Abstract 410P
Background
Cell-free DNA (cfDNA) fragmentation patterns hold immense potential for early cancer detection. However, the lack of systematic comparison among these patterns has impeded their broader research and practical implementation.
Methods
Here, we collected over 1,382 plasma cfDNA sequencing samples from diverse sources, covering eight cancer types including breast cancer, cholangiocarcinoma, colorectal cancer, gastric cancer, lung cancer, ovarian cancer, pancreatic cancer, and liver cancer. Considering that cfDNA within open chromatin regions is more susceptible to fragmentation, we leveraged ten fragmentation patterns within open chromatin regions as features and employed machine learning techniques to evaluate their performance. The considered fragmentation patterns included Windowed Protection Score, Preferred end coordinates, Coverage, Orientation-aware Cell-free Fragmentation, DNA Evaluation of Fragments for early Interception, Fragment Size Ratio, Fragment Size Distribution, End Motif preferences, Promoter Fragmentation Entropy, and Integrated Fragmentation Score.
Results
All fragmentation patterns demonstrated discernible classification capabilities, and the category of fragmentation patterns incorporating both fragment length and coverage information exhibited robust predictive capacities. The ensemble model integrating all these fragmentation patterns further improved performance in cancer detection and tissue-of-origin analysis. Biologically, crucial features of the model captured critical regulatory regions involved in cancer pathogenesis.
Conclusions
A comprehensive machine-learning-based evaluation of ten major cfDNA fragmentation patterns for early cancer detection was performed. Enhanced performance in cancer diagnosis and tissue-of-origin estimation was achieved, through integration of these fragmentation patterns in an ensemble model with biological interpretability.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
173P - Lenvatinib (L) versus sorafenib (S) second-line therapy in hepatocellular carcinoma (HCC) patients progressed to atezolizumab plus bevacizumab (AB)
Presenter: Mara Persano
Session: Poster Display
Resources:
Abstract
174P - Unlocking the potential of blood-based biomarkers in pancreatic cancer for early detection and therapeutic screening
Presenter: Belinda Lee
Session: Poster Display
Resources:
Abstract
175P - Genomic evolution of peritoneal metastasis in gastric adenocarcinoma
Presenter: Lan Tu
Session: Poster Display
Resources:
Abstract
176P - Identification of novel diagnostic markers for pancreatic neuroendocrine tumors by proteomics with patient blood
Presenter: HEE SEON Kim
Session: Poster Display
Resources:
Abstract
177P - Burden of stomach cancer attributable to smoking in South Asia from 1990-2019, its projection of deaths to 2040: A benchmarking and comparative analysis
Presenter: Pranay Vaghela
Session: Poster Display
Resources:
Abstract
178P - Survival benefit of splenic hilar lymph nodes (no.10) dissection in B4 type gastric carcinoma: An IPTW propensity score analysis of large multi-institutional data
Presenter: Oh Jeong
Session: Poster Display
Resources:
Abstract
179P - The impact of pre-operative nutritional/rehabilitative assessments and support on postoperative outcomes in very elderly gastric cancer patients
Presenter: Yuki Ushimaru
Session: Poster Display
Resources:
Abstract
180P - Appraisal of surgical outcomes and oncological efficiency of intraoperative adverse events in robotic radical gastrectomy for gastric cancer
Presenter: shangguan Zhixin
Session: Poster Display
Resources:
Abstract
181P - TQB2450 (PD-L1 blockade) in combination with anlotinib as a perioperative treatment for patients with hepatocellular carcinoma at high risk of recurrence: Primary results from a prospective, single-arm, phase Ib study
Presenter: Zhen Huang
Session: Poster Display
Resources:
Abstract
182P - Cytoreductive surgery and chemotherapy in metastatic gastric adenocarcinoma: A population-based study
Presenter: Dana Al Zamer
Session: Poster Display
Resources:
Abstract