Abstract
Colorectal cancer often presents as a highly variable disease with myriad forms that are at times difficult to detect in early screenings with sufficient accuracy, for which novel diagnostic methods are an attractive and valuable area of improvement. To improve colorectal cancer diagnosis and prognosis, new biomarkers that can be assembled into a diagnostic panel must be identified, and tRNA-derived small RNAs (tsRNAs) are a particularly interesting and increasingly visible new class of molecules to examine. In this study, small RNA-seq data were profiled for the expression of 104 human tsRNAs in tumor tissue and adjacent normal tissue samples, and a diagnostic model was built based on four differentially expressed tsRNAs: tRF-22-WB86Q3P92, tRF-22-WE8SPOX52, tRF-22-WE8S68L52, tRF-18-8R1546D2. Furthermore, the diagnostic model was validated by two independent validation datasets (AUC was 0.97 and 0.99), and a LASSO model was applied to develop a seven-tsRNA-based risk score model for colorectal cancer prognosis. Finally, a tsRNA-mRNA interaction network was established according to potential mRNA targets predicted by bioinformatic methods. In conclusion, the results suggest that abnormal expression of tsRNA in colorectal cancer may have a functional effect on tumor action and moreover, that some of the tsRNAs identified in this study with diagnostic and prognostic potential could be of clinical significance.
Highlights
Colorectal cancer (CRC) is currently one of the most common types of cancers in the world, with incidence and mortality rates increasing over the last 25 years in adults under the age of 50 [1,2,3]
Patients who participated in flexible sigmoidoscopy for screening of CRC have shown significantly reduced incidence and mortality rates that were sustained over the long term, but the US Preventative Services Task Force still reports a lack of definitive evidence for a single-best screening approach, and current methods for early detection such as the endoscopy are typically fairly invasive [9, 10]
This study explores the potential of tRNA-derived small RNA to address this immense need
Summary
Colorectal cancer (CRC) is currently one of the most common types of cancers in the world, with incidence and mortality rates increasing over the last 25 years in adults under the age of 50 [1,2,3]. CRC is not isolated to developing countries, but on the contrary is an issue much more pronounced in high HDI countries: for example, according to the CDC, in the United States alone, 141,270 new CRC cases emerged in 2016 with 52,286 deaths [5] Despite these harrowing statistics, colorectal cancer is one of the most preventable types of cancer with a high survival rate after early detection. In liver cancer, regulation of tsRNA expression was found to be associated with overall survival of the disease [21] Taken together, these important results indicate the potential clinical and biological importance of tsRNA, yet they highlight the vast space for future research to improve our understanding of these ncRNAs. There are many questions about the biogenesis of tsRNA and their precise roles and mechanisms within the body that remain to be illuminated, and whether the expression profile of tsRNAs could present a stable bloodborne signal representative of the internal tumor state for use in a clinical setting. Research in tsRNAs promises exciting new applications and discoveries, and efforts to elucidate their poorly understood background and clinical significance represent an important and emerging facet of cancer research at large. tsRNAs are a prime candidate for further examination towards achieving the goal of addressing the immense needs for accessible, noninvasive, accurate early CRC screening methods described, and even as a potential therapeutic target
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