CEMIP1 and TACSTD2 as circulating mRNA biomarkers for early detection and tumor burden assessment in colorectal neoplasia

BACKGROUND: Early and minimally invasive detection of colorectal neoplasia remains a major challenge in cancer prevention. Current blood-based screening approaches lack sufficient sensitivity for early-stage lesions and advanced adenomas, highlighting the need for novel circulating biomarkers. METHODS: This study employs an integrative multi-phase approach combining whole-transcriptome RNA sequencing (RNA-seq) [patients with colorectal adenoma (CRA), n = 16; patients with colorectal cancer (CRC), n = 7; healthy controls, n = 10] with two-step RT-qPCR validation in tissue and plasma samples (CRA, n = 48; CRC, n = 48 for each TNM stage I-III and n = 42 for TNM IV; healthy controls n = 51). The study design encompasses discovery, validation, and liquid biopsy phases, enabling systematic prioritization of candidate genes across independent cohorts. This strategy was used to identify circulating mRNA biomarkers for early detection and monitoring of CRA (including both advanced and non-advanced adenomas) and CRC across the adenoma-carcinoma sequence, including pre- and post-operative plasma collections. RESULTS: RNA-seq analyses identified over 4,000 differentially expressed genes in CRA and CRC tissues compared to matched adjacent mucosa and colonic mucosa from healthy controls. Subsequent validation confirmed a consistent upregulation of several candidates, with TACSTD2 and CEMIP1 emerging as the most robust and biologically relevant. Both genes showed concordant expression patterns between tissue and plasma, supporting their detectability in liquid biopsy. TACSTD2 was markedly upregulated in CRA tissue and plasma, indicating its utility as an early biomarker of neoplastic transformation. Importantly, its elevation in premalignant lesions suggests a potential future contribution to biomarker-based risk stratification and screening settings. CEMIP1 mRNA levels were significantly elevated in CRC tissue and plasma and declined following tumor resection, reflecting a strong association with tumor burden. CONCLUSIONS: By integrating tissue and liquid biopsy analyses, this study identifies TACSTD2 and CEMIP1 as promising circulating mRNA biomarkers for early detection and post-surgical monitoring of colorectal neoplasia. Their complementary biological roles across different stages of tumorigenesis support their combined use in a multiplex diagnostic approach. These findings support the clinical translation of mRNA-based biomarkers into non-invasive diagnostic tools with the potential to enhance CRC screening and personalized patient management.