Analysis of HKDC1 expression in multiple myeloma: a combined bioinformatic and experimental approach
DOI:
https://doi.org/10.63719/imrj.2026.12.02.004Keywords:
HKDC1, multiple myeloma, bioinformatic, transcriptomic, RT-qPCRAbstract
Hexokinase domain-containing 1 (HKDC1) has been recognised as a crucial protein involved in cancer metabolism. However, its roles in the pathogenesis of multiple myeloma (MM) remain uncertain. This study combined bioinformatic analysis and experimental validation to investigate the expression pattern of HKDC1 in MM. Transcriptomic data from public databases were analysed to explore the expression levels of HKDC1 in different stages of MM. Kaplan-Meier analysis was performed to evaluate the impact of HKDC1 expression on event-free survival (EFS) of MM patients. HKDC1 expression levels were then validated in clinical samples and cell lines using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Bioinformatic analysis of public databases revealed that HKDC1 was downregulated in monoclonal gammopathy of undetermined significance (MGUS), MM, and relapsed MM compared to the normal plasma cells. Furthermore, low HKDC1 level was found to be associated with shorter EFS in MM patients. Experimental validation via RT-qPCR confirmed that HKDC1 is significantly downregulated in MM patients. Collectively, HKDC1 may play a part in the development and progression of MM, providing new insights into the molecular processes that underlie this condition.
References
Bong IPN, Esa E. Molecular genetic aberrations in the pathogenesis of multiple myeloma. Asian Biomed (Res Rev News). 2023;17(4):152-62. doi: 10.2478/abm-2023-0056.
Solimando AG, Malerba E, Leone P, Prete M, Terragna C, Cavo M, et al. Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche. Front Oncol. 2022;12:973836. doi: 10.3389/fonc.2022.973836.
Liu P, Luo Y, Wu H, Han Y, Wang S, Liu R, et al. HKDC1 functions as a glucose sensor and promotes metabolic adaptation and cancer growth via interaction with PHB2. Cell Death Differ. 2024;31(12):1595-610. doi: 10.1038/s41418-024-01392-5.
Zhou D, Duan Z, Li Z, Ge F, Wei R, Kong L. The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment. Front Pharmacol. 2022;13:1091779. doi: 10.3389/fphar.2022.1091779.
Zhao P, Yuan F, Xu L, Jin Z, Liu Y, Su J, et al. HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex. Cancer Lett. 2023;569:216305. doi: 10.1016/j.canlet.2023.216305.
Wang MQ, Chen YR, Xu HW, Zhan JR, Suo DQ, Wang JJ, et al. HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer. Cancer Sci. 2023;114(4):1365-77. doi: 10.1111/cas.15692.
Wu J, Chen J, Xi Y, Wang F, Sha H, Luo L, et al. High glucose induces epithelial-mesenchymal transition and results in the migration and invasion of colorectal cancer cells. Exp Ther Med. 2018;16(1):222-30. doi: 10.3892/etm.2018.6189.
Guo J, Ye F, Xie W, Zhang X, Zeng R, Sheng W, et al. The HOXC-AS2/miR-876-5p/HKDC1 axis regulates endometrial cancer progression in a high glucose-related tumor microenvironment. Cancer Science. 2022;113(7):2297–310. doi: 10.1111/cas.15384.
Pang Q, Huang S, Cao J. HKDC1 enhances the proliferation, migration and glycolysis of pancreatic adenocarcinoma and is linked to immune infiltration. J Cancer. 2024;15:1983–93. doi: 10.7150/jca.92823.
Zhang Y, Wang M, Ye L, Shen S, Zhang Y, Qian X, et al. HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression. Nat Commun. 2024;15(1):1314. doi: 10.1038/s41467-024-45712-2.
Wang X, Shi B, Zhao Y, Lu Q, Fei X, Lu C, et al. HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK/mTOR signaling pathway. Cancer Cell Int. 2020;20:450. doi: 10.1186/s12935-020-01539-7.
Chen H, Li X, Yang L, Ye C, Chen Z, Wang Z. CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer. Environ Toxicol. 2024;39:1617–30. doi: 10.1002/tox.24061.
Zhang Z, Huang S, Wang H, Wu J, Chen D, Peng B, et al. High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma. Biochem Biophys Res Commun. 2016;474(4):673-9. doi: 10.1016/j.bbrc.2016.05.007.
Huang G, Zhang J, Gong L, Huang Y, Liu D. A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma. BMC Cancer. 2021;21:626. doi: 10.1186/s12885-021-08360-z.
Fuhr L, El-Athman R, Scrima R, Cela O, Carbone A, Knoop H, et al. The Circadian Clock Regulates Metabolic Phenotype Rewiring Via HKDC1 and Modulates Tumor Progression and Drug Response in Colorectal Cancer. EBioMedicine. 2018;33:105-21. doi: 10.1016/j.ebiom.2018.07.002.
Khan MW, Terry AR, Priyadarshini M, Ilievski V, Farooq Z, Guzman G, et al. The hexokinase "HKDC1" interaction with the mitochondria is essential for liver cancer progression. Cell Death Dis. 2022;13(7):660. doi: 10.1038/s41419-022-04999-z.
Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18-27. doi: 10.1016/j.neo.2022.01.001.
Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Rodriguez IP, Chakravarthi BVSK, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649-58. doi: 10.1016/j.neo.2017.05.002.
Dumas J, Gargano MA, Dancik GM. shinyGEO: a web-based application for analyzing Gene Expression Omnibus datasets. Bioinformatics. 2016;32(23):3679-81. doi: 10.1093/bioinformatics/btw519.
Posta M, Gyorffy B. Pathway-level mutational signatures predict breast cancer outcomes and reveal therapeutic targets. Br J Pharmaco. 2025;182(23):5734-47. doi.org/10.1111/bph.70215.
Luo X, Peng M, Wang Z, Wu N, Wang Y. HKDC1 in Cancer: Mechanisms, Clinical Applications, and Future. J Cancer. 2025;16(13):3851-8. doi:10.7150/jca.116277.
Liang Z, Zhang T, Huang J, Huang Z, Zhao Z, Cai S, et al. A comprehensive prognostic and immunological analysis of hexokinase domain containing protein-1 (HKDC1) in pan-cancer. Peer J. 2025;13:e19083. doi: 10.7717/peerj.19083.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Ivyna Pau Ni Bong, Nor Soleha Mohd Dali (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
