Novel biomarkers for neoplastic progression from ulcerative colitis to colorectal cancer: a systems biology approach

Abstract

In recent studies, the void of evaluation and in-depth understanding of unknown clinically relevant potential molecular biomarkers involved in colorectal cancer (CRC) from the inflammatory stage of ulcerative colitis (UC) to CRC metastasis, which can be suitable therapeutic targets, is deeply felt. The regulation and interaction among different cancer-promoting molecules, including messenger RNAs (mRNAs) and micro RNAs (miRNAs) in CRC and its progression, were the aim we pursued in this study. Using microarray data, we investigated the differential expression for five datasets, including mRNA and microRNA samples related to UC, tumor/normal. Then, using robust data analysis, separate lists of differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were identified, which were used for robust rank aggregation (RRA) and co-expression network analysis. Then, comprehensive computational systems biology analyses, including gene ontology and Kyoto encyclopedia of genes and genomic pathway enrichment analyses, mRNA-miRNA regulatory network, and survival analysis, were employed to achieve the aim of this study. Finally, we used clinical samples to validate this potential and new target. According to this systems biology approach, a total of 98 DEGs and 8 DEmiRNAs with common differential expression were identified. By combining the distinct results of RRA and network, several potential therapeutic targets, and predictive and prognostic biomarkers for UC and CRC were identified. These targets include six common hub genes, CXCL1, CXCL8, MMP7, SLCA16A9, PLAU, and TIMP1, which are upregulated. Among these, the important and new biomarker SLC16A9 is negatively regulated by hsa-mir-194-5p, and hsa-miR-378a-5p take. The findings of the present study provide new insight into the pathogenesis of CRC in UC. Our study suggests future evaluation of the functional role of SLC16A9 and hsa-mir-194-5p and hsa-miR-378a-5p in CRC development.

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

“…8 Kaplan-Meier plots demonstrating the relationship between HAND2-AS1 expression and overall survival (OS) in diverse cancers, highlighting significant outcomes. The pink line signifies high expression groups, while the black line corresponds to the low expression group prognosis of this disease [25][26][27]. In this study, the analyses identified 2299 genes, and by identifying the important interactions of lncRNA-mRNA, the Co-expression and regulatory network of mRNA-lncRNA in CRC has been investigated.…”

“…This phenomenon is especially pronounced in CRC and other malignancies [27]. Based on our team's previous studies aimed at identifying important biomarkers in CRC, we performed a comprehensive transcriptome analysis of lncRNA-mRNA interactions to identify further biomarkers that could aid in the diagnosis, treatment, and prognosis of this disease [28][29][30]. In this study, the analyses identi ed 2299 genes, and by identifying the important interactions of lncRNA-mRNA, the Co-expression and regulatory network of mRNA-lncRNA in CRC has been investigated.…”

A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer

“…The aim of our study was to identify, by miRNA profiling and subsequent bioinformatic validation, potential biomarkers of UC disease progression to colorectal cancer. Some microarray-based studies have identified gene expression profiles in UC and CRC [ 15 ]. Long-term inflammatory bowel disease increases the risk of CRC; thus, we enrolled patients with a UC disease for at least 10 years [ 16 ].…”

Krüppel-like Factor 4, A Potential Therapeutic Agent for Colorectal Cancer: A Bioinformatics Analysis

“…1,2 However, these approaches are most effective when applied during the early stages of the disease. 3 While the 5-year survival rate for CRC patients is approximately 90% in the early stages, it drops below 5% in cases with distant metastases. 4 Limitations in the existing treatment strategies and CRC's high metastatic potential contribute to the detection of the disease at advanced stages, leading to an increase in mortality rates.…”