Abstract 524P
Background
Aggressive cancers lacking standard screening tests (LSST) constitute 60% new cases and are responsible for 70% death cases due to late-stage status diagnosis. Blood tests detecting circulating tumor DNA have emerged as a promising approach for multi-cancer early detection. We developed a multimodal test, Screening for the Presence Of Tumor by Methylation And Size (SPOT-MAS), to analyze methylomic and fragmentomic profiles of plasma cell-free DNA (cfDNA). This assay was validated in a case-control study of 738 cancer patients with common cancers (breast, colorectal, liver, lung and gastric). Here, we extend this approach to identify cancer-specific methylation and fragment length markers from LSST cancers and evaluate the performance of SPOT-MAS in detecting these samples.
Methods
We recruited 739 healthy samples and 111 patients across five LSST cancers—endometrial, esopheageal, head neck, ovarian, and pancreatic. Using SPOT-MAS workflow, we profiled cfDNA methylation and fragmentomic patterns to identify distinctive signatures for each cancer type and assessed the accuracy in detecting these samples.
Results
There were 372 differentially methylated regions (DMRs) identified between LSST cancers and control, 356 of which overlapped with DMRs found in five common cancers, indicating universal methylation patterns among different cancers. Moreover, LSST cancers exhibited a genome-wide hypomethylation pattern. Fragment profiles of these cancers deviated from controls, with esophageal and head neck cancers showing enrichment in short cfDNA fragments (<150 bp). We found eight 4-mer end motifs consistently differed in cfDNA fragments from LSST and common cancers. Our assay achieved a specificity of 96.2% and an overall sensitivity of 77.5% (68%, 73%, 83%, 84%, and 86% for head neck, ovarian, pancreatic, esophageal and endometrial, respectively). Sensitivity for early-stage, non-metastatic cancers was 71%, increasing to 85% for metastatic stages.
Conclusions
SPOT-MAS offers a non-invasive method for detecting multiple cancers, including those lacking standard screening tests. Further validation in larger cohorts is warranted to substantiate the efficacy of SPOT-MAS in identifying various cancer types.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Medical Genetics Institute, Vietnam.
Funding
Gene Solutions, Vietnam.
Disclosure
All authors have declared no conflicts of interest.