Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers

Abstract Hepatocellular carcinoma and cholangiocarcinoma, the two predominant histological subtypes of primary liver cancer, are characterized by a high global incidence and poor prognosis. Moreover, the therapeutic options are still limited, with surgical intervention being the predominant approach...

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Main Authors: Yajing Zhu, Pan Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-96488-4
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author Yajing Zhu
Pan Zhang
author_facet Yajing Zhu
Pan Zhang
author_sort Yajing Zhu
collection DOAJ
description Abstract Hepatocellular carcinoma and cholangiocarcinoma, the two predominant histological subtypes of primary liver cancer, are characterized by a high global incidence and poor prognosis. Moreover, the therapeutic options are still limited, with surgical intervention being the predominant approach. Anchorage-Dependent Cell Death (Anoikis) is a form of regulated cell death triggered by the detachment of cells from their extracellular matrix, is crucial for maintaining tissue homeostasis. However, tumor cells often evade anoikis, a capability that is essential for their survival in the bloodstream and subsequent metastasis. Our study classified liver cancer into two distinct subtypes, C1 and C2, based on the differential expression of anoikis-related genes. Subtype C1 patients exhibited elevated expression of BRMS1, PTK2, and CASP8, which could serve as potential therapeutic targets for anoikis-based treatments. Conversely, subtype C2 patients showed higher expression of NTRK2, STAT3, SIK1, AKT1, and EGFR, suggesting these genes as promising therapeutic targets for C2 subtype liver cancer. Furthermore, employing Weighted Correlation Network analysis, machine learning models, and experimental validation, we identified NPY1R and HGF as potential biomarkers for the diagnosis and treatment of liver cancer.
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spelling doaj-art-2eb11ea9749c4f368f9ed01b1c1136cf2025-08-20T02:24:30ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-96488-4Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkersYajing Zhu0Pan Zhang1Department of Infectious Diseases, The Third Xiangya Hospital of Central South UniversityDepartment of Infectious Diseases, The Third Xiangya Hospital of Central South UniversityAbstract Hepatocellular carcinoma and cholangiocarcinoma, the two predominant histological subtypes of primary liver cancer, are characterized by a high global incidence and poor prognosis. Moreover, the therapeutic options are still limited, with surgical intervention being the predominant approach. Anchorage-Dependent Cell Death (Anoikis) is a form of regulated cell death triggered by the detachment of cells from their extracellular matrix, is crucial for maintaining tissue homeostasis. However, tumor cells often evade anoikis, a capability that is essential for their survival in the bloodstream and subsequent metastasis. Our study classified liver cancer into two distinct subtypes, C1 and C2, based on the differential expression of anoikis-related genes. Subtype C1 patients exhibited elevated expression of BRMS1, PTK2, and CASP8, which could serve as potential therapeutic targets for anoikis-based treatments. Conversely, subtype C2 patients showed higher expression of NTRK2, STAT3, SIK1, AKT1, and EGFR, suggesting these genes as promising therapeutic targets for C2 subtype liver cancer. Furthermore, employing Weighted Correlation Network analysis, machine learning models, and experimental validation, we identified NPY1R and HGF as potential biomarkers for the diagnosis and treatment of liver cancer.https://doi.org/10.1038/s41598-025-96488-4
spellingShingle Yajing Zhu
Pan Zhang
Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
Scientific Reports
title Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
title_full Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
title_fullStr Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
title_full_unstemmed Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
title_short Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
title_sort gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers
url https://doi.org/10.1038/s41598-025-96488-4
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AT panzhang geneexpressionprofileofanoikisrevealsnewsubtypesoflivercanceranddiscoveryoftherapeutictargetsandbiomarkers