Application and development of noninvasive biomarkers for colorectal cancer screening: a systematic review

Abstract

Background: Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications. Main results: Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection. Conclusion: Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.

Disease Burden of Colorectal Cancer in China from 1990 to 2019: Age- and Sex-Specific Time Trends and 10-Year Forecast

“…The choice of CRC screening methods should be based on acceptability, diagnostic accuracy, cost-effectiveness, and the preferences of screening participants, aiming to enhance patient compliance with screening [44]. A comprehensive systematic review conducted by Song et al [42] evaluated the application and development of noninvasive biomarkers (including DNA mutations and methylation, mRNA and miRNA, gut microbiota, and metabolites, as well as low-throughput multi-omics combinations) in CRC screening. The expectation is that these promising biomarkers will more accurately identify early-stage CRC patients and be applied in the future.…”

“…In recent years, biomarkers have become crucial in cancer diagnosis, treatment, and prognosis, being applicable in various clinical settings such as risk assessment, early diagnosis, drug response evaluation, and prognosis prediction [40,41]. Currently, new noninvasive molecular detection methods, including tumor DNA, gut microbiota, and genomics screening, have become major drivers of the growing expenditure on CRC screening [42,43]. For instance, joint official guidelines from the Asian Pacific Association of Gastroenterology (APAGE) and the Asia-Pacific Society of Digestive Endoscopy (APSDE) emphasize the need to focus on general principles, advantages, limitations, clinical applications, and the future development of biomarkers (blood, feces) and noninvasive biomarkers (such as gut microbiota).…”

A commentary on ‘Application and development of noninvasive biomarkers for colorectal cancer screening: a systematic review’

“…When applied to a disease process, a biomarker can be used in diagnosis, prognosis, or to predict response to a pharmacological agent 3 . We read with great interest the article entitled ‘Application and development of noninvasive biomarkers for colorectal cancer screening: a systematic review’ 4 . In this study, Song et al .…”

“…In this study, Song et al . 4 discussed recent advances in novel diagnostic biomarkers for tumor tissue, blood, and stool samples in CRC patients.…”