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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.

ABSTRACT: Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.

SUBMITTER: Chen X

PROVIDER: S-EPMC7374162 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.

Chen Xingdong X Gole Jeffrey J Gore Athurva A He Qiye Q Lu Ming M Min Jun J Yuan Ziyu Z Yang Xiaorong X Jiang Yanfeng Y Zhang Tiejun T Suo Chen C Li Xiaojie X Cheng Lei L Zhang Zhenhua Z Niu Hongyu H Li Zhe Z Xie Zhen Z Shi Han H Zhang Xiang X Fan Min M Wang Xiaofeng X Yang Yajun Y Dang Justin J McConnell Catie C Zhang Juan J Wang Jiucun J Yu Shunzhang S Ye Weimin W Gao Yuan Y Zhang Kun K Liu Rui R Jin Li L

Nature communications 20200721 1

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma sampl ...[more]

PMID: 32694610

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Project description:Background:One of the most significant challenges in colorectal cancer (CRC) management is the use of compliant early stage population-based diagnostic tests as adjuncts to confirmatory colonoscopy. Despite the near curative nature of early clinical stage surgical resection, mortality remains unacceptably high-as the majority of patients diagnosed by faecal haemoglobin followed by colonoscopy occur at latter stages. Additionally, current population-based screens reliant on fecal occult blood test (FOBT) have low compliance (~ 40%) and tests suffer low sensitivities. Therefore, blood-based diagnostic tests offer survival benefits from their higher compliance (≥ 97%), if they can at least match the sensitivity and specificity of FOBTs. However, discovery of low abundance plasma biomarkers is difficult due to occupancy of a high percentage of proteomic discovery space by many high abundance plasma proteins (e.g., human serum albumin). Methods:A combination of high abundance protein ultradepletion (e.g., MARS-14 and an in-house IgY depletion columns) strategies, extensive peptide fractionation methods (SCX, SAX, High pH and SEC) and SWATH-MS were utilized to uncover protein biomarkers from a cohort of 100 plasma samples (i.e., pools of 20 healthy and 20 stages I-IV CRC plasmas). The differentially expressed proteins were analyzed using ANOVA and pairwise t-tests (p < 0.05; fold-change > 1.5), and further examined with a neural network classification method using in silico augmented 5000 patient datasets. Results:Ultradepletion combined with peptide fractionation allowed for the identification of a total of 513 plasma proteins, 8 of which had not been previously reported in human plasma (based on PeptideAtlas database). SWATH-MS analysis revealed 37 protein biomarker candidates that exhibited differential expression across CRC stages compared to healthy controls. Of those, 7 candidates (CST3, GPX3, CFD, MRC1, COMP, PON1 and ADAMDEC1) were validated using Western blotting and/or ELISA. The neural network classification narrowed down candidate biomarkers to 5 proteins (SAA2, APCS, APOA4, F2 and AMBP) that had maintained accuracy which could discern early (I/II) from late (III/IV) stage CRC. Conclusion:MS-based proteomics in combination with ultradepletion strategies have an immense potential of identifying diagnostic protein biosignature.

Project description:ImportanceThere is mixed evidence that blood pressure (BP) stabilizes or decreases in later life. It is also unclear whether BP trajectories reflect advancing age, proximity to end of life, or selective survival of persons free from hypertension.ObjectiveTo estimate individual patient BP for each of the 20 years before death and identify potential mechanisms that may explain trajectories.Design, study, and participantsWe analyzed population-based Clinical Practice Research Datalink primary care and linked hospitalization electronic medical records from the United Kingdom, using retrospective cohort approaches with generalized linear mixed-effects modeling. Participants were all available individuals with BP measures over 20 years, yielding 46 634 participants dying aged at least 60 years, from 2010 to 2014. We also compared BP slopes from 10 to 3 years before death for 20 207 participants who died, plus 20 207 birth-year and sex-matched participants surviving longer than 9 years.Main outcomes and measuresClinically recorded individual patient repeated systolic BP (SBP) and diastolic BP (DBP).ResultsIn 46 634 participants (51.7% female; mean [SD] age at death, 82.4 [9.0] years), SBPs and DBPs peaked 18 to 14 years before death and then decreased progressively. Mean changes in SBP from peak values ranged from -8.5 mm Hg (95% CI, -9.4 to -7.7) for those dying aged 60 to 69 years to -22.0 mm Hg (95% CI, -22.6 to -21.4) for those dying at 90 years or older; overall, 64.0% of individuals had SBP changes of greater than -10 mm Hg. Decreases in BP appeared linear from 10 to 3 years before death, with steeper decreases in the last 2 years of life. Decreases in SBP from 10 to 3 years before death were present in individuals not treated with antihypertensive medications, but mean yearly changes were steepest in patients with hypertension (-1.58; 95% CI, -1.56 to -1.60 mm Hg vs -0.70; 95% CI, -0.65 to -0.76 mm Hg), dementia (-1.81; 95% CI, -1.77 to -1.87 mm Hg vs -1.41; 95% CI, -1.38 to -1.43 mm Hg), heart failure (-1.66; 95% CI, -1.62 to -1.69 mm Hg vs -1.37; 95% CI, -1.34 to -1.39 mm Hg), and late-life weight loss.Conclusions and relevanceMean SBP and DBP decreased for more than a decade before death in patients dying at 60 years and older. These BP decreases are not simply attributable to age, treatment of hypertension, or better survival without hypertension. Late-life BP decreases may have implications for risk estimation, treatment monitoring, and trial design.

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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.

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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.

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