Defining distinct LncRNA signatures for precancerous lesions and tumors in colorectal cancer screening

Abstract

Colorectal cancer (CRC) screening via video-colonoscopy is recommended for individuals aged 45 and above to meticulously examine the colon and rectum, aiding early polyp detection and prevention of CRC. Colonoscopy’s preventive integration has significantly led to identifying precancerous adenomas and latent cancers, emphasizing the challenge of comprehending adenoma and tumor molecular diversity, driving precision medicine approaches. LncRNAs dysregulation contributes to colorectal tumorigenesis and affects clinical manifestations, such as tumor size, stage, patient survival, and treatment outcomes. These findings position LncRNAs as biomarkers and therapeutic targets in cancer. Currently, distinctive LncRNA signatures for precancerous CRC lesions or molecular subtypes (CMS) defining tumors are lacking. To address this, through comprehensive bioinformatics analysis from RNA-seq and microarrays data, we defined distinct LncRNA signatures for CMS1- 4 subtypes in tumors and colorectal adenomas with classificatory (AUC>0.8), prognostic (p<0.05) and predictive value (p adj.<0.01, treatment response). These signatures are being validated by qRTPCR in preoperative biopsy and plasma samples from individuals with adenomas or CRC, and in cell line models with proliferation and chemoresistance variations. We have refined protocols for patient inclusion, sample collection, RNA extraction, and LncRNA detection.