Integrated Pan-Cancer Analysis and Functional Characterization of ATPSCKMT in Hepatocellular Carcinoma
5 affiliations
- 1Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Republic of Korea
- 2Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- 3Department of Anatomy, School of Medicine, Pusan National University, 49 Busandaehak-ro, Yangsan 50612, Republic of Korea
- 4Research Center for Molecular Control for Cancer Cell Diversity, Pusan National University, Yangsan 50612, Republic of Korea
- 5Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
Abstract
Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality, highlighting the need to identify functionally relevant molecular determinants. We systematically evaluated 38 genes classified as members of the methyltransferase-like (METTL) family and/or seven-β-strand lysine methyltransferases using pan-cancer genomic, transcriptomic, survival, and dependency datasets, followed by functional assessment in HCC cell lines. Integrated analysis prioritized ATP synthase c-subunit lysine methyltransferase (ATPSCKMT) for investigation in liver hepatocellular carcinoma (LIHC), where elevated expression was associated with adverse prognosis. DEMETER2 analysis also identified widespread RNAi dependency across cancer types. siRNA-mediated ATPSCKMT knockdown in JHH7 and HEP3B cells reduced CCK-8 signals and EdU incorporation. Network and co-expression analyses identified CCT5 as a representative ATPSCKMT-associated candidate, with reproducible positive correlations across independent HCC cohorts. In TCGA-LIHC, the ATPSCKMT–CCT5 correlation persisted after adjustment for shared local copy-number variation (partial Spearman ρ = 0.522). Single-cell analysis of primary HCC malignant hepatocytes further revealed patient-level co-detection, although these findings may be influenced by differences in transcript detection. Overall, our findings support further investigation of ATPSCKMT in HCC proliferation-associated phenotypes and identify CCT5 as a reproducible co-expression candidate.
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BibTeX
@article{kwon2026integrated,
title = {{Integrated Pan-Cancer Analysis and Functional Characterization of ATPSCKMT in Hepatocellular Carcinoma}},
author = {Soon Hyung Kwon and Ji Eon Ha and Sae-Ock Oh and Sang-Mo Kwon},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213887},
url = {https://www.mdpi.com/1420-3049/31/21/3887},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated Pan-Cancer Analysis and Functional Characterization of ATPSCKMT in Hepatocellular Carcinoma
AU - Soon Hyung Kwon
AU - Ji Eon Ha
AU - Sae-Ock Oh
AU - Sang-Mo Kwon
PY - 2026
DA - 2026/10/28
JO - Molecules
DO - 10.3390/molecules31213887
UR - https://www.mdpi.com/1420-3049/31/21/3887
AB - Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality, highlighting the need to identify functionally relevant molecular determinants. We systematically evaluated 38 genes classified as members of the methyltransferase-like (METTL) family and/or seven-β-strand lysine methyltransferases using pan-cancer genomic, transcriptomic, survival, and dependency datasets, followed by functional assessment in HCC cell lines. Integrated analysis prioritized ATP synthase c-subunit lysine methyltransferase (ATPSCKMT) for investigation in liver hepatocellular carcinoma (LIHC), where elevated expression was associated with adverse prognosis. DEMETER2 analysis also identified widespread RNAi dependency across cancer types. siRNA-mediated ATPSCKMT knockdown in JHH7 and HEP3B cells reduced CCK-8 signals and EdU incorporation. Network and co-expression analyses identified CCT5 as a representative ATPSCKMT-associated candidate, with reproducible positive correlations across independent HCC cohorts. In TCGA-LIHC, the ATPSCKMT–CCT5 correlation persisted after adjustment for shared local copy-number variation (partial Spearman ρ = 0.522). Single-cell analysis of primary HCC malignant hepatocytes further revealed patient-level co-detection, although these findings may be influenced by differences in transcript detection. Overall, our findings support further investigation of ATPSCKMT in HCC proliferation-associated phenotypes and identify CCT5 as a reproducible co-expression candidate.
SN - 1420-3049
ER -