independent cohorts.

Cells with high ac4C activity showed increased intercellular communication and activation of tumor‐associated pathways. The ARGSig model effectively stratified patients by survival outcomes and predicted sensitivity to immune checkpoint inhibitors and chemotherapy agents.

ac4C modification and its related genes play a critical role in lung adenocarcinoma development. The ARGSig model provides a promising molecular tool for prognosis evaluation and personalized treatment guidance in lung adenocarcinoma patients.

This study combines single‐cell RNA sequencing and bulk transcriptomics to investigate the role of ac4C RNA modification in lung adenocarcinoma. Using 10 machine learning algorithms, an ac4C‐related gene signature (ARGSig) was constructed and validated for prognosis prediction.

## Linked entities

- **Diseases:** lung adenocarcinoma (MONDO:0005061)

## Full-text entities

- **Diseases:** cancer (MESH:D009369), non-small cell lung cancer (MESH:D002289), Lung Adenocarcinoma (MESH:D000077192)
- **Chemicals:** N4-acetylcytidine (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12326626/full.md

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Source: https://tomesphere.com/paper/PMC12326626