The role of JPT1 in hepatocellular carcinoma: tumor progression, microtubule dynamics regulation, and potential mechanisms within the immune microenvironment.

Abstract

Background: Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy worldwide, with its progression and metastasis significantly impacting patient prognosis. JPT1 (Jupiter microtubule-associated homolog 1), a novel microtubule-associated protein, has been implicated in regulating cytoskeletal stability, microtubule dynamics, and the immune microenvironment, thereby potentially driving HCC development and progression. However, the precise role and underlying mechanisms of JPT1 in HCC remain poorly understood.

Methods: This study integrated data from TCGA-LIHC and GEO (GSE14520) databases to systematically investigate the expression profile of JPT1 and its association with clinicopathological features and prognosis in HCC patients. A pan-cancer analysis was performed to evaluate JPT1 expression patterns and prognostic value across multiple cancer types. Differentially expressed gene (DEG) analysis, functional enrichment analysis (GSEA and KEGG), and spatial transcriptomics were utilized to explore the biological functions and mechanisms of JPT1 in tumor biology. Kaplan-Meier survival analysis and Cox proportional hazard models were employed to assess the prognostic potential of JPT1, while a nomogram was constructed to predict 1-, 3-, and 5-year survival rates in HCC patients.

Results: JPT1 was significantly overexpressed in HCC tissues, and high JPT1 expression was strongly associated with poor prognosis. The ROC analysis demonstrated that JPT1 expression had high diagnostic accuracy for HCC, with AUC values of 0.931 and 0.948 in the TCGA and GEO cohorts, respectively. Functional enrichment analysis revealed that JPT1-associated genes were enriched in pathways related to cell cycle regulation, DNA replication, and organic acid metabolism. GSVA further indicated that the high JPT1 expression group was significantly enriched in hallmark pathways such as hypoxia response, hormone response, and KRAS signaling. Spatial transcriptomics analysis showed that JPT1 was predominantly localized in low malignancy tumor regions and positively correlated with immune cells, including CD4 + T cells, CD8 + T cells, and macrophages. Additionally, high JPT1 expression was associated with an increased mutation frequency of TP53 and CTNNB1.

Conclusions: JPT1 plays a pivotal role in HCC progression, with its overexpression strongly linked to tumor advancement and poor prognosis. JPT1 likely contributes to the malignant evolution of HCC by modulating tumor metabolism, cell cycle regulation, and the immune microenvironment. This study provides a comprehensive insight into the role of JPT1 in HCC and establishes a theoretical foundation for its potential as a molecular biomarker and therapeutic target.