Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas with CDK4-Amplification

  • Eun-Young Lee (Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Hyun Sang Cho (Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • June Hyuk Kim (Department of Cancer Biomedical Science, NCC-GCSP, National Cancer Center) ;
  • Hyun Guy Kang (Department of Cancer Biomedical Science, NCC-GCSP, National Cancer Center) ;
  • Jong Woong Park (Department of Orthopaedic Surgery, National Cancer Center Hospital, National Cancer Center) ;
  • Ahyoung Cho (Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Hye Jin You (Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center)
  • Received : 2025.08.18
  • Accepted : 2026.01.16
  • Published : 2026.03.01
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Abstract

Soft tissue sarcomas (STSs), a diverse group of mesenchymal malignancies, are characterized primarily by copy-number alterations rather than a high tumor mutation burden. In this study, we sought to identify expression-based biomarkers in complex karyotype STS (CKS) with CDK4-amplification to support improved therapeutic strategies. Using transcriptome data from National Cancer Center (NCC)-CKS samples, we selected genes whose expression levels were more than two-fold higher or less than half in tumor tissues compared with normal tissues. These genes were further filtered by CDK4-amplification status, resulting in 30 candidates, which were refined to 14 differentially expressed genes (DEGs) based on false discovery rate (FDR) significance. Bioinformatics analyses revealed enriched pathways and gene-gene networks related to redox regulation and growth-factor-driven signal transduction, indicating metabolic alterations that may promote tumor survival in CDK4-amplified CKS. A subset of the 14 genes demonstrated prognostic significance in CDK4-amplified patients from the TCGA cohort. Additionally, immune cell marker analysis showed associations between CDK4-amplification and innate immune cell signatures. Together, our findings identify promising therapeutic and prognostic targets linked to CDK4-amplification in CKS. These biomarkers warrant further investigation and may ultimately contribute to improved clinical outcomes for patients with CKS.

Keywords

Acknowledgement

We thank Young Ho Kim (National Cancer Center), Ms. Jung Yeon Yu (National Cancer Center) for their technical support and Mi Ae Kim of the Imaging core (National Cancer Center) for her expert assistance and helpful suggestions. This work was supported in part by NCC-2311420 (to H.Y.), NCC-2410760 (to H.Y.) and NCC-2410861 (to H.Y.).

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