The Changes of DNA Methylation in Tumor Development

China is a major cancer country, with over 4 million newly diagnosed patients and over 2 million deaths from cancer each year. The main reason is that early screening for cancer has not received sufficient attention. Many patients are found to be in the late or intermediate stages. What should these patients do? If patients want to survive, doctors also hope that patients can recover their health. However, at the current medical level, everyone feels helpless and helpless. But if we can detect cancer earlier and detect it before it occurs, it can effectively solve this problem, make a very important contribution to cancer patients, and significantly reduce the cost of cancer treatment. This is the goal of medical researchers.

Research has found that tumor DNA, especially circulating tumor DNA, can play a decisive role in early screening and diagnosis of tumors. Because in the early stages of cancer, when the tumor has only 100,000 to 10 million cells, it is not as big as a pea or fava bean. It has already released a lot of DNA into the blood, and testing can detect whether the patient has cancer.

In several very early articles around the world, it has been confirmed that there is a significant difference in the methylation sites between cancer and adjacent tissues. The methylation pattern in tumor cells is very different. Researchers conducted an experiment using over 3300 samples of tumor tissue, including over 700 samples from China. Proved: Firstly, DNA methylation can accurately distinguish various cancer tissues from normal tissues, with an accuracy rate of up to 98%. Secondly, DNA methylation can accurately locate the primary lesion of metastatic tumors. Thirdly, DNA methylation can effectively predict the prognosis of cancer patients, including survival curves.

This provides a solid foundation for using specific biomarker methylation to diagnose cancer. But that's not enough yet. Going for a biopsy and extracting tumor tissue for methylation detection can achieve an accuracy of over 90%, but this is very expensive and not easy. How can we do this in other ways? We thought of using liquid biopsy. Liquid biopsy is the process of using a tube of blood to detect circulating DNA in tumors. What is its principle? After the necrosis of tumor cells, fragments of the tumor will be released into the bloodstream, which can be detected in both the early and advanced stages of the tumor. Secondly, circulating tumor DNA, whose fragmented DNA is independent of cells, has many techniques available, such as circulating tumor cells. To perform this technique, it is necessary to keep live cells in the bloodstream, which is quite challenging.

The basic principle of ctDNA is that DNA methylation causes abnormal expression of tumor related genes, and some tumor cells' DNA enters the bloodstream to form ctDNA. ctDNA should circulate and flow in the human blood. Different parts of the tumor's ctDNA carry different methylation information. Through blood genetic testing, specific DNA methylation information can be detected, which can reveal the possibility of cancer transformation and achieve early diagnosis and treatment of cancer.

The researchers used 1000 liver cancer patients and 1000 ordinary patients for the study. Firstly, a comparison was made between the differences in tissue methylation sites and blood methylation, and these biomarkers were extracted using bioinformatics, machine learning, and artificial intelligence methods. The first time a methylation spectrum was measured in the blood, it was found that the aging biological clock played a very good role. They confirmed that the methylation changes in ctDNA in plasma were consistent with those in liver cancer tissue. They were able to identify key DNA methylation sites that distinguish liver cancer tissue from normal blood, and then screen out ten methylation sites in ctDNA, which can accurately diagnose the staging of liver cancer, including other prognostic work.

One of the important indicators is alpha fetoprotein. If you go for a physical examination, alpha fetoprotein is a necessary biomarker for liver cancer in a health check-up. However, as you can see, the red line represents the accuracy of AFT alpha fetoprotein. A CT score arrangement of 10 biomarkers can increase its accuracy by 50%, and the AUC can reach 96%, which plays a very accurate role in diagnosing liver cancer.

ctDNA methylation can accurately predict the responsiveness of patients to clinical treatment efficacy, including whether the tumor is completely removed during chemotherapy, radiotherapy, or surgery, whether there is recurrence after removal, and sensitivity to different drugs.

In addition, cancer is reproduced and biopsy is performed inside colon cancer. It also achieved a high accuracy rate here, including an AUC of 0.95%. In addition, there are still large-scale prospective clinical studies that demonstrate advantages over colonoscopy. Due to screening in our country, there may be 1 to 10 million people who need to undergo colonoscopy. Take out all gastroscopy and digestive doctors, and even if they perform colonoscopy day and night, they can only solve less than 1/10 of the problems. If a tube of blood is used to screen out patients with a high risk of cancer, and these patients are directly used for colonoscopy, their PPV or predictive ability will be much higher.