Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics

Gastric cancer is characterized by high heterogeneity, with its complex microenvironment and intercellular communications playing critical roles in disease progression and treatment responses. In this study, we utilized single-cell sequencing to dissect the intricate landscape of gastric cancer, ide...

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Main Authors: You Hu, Jun Xu, Jian Lv, Yan Qin, Yongda Lu, Fan Cen, Hongbao Yang, Kai Chen, Suhua Xia
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325000014
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author You Hu
Jun Xu
Jian Lv
Yan Qin
Yongda Lu
Fan Cen
Hongbao Yang
Kai Chen
Suhua Xia
author_facet You Hu
Jun Xu
Jian Lv
Yan Qin
Yongda Lu
Fan Cen
Hongbao Yang
Kai Chen
Suhua Xia
author_sort You Hu
collection DOAJ
description Gastric cancer is characterized by high heterogeneity, with its complex microenvironment and intercellular communications playing critical roles in disease progression and treatment responses. In this study, we utilized single-cell sequencing to dissect the intricate landscape of gastric cancer, identifying diverse cell populations and their interactions. We focused on the role of β-hydroxybutyrylation (Kbhb)-associated genes and their impact on the tumor microenvironment. By analyzing 189,700 single-cell profiles, we identified four distinct malignant epithelial cell subpopulations characterized by unique gene expression patterns. Among these, 20 β-hydroxybutyrylation (Kbhb)-associated genes were identified, including key genes such as MRPL13, LDHB, COX6C, FABP5, and RPS13, which were significantly associated with immune infiltration and tumor microenvironment remodeling. Hierarchical clustering based on these genes classified gastric cancer patients into two subgroups with distinct prognostic outcomes. Patients in the high-risk subgroup exhibited increased expression of pro-tumor genes and reduced immune infiltration, correlating with poorer survival. We further constructed a robust risk scoring model incorporating these genes, achieving AUC values of 0.72, 0.69, and 0.66 for predicting 1-, 3-, and 5-year survival in the TCGA dataset. These findings underscore the prognostic value of Kbhb-associated genes and their potential as therapeutic targets. This study not only provides insights into the molecular underpinnings of gastric cancer but also offers potential biomarkers for patient stratification and targets for therapeutic intervention.
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spelling doaj-art-6be5f55af27e466c91aeb2a6c91fa9322025-01-31T05:11:13ZengElsevierTranslational Oncology1936-52332025-03-0153102270Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristicsYou Hu0Jun Xu1Jian Lv2Yan Qin3Yongda Lu4Fan Cen5Hongbao Yang6Kai Chen7Suhua Xia8Department of General Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, PR ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, PR ChinaDepartment of Thoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, 200003 Shanghai, PR ChinaDepartment of Pathology, the Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi, 214122, Jiangsu, PR ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, PR ChinaDepartment of Oncology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, PR ChinaDepartment of Basic Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, PR ChinaDepartment of Oncology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, PR China; Corresponding authors.Department of Oncology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, PR China; Corresponding authors.Gastric cancer is characterized by high heterogeneity, with its complex microenvironment and intercellular communications playing critical roles in disease progression and treatment responses. In this study, we utilized single-cell sequencing to dissect the intricate landscape of gastric cancer, identifying diverse cell populations and their interactions. We focused on the role of β-hydroxybutyrylation (Kbhb)-associated genes and their impact on the tumor microenvironment. By analyzing 189,700 single-cell profiles, we identified four distinct malignant epithelial cell subpopulations characterized by unique gene expression patterns. Among these, 20 β-hydroxybutyrylation (Kbhb)-associated genes were identified, including key genes such as MRPL13, LDHB, COX6C, FABP5, and RPS13, which were significantly associated with immune infiltration and tumor microenvironment remodeling. Hierarchical clustering based on these genes classified gastric cancer patients into two subgroups with distinct prognostic outcomes. Patients in the high-risk subgroup exhibited increased expression of pro-tumor genes and reduced immune infiltration, correlating with poorer survival. We further constructed a robust risk scoring model incorporating these genes, achieving AUC values of 0.72, 0.69, and 0.66 for predicting 1-, 3-, and 5-year survival in the TCGA dataset. These findings underscore the prognostic value of Kbhb-associated genes and their potential as therapeutic targets. This study not only provides insights into the molecular underpinnings of gastric cancer but also offers potential biomarkers for patient stratification and targets for therapeutic intervention.http://www.sciencedirect.com/science/article/pii/S1936523325000014Gastric cancerSingle-cell analysisβ-HydroxybutyrylationImmune infiltrationCellular heterogeneity
spellingShingle You Hu
Jun Xu
Jian Lv
Yan Qin
Yongda Lu
Fan Cen
Hongbao Yang
Kai Chen
Suhua Xia
Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics
Translational Oncology
Gastric cancer
Single-cell analysis
β-Hydroxybutyrylation
Immune infiltration
Cellular heterogeneity
title Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics
title_full Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics
title_fullStr Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics
title_full_unstemmed Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics
title_short Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics
title_sort cellular heterogeneity and communication networks in gastric cancer single cell analysis reveals β hydroxybutyrylation associated genes and immune infiltration characteristics
topic Gastric cancer
Single-cell analysis
β-Hydroxybutyrylation
Immune infiltration
Cellular heterogeneity
url http://www.sciencedirect.com/science/article/pii/S1936523325000014
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