Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma

Abstract Background Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenv...

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Main Authors: Fushan Gao, Wenlin Gong, Haihua He, Zhen Zhang, Hongcai Yang, Fei Shao, Yibo Gao, Jie He
Format: Article
Language:English
Published: Springer 2024-12-01
Series:Cancer Immunology, Immunotherapy
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Online Access:https://doi.org/10.1007/s00262-024-03870-8
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author Fushan Gao
Wenlin Gong
Haihua He
Zhen Zhang
Hongcai Yang
Fei Shao
Yibo Gao
Jie He
author_facet Fushan Gao
Wenlin Gong
Haihua He
Zhen Zhang
Hongcai Yang
Fei Shao
Yibo Gao
Jie He
author_sort Fushan Gao
collection DOAJ
description Abstract Background Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenvironment are not fully understood. This study investigated the impact of HNF1B on colon cancer immunotherapy in depth. Methods We analyzed 1,374 colon adenocarcinoma samples from the TCGA and GEO datasets. Our approach involved bioinformatics to uncover how HNF1B influences immunotherapy and the immune microenvironment, with corroboration from external databases and experimental validation. Results HNF1B was expressed at low levels in colon adenocarcinoma and was linked to patient prognosis. CIBERSORT, TIME, and GSVA analyses revealed that HNF1B was associated with macrophage infiltration, immune checkpoints, and signaling pathways. Drug prediction suggested a negative relationship between HNF1B and EGFR-targeted therapies, implying potential resistance. Validation with external cohorts confirmed that patients with low HNF1B expression experienced less benefit from immunotherapy. Conclusion This study clarifies the role of HNF1B in the treatment of colon adenocarcinoma. This study provides a foundation for further in-depth mechanistic studies and proposes new directions for optimizing immunotherapy strategies for colon adenocarcinoma.
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spelling doaj-art-f3ada5553213484ba9a000bc69632c9e2025-02-02T12:26:38ZengSpringerCancer Immunology, Immunotherapy1432-08512024-12-0174111710.1007/s00262-024-03870-8Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinomaFushan Gao0Wenlin Gong1Haihua He2Zhen Zhang3Hongcai Yang4Fei Shao5Yibo Gao6Jie He7Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenvironment are not fully understood. This study investigated the impact of HNF1B on colon cancer immunotherapy in depth. Methods We analyzed 1,374 colon adenocarcinoma samples from the TCGA and GEO datasets. Our approach involved bioinformatics to uncover how HNF1B influences immunotherapy and the immune microenvironment, with corroboration from external databases and experimental validation. Results HNF1B was expressed at low levels in colon adenocarcinoma and was linked to patient prognosis. CIBERSORT, TIME, and GSVA analyses revealed that HNF1B was associated with macrophage infiltration, immune checkpoints, and signaling pathways. Drug prediction suggested a negative relationship between HNF1B and EGFR-targeted therapies, implying potential resistance. Validation with external cohorts confirmed that patients with low HNF1B expression experienced less benefit from immunotherapy. Conclusion This study clarifies the role of HNF1B in the treatment of colon adenocarcinoma. This study provides a foundation for further in-depth mechanistic studies and proposes new directions for optimizing immunotherapy strategies for colon adenocarcinoma.https://doi.org/10.1007/s00262-024-03870-8Colorectal adenocarcinomaImmunotherapyHepatocyte nuclear factor-1βTumor microenvironmentImmune checkpoint blockade
spellingShingle Fushan Gao
Wenlin Gong
Haihua He
Zhen Zhang
Hongcai Yang
Fei Shao
Yibo Gao
Jie He
Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma
Cancer Immunology, Immunotherapy
Colorectal adenocarcinoma
Immunotherapy
Hepatocyte nuclear factor-1β
Tumor microenvironment
Immune checkpoint blockade
title Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma
title_full Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma
title_fullStr Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma
title_full_unstemmed Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma
title_short Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma
title_sort integrated multi omics analysis reveals clinical significance of hepatocyte nuclear factor 1β in tumor immune microenvironment immunotherapy and prognostic prediction for colon adenocarcinoma
topic Colorectal adenocarcinoma
Immunotherapy
Hepatocyte nuclear factor-1β
Tumor microenvironment
Immune checkpoint blockade
url https://doi.org/10.1007/s00262-024-03870-8
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