Sno-derived RNAs are prevalent molecular markers of cancer immunity

Small nucleolar RNAs (snoRNAs) constitute a family of noncoding RNAs that are classically known as guide RNAs for processing and modification of ribosomal RNAs. Recently, it was discovered that snoRNAs can be further processed into sno-derived RNAs (sdRNAs), some of which are known to exhibit microRNA-like properties. SdRNAs have been implicated in human cancer; however, a systems-level sdRNA landscape in human cancers is lacking. Through integrative analysis of ~22 nt size-selected smRNA-seq datasets from 10,262 patient samples across 32 cancer types, we mapped a pan-cancer sdRNAome and interrogated its signatures in multiple clinically relevant features, particularly cancer immunity and clinical outcome. Aggregating sdRNA abundances by parental snoRNAs, these expression signatures alone are sufficient to distinguish patients with distinct cancer types. Interestingly, a large panel of sdRNAs are significantly correlated with features of the tumor-immune microenvironment, such as immunosuppressive markers, CD8⁺ T cell infiltration, cytolytic T cell activity, and tumor vasculature. A set of individual sdRNAs with tumor-immune signatures can also stratify patient survival. These findings implicate snoRNAs and their derivative sdRNAs as a class of prevalent noncoding molecular markers of human cancer immunity.