The role of SARS1 in the progression of colorectal cancer: insights from clinical data and organoid models

Colorectal cancer (CRC) is a significant global health concern, with adenomas representing critical precancerous lesions. Early detection of adenomas is essential for reducing the incidence of CRC; however, effective biomarkers for the adenoma–carcinoma transition are currently lacking. Serine tRNA ligase (SARS1) has been identified in colorectal adenoma tissues, but its biological role remains unclear. Here, we analyzed SARS1 expression in colorectal adenoma and colorectal cancer using data from the GEO and TCGA databases, as well as immunohistochemical staining of 48 tissue pairs (normal colorectal mucosa, adenoma lesion, and cancer lesion). SARS1 expression was significantly higher in adenomas and cancers compared to normal colorectal mucosa, decreasing from the adenoma to cancer stages. High SARS1 expression was associated with improved overall survival (OS; Log-rank P = 0.0209) and progression-free survival (PFS; Log-rank P = 0.0147) in patients with CRC. As demonstrated by immunofluorescence and qRT-PCR, in colorectal adenoma organoids, SARS1 knockdown was associated with decreased expression of LGR5 and OLFM4, and increased expression of c-Myc. This gene expression profile mirrors that observed in colorectal cancer organoids, as reported in previous studies. Additionally, the downregulation of SARS1 also enhanced the proliferation of CRC cells and the viability of colorectal adenoma organoids ( p < 0.01 to p < 0.0001). Our findings suggest that SARS1 exerts context-dependent, stage-associated growth-suppressive effects during the adenoma-to-carcinoma transition, and its downregulation is associated with colorectal cancer progression. SARS1 represents a candidate marker reflecting adenoma-to-carcinoma progression; however, its clinical utility as a diagnostic or prognostic tool requires independent validation in larger, independent, adequately powered cohorts, and its precise functional mechanisms warrant further investigation.