Discovery of Biomarkers Related to Colorectal Cancer by Systematic Proteomics Analysis and Experimental Procedures

Long non-coding RNAs (lncRNAs) play critical roles in gene expression regulation and have emerged as potential biomarkers for cancer diagnosis and treatment. This study aimed to investigate the potential role of two lncRNAs, LINC00943 and SLC9A3-AS1, as candidate biomarkers for colorectal cancer (CRC) diagnosis and therapy.

Initially, we investigated differentially expressed proteins (DEPs) in CRC through a comprehensive bioinformatics analysis and constructed a multi-layer regulatory network to understand the complex interactions. Subsequently, tissue samples were collected from CRC patients at Milad Hospital in Isfahan, Iran, between June and December 2021. The expression levels of LINC00943 and SLC9A3-AS1 were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Statistical analyses were performed using GraphPad Prism version 9. Expression differences between tumor and adjacent non-tumor tissues were evaluated using paired Student's t test. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate diagnostic performance. A P value less than 0.05 was considered statistically significant.

LINC00943 expression was significantly upregulated in tumor tissues compared to adjacent controls (P<0.0001), with strong diagnostic performance (AUC=0.8078, sensitivity=83.3%, specificity=76.7%). SLC9A3-AS1 also showed increased expression (P=0.0299), but with limited diagnostic value (AUC=0.6124). Network analysis identified SERBP1, KHSRP, and HNRNPA1 as central hub proteins, while miR-15b-5p and NEAT1 emerged as key regulatory elements.

These findings suggest that LINC00943 could serve as a valuable biomarker for CRC diagnosis and treatment, providing insights into the regulatory mechanisms underlying CRC pathogenesis. This manuscript has been released as a preprint at the Unraveling Candidate Biomarkers and Involved Biomedical Phenomena in Colorectal Cancer by Systematic Proteomics Analysis and Experimental Procedures. DOI: https://doi.org/10.21203/rs.3.rs-1974798/v1.