Nature Communications: New non-invasing tests can detect tumors four years earlier.

Late-stage tumors often lack effective treatment, and early diagnosis is reported to have a 5-year survival rate of 91% for early diagnosis, compared with 26% for patients with advanced initial diagnosis, so early diagnosis is critical for tumor treatment and improved patient prognosis.
there are screening methods in the clinic, including endoscopy, imaging and tumor markers, but these screenings still have some problems such as low diagnostic effectiveness and invasiveness, and the vast majority of tumors lack effective early screening methods.
circulating tumor DNA (circulating tumor DNA, ctDNA) and its methylation in plasma as a new type of non-invasive test, promising to be a promising method of tumor marker screening.
However, there are many problems with traditional methods of detecting ctDNA, such as very little ctDNA content in early patient plasma, tumor heteroglytic problems, and DNA loss caused by hydrosulphate conversion, so optimizing the detection of spot combination and improving sample conversion rate is the key to the application of ctDNA methylation testing to clinical practice.
, a recent study from Nature Communications described PanSeer, a blood-based cancer screening experiment.
large-scale retrospective longitudinal studies have shown that the method can achieve early diagnosis of multiple tumors up to four years in advance by detecting tumor-specific methylation markers.
The study first integrated genome-wide sulphate sequencing data (WGBS) in the TCGA database, tumor-related genomic regions reported in the literature, and genome-wide simplified methylation sequencing data (RRBS) from some tumor tissues, and developed a test combination of 595 genomic regions.
further obtained a set of 200 DNA samples isolated from fresh cancer and healthy tissues from BioChain, a commercial biological sample provider, which was processed using PanSeer analysis and identified 477 different methylation regions and 10,613 CpG bits.
Unlike the traditional method of combining sulphate sequencing and dual-chain library building, PanSeer uses a semi-targeted PCR method to build a single-chain library with high sensitivity, in addition, the method of deep sequencing of a large number of genomic regions can reduce the impact of patient variability or loss of targets.
the researchers selected some of the subjects in a retrospective study called TZL, which collected blood samples from subjects between 2007 and 2014 and preserved them for a long time.
Based on inclusion and exclusion criteria, a total of 223 subjects who were diagnosed with one of five common tumors (gastric, esothyroid, colorectal, lung or liver) were screened, 191 subjects who were initially healthy and were diagnosed with tumors within four years of collection and 414 subjects who were still healthy up to the end of follow-up.
were randomly divided into training queues and validation queues for the establishment and validation of disease diagnosis models.
based on the sample data of the training queue, the method detected 10613 CPG bits in 477 genomic regions selected and calculated the methylation fraction of each region in each sample, thus establishing a logistic regression classification model.
the classification model was used in the validation queue to first analyze healthy subjects and patients who had already been diagnosed with tumors at the time blood samples were taken, with 88% and 96% sensitivity and specificity, respectively.
, the classification model could detect tumors as early as four years in advance, with sensitivity of about 95%, among subjects who were healthy at the time of blood sample collection and later diagnosed with tumors.
the study, The PanSeer method was able to diagnose five common types of tumors within four years of a conventional diagnosis through big data-based DNA methylation analysis.
and the PanSeer method requires a small amount of blood samples, so it is envisaged that in the future the method could serve as a front-line screening for tumors, and that patients who are positive will be further examined to determine the presence of tumors.
Although it should be noted that PanSeer uses a generic set of methylation marker tests that contain genes that represent the core egedogenetic characteristics common to multiple cancers and therefore do not make specific diagnoses of tumor types.
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