Reporter : Xing Yu
Publisher : China Science News
Direct translation
Image : Web Screenshot (WebMD).
In recent years, circulating tumor DNA (ctDNA) in the blood has become a promising cancer biomarker, that is, "liquid biopsy". ctDNA has been proven to be of great value in non-invasive detection of cancer, individualized treatment of advanced cancer, and monitoring during and after treatment.
A few days ago, the Taizhou Institute of Health Sciences of Fudan University and the Institute of Human Phenotype Group, in conjunction with the University of California, San Diego, and Qilu Hospital of Shandong University, published results in Nature-Communications, stating that the team developed a non-invasive blood test— -CtDNA methylation multi-cancer screening technology PanSeer, may be able to make early detection of 5 common cancers 4 years before routine diagnosis.
Targeting ctDNA methylation
At present, the incidence and mortality of malignant tumors are increasing year by year, and early detection of tumors is essential for cancer treatment. Currently, the only cancer screenings are for several specific cancer types, such as colonoscopy, prostate specific antigen, etc.
To verify and research early tumor detection and screening, not only high-efficiency and sensitive technology is needed, but more importantly, blood and biological samples must be sampled before the diagnosis of tumor patients. Chen Xingdong, the first author of the paper and a researcher at the Taizhou Institute of Health Sciences of Fudan University and the Institute of Human Phenotype Group, said that this means that large, long-term population cohort data is needed to support the exploration of new early cancer screening technologies.
Based on the Taizhou cohort built by Fudan University, the research team began to screen research subjects. So far, nearly 200,000 community people have participated in the study. Through systematic cohort follow-up, the research team tracked the occurrence of various major chronic diseases in the cohort for a long time, and tracked and collected more than 1.5 million various biological samples from asymptomatic people at multiple time points for long-term preservation.
Chen Xingdong said that early in the development of the disease, even several years before asymptomatic and undiagnosed, there are cancer signals in the blood of cancer patients. The research results published this time included 191 blood samples from patients who were diagnosed with tumors 1 to 4 years after the sampling time point, 223 blood samples from tumor patients collected at the local hospital after the diagnosis, and 414 patients who had not been followed up for more than 10 years. Samples of patients diagnosed with tumors were used as control populations. Among them, the cancers of the confirmed tumor patients are colon cancer, esophageal cancer, liver cancer, lung cancer and stomach cancer. Based on the above data, the researchers discovered the specificity of ctDNA methylation in the blood of the above five cancer patients.
ctDNA is the somatic DNA of tumor cells released into the circulatory system after shedding or apoptosis, and is a characteristic tumor biomarker. Through ctDNA detection, tumor traces in the blood can be detected.
"CtDNA methylation is a signal of tumorigenesis. Before reaching the current clinical diagnosis gold standard, ctDNA methylation exists in the blood circulation even before the patient has symptoms. The DNA of tumor cells and normal cells Methylation is different. Therefore, by capturing ctDNA in the blood and detecting its methylation characteristics, the occurrence of tumors can be judged in advance." Chen Xingdong told China Science Daily.
High sensitivity and specificity of screening technology
Based on the characteristics of ctDNA methylation, researchers have developed and designed PanSeer technology. PanSeer is a semi-targeted technology that can accurately screen out very tiny ctDNA methylation levels in the human body.
"Because the content of ctDNA in the blood is very small, the first problem we need to solve is to enrich the ctDNA in the blood." Chen Xingdong pointed out that another key point of the detection method is the need to identify specific genes for cancer methylation screening .
In order to strictly control the common hidden dangers of overfitting in big data analysis, the research team used a combination of calculating the average methylation level of each target genome region in the sample and the ensemble logistic regression classifier, and fully considered a large number of interference factors to complete Build a classification model to distinguish between healthy patients and cancer patients.
To further understand the precision and accuracy of the method, the study additionally analyzed the plasma samples of 223 cancer patients and 200 primary tumors and normal tissues. In an independent test sample set, the research team reproduced 96% specificity of 207 healthy control samples, and PanSeer technology reached 88% sensitivity on 113 patient samples collected after diagnosis. Next, in 98 samples collected 1-4 years before the diagnosis, PanSeer technology reached 95% detection sensitivity.
The study found that the detection sensitivity of this original technology for five different cancer types, including colorectal cancer, esophageal cancer, liver cancer, lung cancer and gastric cancer, was similar in blood samples collected at different times before diagnosis. This shows that cancer signals will exist in the blood early in the development of the disease, even several years before asymptomatic and undiagnosed.
"In other words, the study has been able to prove in a strict sense that PanSeer technology can detect cancer earlier than traditional diagnostic methods." Chen Xingdong said.
Early cancer screening can be expected in the future
Currently, blood tests used for cancer diagnosis include complete blood count, blood protein test, tumor marker test and ctDNA test. Chen Xingdong introduced that blood testing methods commonly used clinically are mostly assisted in tumor diagnosis. "Tumor blood tests are generally used in conjunction with imaging tests, and blood tests are not particularly effective in diagnosing tumors, and early diagnosis cannot be achieved."
Large population cohort research is one of the main supporting platforms for biomedical research. Jin Li, the corresponding author of the study, academician of the Chinese Academy of Sciences, and dean of the Taizhou Institute of Health Sciences and the Institute of Human Phenotype Group of Fudan University, pointed out that combining the Taizhou cohort study and PanSeer technology can at least prove that early cancer screening can be done through non-invasive blood testing, which is convenient "Early detection" followed by "early intervention" for asymptomatic cancer-susceptible people has very important application value.
The characteristics of the five tumors involved in the study have certain similarities, and they have a heavy burden on my country. Next, the research team will expand the screening range of cancer types to include liver cancer, cervical cancer, pre-adenocarcinoma, breast cancer and other tumors.
"At present, PanSeer technology cannot determine which tumors the positive patients have. In the next step, we will further optimize the sequencing method and clarify the tumor type." Chen Xingdong said that the team will carry out cohort studies in multiple centers across the country to expand the verification and promotion of regional populations jobs.
Samantha Harrison, a senior expert at Cancer Research UK, said: "PanSeer detection technology has achieved encouraging preliminary results. What's more gratifying is that it can detect cancer in blood samples at least 4 years in advance. Even if these are only early results, but It only needs to be verified by a larger study, and I look forward to that day very much."
Related paper information: https://doi.org/10.1038/s41467-020-17316-z
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