Colorectal cancer is the third most fatal cancer of the digestive tract. The incidence of new cases in our country is about 400,000 per year, and the incidence is increasing year by year. The early symptoms of colorectal cancer are not obvious, it is easy to attribute to living habits and neglect, most patients have been diagnosed in the middle and late stages, and the survival rate after surgery and chemotherapy is still low. therefore, efficient universal diagnosis of colorectal cancer is crucial for the prognosis and treatment of the disease.
at present, enteroscopy is the most intuitive and effective method for clinical examination of colorectal lesions, but this invasive detection has time-consuming, expensive, low patient compliance and other defects. Liquid biopsy is a new method of tumor detection, which is based on the analysis of non-solid biological tissue such as blood for in vitro diagnosis. Colorectal cancer biomarkers of serum carcinoembryonic antigen (CEA) have been used in clinic, but only 40% to 60% of patients can be detected with low sensitivity. Professor Xu Ruihua of Sun Yat-sen University, published in the journal ScienceTransational Medicine on January 1, found specific ctDNA methylation sites that can be used for liquid biopsy, and opened up non-invasive new methods for efficient and convenient diagnosis and prognosis of colorectal cancer!
Professor Xu Ruihua is the co-author of the article, including deputy chief physician of the Cancer Prevention and Treatment Center of Zhongshan University, associate researcher Zhao Qi and chief physician Wei Wei. )
circulating tumor dna (ctdna) is free dna (cfdna) released into the blood after necrosis or apoptosis of tumor cells. as part of tumor cell fragments, cfdna has been deeply branded as a specific source, reflected in the specifically expressed mutant genes in tumors as well as epigenetic abnormalities. the analysis and detection of cfdna has been developed as an important branch in liquid biopsy with inestimable application prospects.
DNA methylation is the most common epigenetic modification, which is related to a series of physiological and pathological processes such as differentiation and development, aging, and the methylation of tumor suppressor gene is one of the early markers of tumorigenesis. although sites such as sept9 have been identified as iconic sites for cfdna methylation in colorectal cancer, the accuracy of single-site methylation detection has been challenged due to patient individual differences and low body fluid cfdna content. considering that methyltransferase or demethylase may simultaneously modify adjacent cpg sites in the same dna strand, cfdna methylation profiling of “methylation-related blocks ” will greatly improve diagnostic and other accuracy.
first, researchers collected genome-wide screening of tissue samples from colorectal cancer patients and methylation data of their cfdna. bioinformatics analysis identified nine cfdna methylation markers associated with colorectal cancer occurrence, based on diagnostic scores established by the algorithm (cd-score) to predict colorectal cancer. colorectal cancer and healthy subjects were divided into modeling group and validation group at a ratio of 2:1. the diagnostic accuracy of colorectal cancer was up to 96%, and the diagnostic sensitivity of validation group was up to% and specificity was up to%, which far exceeded the diagnostic efficacy of serum cancer embryo antigen CEA markers for clinical application.
Furthermore, researchers tracked more than 900 subjects over an average period of time, combining colonoscopy and cfdna methylation data to identify five prognostic markers for colorectal cancer; that is, the cp-score score for these iconic methylation sites could almost accurately predict patient survival, far outperforming commonly used prognostic markers such as primary tumor site, tmn stage, and cea.
In addition, in cfdna data from colorectal cancer patients, the researchers found that colorectal cancer was classified into two categories based on 45 marker sites with significant methylation differences. Type 1 was more common in women with left colon lesions and type 2 had a lower survival rate. this differentiates colorectal cancer subtypes from the molecular level, suggesting the correlation of intrinsic biological mechanisms with clinicopathological progression.
this study demonstrates the accuracy and sensitivity of a range of methylation markers of cfdna for colorectal cancer diagnosis, prognosis, and disease detection through methylation profiling, providing non-invasive molecular means for early detection of mildly symptomatic colorectal cancer with great clinical promise!