A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC

Niemann-Pick type C1 protein (NPC1), a key regulator of intracellular cholesterol transport and a transmembrane protein, has been implicated in carcinogenesis, particularly in hepatocellular carcinoma (HCC). Despite the noted association, the specific role of NPC1 in HCC remains underexplored. In th...

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Main Authors: Xingjun Lu, Tianyao Gou, Xuxing He, Xia Chen, Daqing Yang, Xiaozhen Peng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1588583/full
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author Xingjun Lu
Tianyao Gou
Xuxing He
Xia Chen
Daqing Yang
Xiaozhen Peng
Xiaozhen Peng
author_facet Xingjun Lu
Tianyao Gou
Xuxing He
Xia Chen
Daqing Yang
Xiaozhen Peng
Xiaozhen Peng
author_sort Xingjun Lu
collection DOAJ
description Niemann-Pick type C1 protein (NPC1), a key regulator of intracellular cholesterol transport and a transmembrane protein, has been implicated in carcinogenesis, particularly in hepatocellular carcinoma (HCC). Despite the noted association, the specific role of NPC1 in HCC remains underexplored. In this study, we conducted a comprehensive analysis of NPC1 expression across diverse gene expression databases to elucidate its prognostic significance and functional interactions. Utilizing LinkedOmics for co-expression network analysis and KEGG for functional enrichment, we identified a set of genes co-expressed with NPC1 and its associated biological pathways. Our findings demonstrate that NPC1 is frequently upregulated and amplified in HCC tumor tissues, with higher expression levels significantly associated with reduced overall survival (OS), progression-free survival (RFS), and disease-free survival (DFS). Functional enrichment analysis of the top 50 positively correlated genes with NPC1 highlighted significant enrichment in pathways related to organelle fission, nuclear division, chromosomal region spindle formation, and centrosome function, suggesting a role for NPC1 in DNA replication processes. These findings establish a correlation between NPC1 expression and HCC prognosis, laying the groundwork for future studies to explore the therapeutic potential of NPC1 inhibition in HCC.
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publishDate 2025-08-01
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spelling doaj-art-e5c8f52d62264a9b8eab15d0d14277b92025-08-20T03:37:31ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-08-011610.3389/fgene.2025.15885831588583A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCCXingjun Lu0Tianyao Gou1Xuxing He2Xia Chen3Daqing Yang4Xiaozhen Peng5Xiaozhen Peng6College of Laboratory Medicine, Hunan University of Medicine, Huaihua, ChinaXiangya Second Hospital, Central South University, Changsha, ChinaClinical Medicine Department, Xinjiang Medical University, Urumqi, ChinaDepartment of Neurology, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, ChinaCollege of Laboratory Medicine, Hunan University of Medicine, Huaihua, ChinaCollege of Laboratory Medicine, Hunan University of Medicine, Huaihua, ChinaHunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, ChinaNiemann-Pick type C1 protein (NPC1), a key regulator of intracellular cholesterol transport and a transmembrane protein, has been implicated in carcinogenesis, particularly in hepatocellular carcinoma (HCC). Despite the noted association, the specific role of NPC1 in HCC remains underexplored. In this study, we conducted a comprehensive analysis of NPC1 expression across diverse gene expression databases to elucidate its prognostic significance and functional interactions. Utilizing LinkedOmics for co-expression network analysis and KEGG for functional enrichment, we identified a set of genes co-expressed with NPC1 and its associated biological pathways. Our findings demonstrate that NPC1 is frequently upregulated and amplified in HCC tumor tissues, with higher expression levels significantly associated with reduced overall survival (OS), progression-free survival (RFS), and disease-free survival (DFS). Functional enrichment analysis of the top 50 positively correlated genes with NPC1 highlighted significant enrichment in pathways related to organelle fission, nuclear division, chromosomal region spindle formation, and centrosome function, suggesting a role for NPC1 in DNA replication processes. These findings establish a correlation between NPC1 expression and HCC prognosis, laying the groundwork for future studies to explore the therapeutic potential of NPC1 inhibition in HCC.https://www.frontiersin.org/articles/10.3389/fgene.2025.1588583/fullNPC1prognosisbiomarkerHCCtherapeutic target
spellingShingle Xingjun Lu
Tianyao Gou
Xuxing He
Xia Chen
Daqing Yang
Xiaozhen Peng
Xiaozhen Peng
A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC
Frontiers in Genetics
NPC1
prognosis
biomarker
HCC
therapeutic target
title A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC
title_full A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC
title_fullStr A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC
title_full_unstemmed A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC
title_short A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC
title_sort comprehensive analysis identifies and validates npc1 as a potential biomarker for prognosis in hcc
topic NPC1
prognosis
biomarker
HCC
therapeutic target
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1588583/full
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