Regulatory RNA Properties and Diagnostic Performance of the Non-Coding Transcript ENST00000453316 Across Solid Tumors

Background: Recent pan-cancer transcriptome analyses have identified ENST00000453316 as a cancer biomarker candidate, showing consistent and significant deregulation across multiple cancer types. Methods: This study investigated the transcript as a regulatory RNA in cancer-associated processes and its potential as a biomarker using a bioinformatics approach. Results: In silico characterization classified ENST00000453316 as a non-coding transcript with regulatory features and stable structure. Curated annotations documented the binding of 21 RNA-binding proteins across the transcript region, with core spliceosomal factors at the unique splice junction and cytoplasmic 3′-end factors at the terminal exon, in agreement with the sequence-based predictions. Promoter analysis revealed a TATA-less, CpG-poor region with multiple putative transcriptional regulator binding sites. Its expression was higher in most solid tumor types analyzed, with minimal expression in non-tumor tissues, indicating a tumor-associated pattern. Discrimination between tumor and adjacent non-tumor tissue within TCGA was good in five of the ten tissue types with sufficient adjacent-normal samples, with the area under the ROC curve reaching 0.82 in the lung, 0.78 in the bladder and 0.71–0.75 in the colon, breast and stomach, but close to chance in the kidney, thyroid and prostate. Conclusions: These results suggest that ENST00000453316 is a cancer-associated, promoter-driven non-coding transcript with potential regulatory relevance. Despite its revised annotation, it exemplifies how alternative promoter usage generates biologically and clinically meaningful transcripts contributing to tumor-specific gene regulation. Future experimental validation is needed to confirm the role of ENST00000453316 as a functional regulatory RNA and assess its clinical potential as a cancer biomarker.