PO.CL01.18 · 临床研究

Epigenetic profiling identifies markers of aggressive cancer subtype using a targeted methylation-based multi-cancer early detection (MCED) blood test

海报缩略图：Epigenetic profiling identifies markers of aggressive cancer subtype using a targeted methylation-based multi-cancer early detection (MCED) blood test

编号 1100 展板 10 时间 4/19 02:00–05:00 区域 Section 43 主讲 Yue An, BS;MS

分会场 Early Detection Biomarkers 1

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作者与单位

Kezhong Chen¹, Jian Huang², Dahong Zhang³, Shu Wang⁴, Hongxu Liu⁵, Wenzhao Zhong⁶, Xiangnan Li⁷, Qiang Zhang⁵, Zhigao Li⁸, Jiaqi Liu⁹, Ziqing Tian¹⁰, Fei Zhou¹¹, Gongsheng Jin¹², Xudong Xiang¹³, Zhigang Li¹⁴, Hui Xie¹⁵, Ya Wei¹⁶, Guochun Zhang¹⁷, Guolin Ye¹⁸, Ming Cai¹⁹, Junfeng Wang⁸, Yan Zhang²⁰, Chao Cheng²¹, Hefei Li²², Desong Yang²³, Jianhong Lian²⁴, Sheng Huang²⁵, Tao Xu²⁶, Zengjun Wang²⁷, Xi Guo²⁸, Zhuowei Liu²⁹, Minfeng Chen³⁰, Yang Wang³¹, Yue An³¹, Yanzhan Yang³¹, Min Li³¹, Jing Liu³¹, Baoliang Zhu³¹, Yonghui Li³¹, Xiaohui Wu³¹, Fan Yang¹, Jun Wang¹

¹Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, China,²The Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,³Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China,⁴Breast Disease Center, Peking University People's Hospital, Beijing, China,⁵Liaoning Provincial Cancer Hospital, Shenyang, China,⁶Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China,⁷The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China,⁸Harbin Medical University Cancer Hospital, Harbin, China,⁹Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,¹⁰Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China,¹¹Shanghai Pulmonary Hospital, Shanghai, China,¹²The First Affiliated Hospital of Bengbu Medical College, Bengbu, China,¹³Department of Thoracic Surgery, Yunnan Cancer Hospital, Kunming, China,¹⁴Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicine, Shanghai, China,¹⁵Department of Breast Cancer Research Center, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China,¹⁶Anyang Tumor Hospital, Anyang, China,¹⁷Department of Breast Surgery, Guangdong Provincial People's Hospital, Guangzhou, China,¹⁸Department of Breast Cancer, The First People's Hospital of Foshan, Foshan, China,¹⁹Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,²⁰Department of Oncology, Shijiazhuang People’s Hospital, Shijiazhuang, China,²¹Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,²²Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, China,²³Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China,²⁴Department of General Surgery,Shanxi Cancer Hospital, Taiyuan, China,²⁵Department of Breast Surgical Oncology,Yunnan Cancer Hospital, Kunming, China,²⁶Peking University People's Hospital, Beijing, China,²⁷Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China,²⁸Department of Urology, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, China,²⁹Sun Yat-sen University Cancer Center, Guangzhou, China,³⁰Department of urology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China,³¹Shanghai Xiaohe Medical Laboratory Co. Ltd., Shanghai, China

摘要 Abstract

Background: Previous MCED studies have shown differences in detection performance across different aggressiveness cancer subtypes. However, the methylation profiles and ctDNA shedding patterns across different aggressiveness subtypes have not been analyzed. We systematically compared cell-free DNA (cfDNA) tumor fraction and methylation profiles across aggressiveness subtypes in three cancers to identify epigenetic biomarkers that differentiate tumor aggressiveness. Methods: Blood samples from a case-control study (NCT06217900) including 757 cancer cases were analyzed using a targeted methylation-based MCED test. We compared cfDNA tumor fraction and methylation profiles between aggressiveness subtypes, stage-matched small cell lung cancer (SCLC) (n=137) versus (vs) non-small cell lung cancer (NSCLC) (n=137), stage I invasive lung adenocarcinoma (IAC) (n=81) vs minimally invasive adenocarcinoma (MIA) (n=81), triple-negative breast cancer (TNBC) (n=151) vs non-TNBC (n=151), and intermediate/high-grade prostate cancer (Gleason Grade Group[GG] 2-5)(n=14) vs low-grade prostate cancer(GG1)(n=6). Tumor fraction was estimated using zero-inflated Negative Binomial model based on the distribution of methylation signals, and methylation profiles were assessed by calculating methylated/unmethylated (M/U) ratios between different aggressiveness subtypes. Marker comparisons were conducted using the Mann-Whitney U test with multiple testing corrections. Results: The sensitivity is higher in more aggressive subtypes (lung cancer 93.73% vs SCLC 99.27%; breast cancer 70.76% vs TNBC 81.46%; prostate cancer 40% vs intermediate and high-grad prostate cancer 42.86%). In lung cancer, SCLC exhibited a significantly higher cfDNA tumor fraction than NSCLC (Wilcoxon p = 2.24×10⁻²⁴), with 41,136 markers (79.18% hypomethylated) showing elevated M/U ratios. In stage I lung adenocarcinoma, IAC demonstrated a higher cfDNA tumor fraction (Wilcoxon p = 2.55×10⁻⁶) and systematic methylation differences compared to MIA. In breast cancer, TNBC had a significantly higher cfDNA tumor fraction than non-TNBC (Wilcoxon p = 2.55×10⁻⁶), with 25,717 markers (80.32% hypomethylated) displaying increased M/U ratios. Among prostate cancers of the same stage, GG2-5 cases exhibited higher cfDNA tumor fraction (Wilcoxon p = 0.038) and systematic methylation alterations compared to GG1. Conclusion: Aggressive tumor subtypes consistently display elevated cfDNA tumor fraction and characteristic methylation profiles marked by increased M/U ratios. These findings suggest cfDNA methylation patterns are promising epigenetic biomarkers for distinguishing tumor aggressiveness, potentially improving cancer screening precision and reducing overdiagnosis.

利益披露 Disclosure

K. Chen, None.. J. Huang, None.. D. Zhang, None.. S. Wang, None.. H. Liu, None.. W. Zhong, None.. X. Li, None.. Q. Zhang, None.. Z. Li, None.. J. Liu, None.. Z. Tian, None.. F. Zhou, None.. G. Jin, None.. X. Xiang, None.. Z. Li, None.. H. Xie, None.. Y. Wei, None.. G. Zhang, None.. G. Ye, None.. M. Cai, None.. J. Wang, None.. Y. Zhang, None.. C. Cheng, None.. H. Li, None.. D. Yang, None.. J. Lian, None.. S. Huang, None.. T. Xu, None.. Z. Wang, None.. X. Guo, None.. Z. Liu, None.. M. Chen, None. Y. Wang, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. Y. An, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. Y. Yang, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. M. Li, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. J. Liu, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. B. Zhu, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. Y. Li, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. X. Wu, Shanghai Xiaohe Medical Laboratory Co. Ltd. Employment. F. Yang, None.. J. Wang, None.

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