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

ABSTRACT Introduction 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 un...

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Main Authors: Yuan Wang, Wei Su, Guangyao Zhou, Yijie Wang, Chunnuan Wu, Pengpeng Zhang, Lianmin Zhang
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.70140
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author Yuan Wang
Wei Su
Guangyao Zhou
Yijie Wang
Chunnuan Wu
Pengpeng Zhang
Lianmin Zhang
author_facet Yuan Wang
Wei Su
Guangyao Zhou
Yijie Wang
Chunnuan Wu
Pengpeng Zhang
Lianmin Zhang
author_sort Yuan Wang
collection DOAJ
description ABSTRACT Introduction 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. Methods 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. Results 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. Conclusion 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.
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institution Kabale University
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series Thoracic Cancer
spelling doaj-art-9c6fc797c88f46609cb12415bb8db9002025-08-20T04:01:02ZengWileyThoracic Cancer1759-77061759-77142025-08-011615n/an/a10.1111/1759-7714.70140Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung AdenocarcinomaYuan Wang0Wei Su1Guangyao Zhou2Yijie Wang3Chunnuan Wu4Pengpeng Zhang5Lianmin Zhang6Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer Tianjin ChinaDepartment of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital Tianjin ChinaDepartment of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital Tianjin ChinaDepartment of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital Tianjin ChinaKey Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer Tianjin ChinaDepartment of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital Tianjin ChinaDepartment of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital Tianjin ChinaABSTRACT Introduction 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1111/1759-7714.70140lung cancermachine learningN4‐acetylcytidineprognostic signatureRNA modification
spellingShingle Yuan Wang
Wei Su
Guangyao Zhou
Yijie Wang
Chunnuan Wu
Pengpeng Zhang
Lianmin Zhang
Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma
Thoracic Cancer
lung cancer
machine learning
N4‐acetylcytidine
prognostic signature
RNA modification
title Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma
title_full Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma
title_fullStr Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma
title_full_unstemmed Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma
title_short Integrating Single‐Cell Transcriptomics and Machine Learning to Define an ac4C Gene Signature in Lung Adenocarcinoma
title_sort integrating single cell transcriptomics and machine learning to define an ac4c gene signature in lung adenocarcinoma
topic lung cancer
machine learning
N4‐acetylcytidine
prognostic signature
RNA modification
url https://doi.org/10.1111/1759-7714.70140
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