The study discusses the challenges associated with the HNSCC metastasis and aims to identify hub genes related to the Cancer Stem Cells and metastasis in HNSCC through bioinformatics analysis. HNSCC is a prevalent type of cancer having a low five-year rate of survival, largely due to advanced stages at diagnosis and distant metastasis. The study hypothesizes that CTCs with CSC characteristics are responsible for metastasis. To investigate, we utilized mRNA-based stemness index (mRNAsi) and WGCNA on transcriptomic data by TCGA HNSCC cohort. The study involved multiple analytical steps, including DGE analysis, co-expression network, functional enrichment, hub gene identification, PPI network, and survival evaluation. The results revealed 18 hub genes associated with CSCs and metastasis in HNSCC. Further screening narrowed the hub gene list to nine genes, CDC45, MCM5, ASF1B, RFC4, E2F1, TK1, CHTF18, CENPM, and CDCA3.These genes have been discovered to be up-regulated in the samples of HNSCC compared to normal tissues. Highlighted for potential prognostic significance in HNSCC patients, CHTF18 and CDC45, with CDC45 playing a role in DNA replication, are associated with metastasis and CSC-like behavior. The study offers insights into potential hub genes associated with CSCs and metastasis in HNSCC. However, further experimental validation and clinical data integration are necessary to confirm these findings and establish clinical relevance. This study utilizes bioinformatics tools to identify genes influencing metastatic behavior in HNSCC, revealing potential therapeutic targets and underscoring the intricacies of cancer metastasis. Other hub genes are linked to various cancers, promoting invasion, proliferation, and migration.
