This study conducted a comprehensive analysis of the functions of the c-ROS oncogene 1 receptor tyrosine kinase (ROS1) gene in its non-fusion state across various cancer types, utilizing databases and datasets such as University of California, Santa Cruz (UCSC) Genome Browser and The Cancer Genome Atlas (TCGA). Expression profiling across 33 cancer types demonstrated significant tissue heterogeneity: ROS1 was significantly upregulated in 13 cancer types, including UCEC and CESC (p<1e-13), and downregulated in 14 cancer types, such as GBM and KIRC (p<0.05). Survival analysis revealed that elevated ROS1 expression was an independent prognostic indicator of poor outcomes in seven cancers, including glioblastoma (HR=4.26, p=4.4e-5). Furthermore, immune infiltration analysis identified significant associations with the tumor microenvironment in eight cancer types, with a positive correlation observed in seven types, such as LUAD, and a negative correlation in LGG. Correlation analyses between genomic heterogeneity and gene expression further substantiated that ROS1 expression exhibited a negative correlation with tumor mutational burden (TMB) in lung adenocarcinoma (LUAD) (R=0.25, p<1e-8), a strong negative correlation with tumor purity in lung squamous cell carcinoma (LUSC) (R=-0.34, p<1e-13), and a positive correlation with homologous recombination deficiency (HRD) in kidney cancer (R>0.50, p<1e-10). These findings imply that ROS1 plays a role in non-fusion carcinogenesis by modulating immune responses and genomic stability, thereby providing novel evidence for the development of targeted therapies and immune combination strategies.
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Wang, Z., Yuan, Y., Wang, Y., Hou, Z., Dou, X., Wang, J., Xu, M., Wang, C., Guo, G., Liao, W. (2025) Characteristics of ROS1 Non-fusion Expression in Pan-cancer: Expression Heterogeneity, Prognostic Value and Association with Immune Microenvironment and Genomic Stability. Scientific Research Bulletin, 2(4), 68-79.
https://doi.org/10.71052/srb2024/PMBG9311