Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas with <i>CDK4</i> -Amplification

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 <i>CDK4</i>-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 <i>CDK4</i>-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 <i>CDK4</i>-amplified CKS. A subset of the 14 genes demonstrated prognostic significance in <i>CDK4</i>-amplified patients from the TCGA cohort. Additionally, immune cell marker analysis showed associations between <i>CDK4</i>-amplification and innate immune cell signatures. Together, our findings identify promising therapeutic and prognostic targets linked to <i>CDK4</i>-amplification in CKS. These biomarkers warrant further investigation and may ultimately contribute to improved clinical outcomes for patients with CKS.