Prognostic significance of KIF2C and its association with lactate metabolism in hepatocellular carcinoma
Abstract
BackgroundHepatocellular carcinoma (HCC) remains a global health challenge with limited therapeutic options. Recent evidence suggests that protein lactylation, a novel post-translational modification (PTM) driven by lactate, plays a crucial role in tumor remodeling. However, the specific regulators mediating the lactylation landscape in HCC are not fully elucidated.MethodsWe integrated weighted gene co-expression network analysis (WGCNA) and analysis of differentially expressed genes (DEGs) to identify key lactylation-related genes in HCC. The clinical significance of kinesin family member 2C (KIF2C) was validated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Functional assays, including Cell Counting Kit-8 (CCK-8), wound-healing, and Transwell assays, were performed to evaluate the effects of KIF2C on HCC cell viability, migration. Lactate measurements and Western blot analyses were conducted to assess changes in lactate levels and metabolism-, apoptosis-, and epithelial–mesenchymal transition (EMT)-related protein expression following KIF2C manipulation.ResultsKIF2C was identified as a candidate hub gene, with consistent overexpression in HCC across multiple cohorts and validation experiments. High KIF2C expression was associated with poor prognosis. Functional assays in Huh7 cells suggested that KIF2C silencing reduced hexokinase 2 (HK2) expression and lactate abundance, whereas KIF2C overexpression was accompanied by opposite changes. These findings suggest a potential association between KIF2C expression and lactate-related metabolic alterations in HCC cells.ConclusionElevated KIF2C expression was associated with adverse clinical features and a lactate-related metabolic phenotype in HCC. Functional experiments were observed that KIF2C expression manipulation altered cellular lactate levels and metabolism-related protein expression. However, the underlying molecular mechanisms and potential involvement of protein lactylation remain to be investigated.
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BibTeX
@article{li2026prognostic,
title = {{Prognostic significance of KIF2C and its association with lactate metabolism in hepatocellular carcinoma}},
author = {Jiashuo Li and Haowen Liu and Liwei Shen and Lihua Zhang and Guangtan Du and Qianqian Liu and Boyu Qiu and Wensheng Qiu and Shasha Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1982838},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982838},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prognostic significance of KIF2C and its association with lactate metabolism in hepatocellular carcinoma
AU - Jiashuo Li
AU - Haowen Liu
AU - Liwei Shen
AU - Lihua Zhang
AU - Guangtan Du
AU - Qianqian Liu
AU - Boyu Qiu
AU - Wensheng Qiu
AU - Shasha Wang
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1982838
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982838
AB - BackgroundHepatocellular carcinoma (HCC) remains a global health challenge with limited therapeutic options. Recent evidence suggests that protein lactylation, a novel post-translational modification (PTM) driven by lactate, plays a crucial role in tumor remodeling. However, the specific regulators mediating the lactylation landscape in HCC are not fully elucidated.MethodsWe integrated weighted gene co-expression network analysis (WGCNA) and analysis of differentially expressed genes (DEGs) to identify key lactylation-related genes in HCC. The clinical significance of kinesin family member 2C (KIF2C) was validated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Functional assays, including Cell Counting Kit-8 (CCK-8), wound-healing, and Transwell assays, were performed to evaluate the effects of KIF2C on HCC cell viability, migration. Lactate measurements and Western blot analyses were conducted to assess changes in lactate levels and metabolism-, apoptosis-, and epithelial–mesenchymal transition (EMT)-related protein expression following KIF2C manipulation.ResultsKIF2C was identified as a candidate hub gene, with consistent overexpression in HCC across multiple cohorts and validation experiments. High KIF2C expression was associated with poor prognosis. Functional assays in Huh7 cells suggested that KIF2C silencing reduced hexokinase 2 (HK2) expression and lactate abundance, whereas KIF2C overexpression was accompanied by opposite changes. These findings suggest a potential association between KIF2C expression and lactate-related metabolic alterations in HCC cells.ConclusionElevated KIF2C expression was associated with adverse clinical features and a lactate-related metabolic phenotype in HCC. Functional experiments were observed that KIF2C expression manipulation altered cellular lactate levels and metabolism-related protein expression. However, the underlying molecular mechanisms and potential involvement of protein lactylation remain to be investigated.
SN - 1664-3224
ER -