Abstract 1232P
Background
Many cancers are symptoms free in early clinical stages, causing nearly half of patients diagnosed in advanced-stages when therapeutic options are limited. Early cancer detection is key to improve clinical outcomes. We developed PanSeer7, a multi-cancer detection assay based on targeted bisulfite sequencing of circulating cell-free DNA (cfDNA) and evaluated its technical performances of reproducibility and sensitivity.
Methods
The PanSeer7 panel consists of 2,447 markers which are either differentially methylated between healthy and cancer samples, or distinctively methylated in a specific cancer. We assessed its reproducibility by sequencing 40 technical replicates of synthetic healthy cfDNA samples on 4 independent batches and with different inputs (2∼20 ng). For its limit of detection (LOD), we prepared samples mimicking cancer plasma DNA by diluting fragmented cancer cell line DNA, from 7 common cancer types, into GM12878 control at ratios of 1/10,000 to 1/100. We tested PanSeer7’s ability to identify tissue of origin (TOO) by analyzing DNA from formalin-fixed paraffin-embedded (FFPE) tissues and healthy plasma.
Results
PanSeer7 produced highly consistent methylation levels among replicates at a minimum of 10 ng input. Its technical LOD was 1/10,000 for lung cancer (LuC; H1650), liver cancer (LiC; HepG2), gastric cancer (GC; HGC27), esophageal cancer (EC; KYSE150) and colorectal cancer (CC; SW480), and slightly lower as 5/10,000 for pancreatic cancer (PC; PANC1) and breast cancer (BC; MDA-MB-231). To evaluate PanSeer7’s accuracy for predicting TOO, we sequenced 38 healthy plasma and 121 FFPE tissues (17 LiC, 13 PC, 21 GC, 18 EC, 16 CC, 14 LuC and 22 BC). They were clearly clustered according to their TOO based on methylation levels. We simulated 3,500 datasets by mixing reads of cancer tissue into those of healthy plasma at ratios of 1/10,000 to 1/100, and the TOO-predicting model achieved an accuracy over 95% at a ratio of 5/10,000.
Conclusions
With excellent technical performances in both cancer detection and TOO identification, PanSeer7 is promising to be clinically applied for non-invasive multi-cancer detection.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Sun, M. Su, M. Xu, J. Ma, Q. He, Z. Su: Financial Interests, Personal, Full or part-time Employment: Singlera Genomics Inc. R. Liu: Financial Interests, Personal, Officer: Singlera Genomics Inc. All other authors have declared no conflicts of interest.
Resources from the same session
1774P - PC-PEP, a comprehensive daily six-month home-based prostate cancer: Patient empowerment program improves quality of life, physical fitness, and urinary function outcomes among prostate cancer patients with localized disease - Secondary analyses of a randomized clinical trial
Presenter: Gabriela Ilie
Session: Poster session 14
1775P - A newly-developed deep-learning algorithm: NAFNet outperforms ResNet50 for predicting adverse pathology events and biochemical recurrence time using MRI from prostate cancer patients
Presenter: Zheng Liu
Session: Poster session 14
1776P - Body composition in adult life and prostate cancer (PCa) incidence and mortality: The PROCA-life study
Presenter: Martin Støyten
Session: Poster session 14
1777P - Enzalutamide (enza) monotherapy for the treatment (tx) of prostate cancer with high-risk biochemical recurrence (BCR): EMBARK secondary endpoints
Presenter: Ugo De Giorgi
Session: Poster session 14
1778P - Treatment (tx) of high-risk biochemically recurrent prostate cancer with enzalutamide (enza) in combination with leuprolide acetate (LA): Secondary endpoints from EMBARK
Presenter: Stephen Freedland
Session: Poster session 14
1779P - PSMA guided approach for bIoCHEmical relapse after prostatectomy-PSICHE trial
Presenter: Giulio Francolini
Session: Poster session 14
1780P - The health inequality impact of darolutamide for non-metastatic castration-resistant prostate cancer: A distributional cost-effectiveness analysis
Presenter: Jeroen Jansen
Session: Poster session 14
1782P - Prostate radiotherapy reduces long-term risk of obstructive uropathy in metastatic hormone sensitive prostate cancer (mHSPC): Results from the STAMPEDE M1|RT comparison
Presenter: Craig Jones
Session: Poster session 14
1783P - PROSTRATEGY: A SOGUG randomized trial of androgen deprivation therapy (ADT) plus docetaxel (dct) +/- nivolumab (nivo) or ipilimumab-nivolumab (ipi-nivo) in high-volume metastatic hormone-sensitive prostate cancer (hvHSPCa) - Efficacy results from the pilot phase
Presenter: Jose Arranz Arija
Session: Poster session 14