Evaluation of serum SNORA33 as a novel biomarker in colorectal cancer screening.

[BACKGROUND] Early screening for colorectal cancer (CRC) currently suffers from limited sensitivity(SEN), and the incidence and mortality rates remain high. There is a pressing need to develop more specific and sensitive diagnostic biomarkers. Small nucleolar RNAs (snoRNAs), a recently identified class of small non-coding RNAs(ncRNAs), are highly abundant and demonstrate exceptional stability in bodily fluids. These characteristics suggest their potential involvement in diverse biological regulatory processes. This study aims to identify and validate small nucleolar RNA (snoRNA) biomarkers that may aid in the diagnosis of colorectal cancer.

[METHODS] Through arraystar small RNA microarray analysis of six paired CRC and normal tissues, SNORA33 was identified as a candidate molecule. Its expression levels in tissues and serum were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and its stability was evaluated under various conditions, including gel electrophoresis, sequencing, dilution, incubation, and freeze-thaw cycles. Clinical relevance was assessed using chi-square tests, while diagnostic performance-both individually and in combination with carcinoembryonic antigen (CEA)-was evaluated via receiver operating characteristic (ROC) curve analysis. By analyzing the clinicopathological characteristics of CRC cases, the potential clinical utility of SNORA33 was assessed. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted based on genes associated with SNORA33 from the Cancer Genome Atlas (TCGA) database, providing insights into the biological functions and underlying molecular mechanisms of this non-coding RNA (ncRNA).

[RESULTS] In CRC, SNORA33 showed significant upregulation in tissues and serum, with a pronounced reduction observed after curative surgery; its elevated expression was closely linked to vascular invasion. The ROC curve demonstrated that serum SNORA33 alone already exhibits specific diagnostic performance and is independent of age. Its diagnostic efficacy is further enhanced when combined with conventional colorectal cancer markers, significantly improving the ability to distinguish between colorectal cancer, colitis, and healthy controls.

[CONCLUSION] SNORA33 holds promise as a diagnostic tool for CRC that is minimally influenced by age, with potential for clinical translation into a non-invasive biomarker for early diagnosis and surveillance.