Decoding Osteosarcoma's Lactylation Gene Expression: Insights Into Prognosis, Immune Dynamics, and Treatment.

Abstract

Osteosarcoma (OS), characterized by a complex tumor microenvironment, poses challenges in treatment, metastasis, and therapy resistance. This study examined the impact of lactylation, a posttranslational modification, on gene expression and tumor behavior in OS, particularly its influence on prognosis, immune cell infiltration, and chemotherapy response. Utilizing data from the Gene Expression Omnibus series accession number 21257 (GSE21257) and the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) datasets, the investigation focused on analyzing the expression profiles of 267 lactylation modifier genes, which were selected from a total of 336 lactylation-related genes compiled from various studies in the literature. The methods included unsupervised clustering using "ConsensusClusterPlus" heatmap generation with "pheatmap" pathway analysis from several databases, and immune cell infiltration assessment using the "single-sample Gene Set Enrichment Analysis (ssGSEA)" function. The research revealed 36 significant lactylation-related genes in OS, categorizing them into two clusters with distinct survival and biological characteristics. One cluster demonstrated poor prognosis due to increased tumor cell proliferation and specific immune cell variations, also showcasing genes that enhance tumor growth and metastasis, thus indicating its aggressive nature and adverse outcomes for patients. These insights are crucial for understanding the molecular mechanisms of OS and identifying therapeutic targets. Therefore, the study elucidates the role of lactylation-related genes in the prognosis, pathogenesis, and treatment response of OS, laying the groundwork for further exploration into potential therapeutic targets and the underlying mechanisms within OS.