Core Viewpoint - The article discusses a groundbreaking study published in Cell Research that establishes a novel model for detecting multiple cancers using residual DNA in red blood cells (rbcDNA), enabling early cancer detection through a non-invasive blood test [1][10]. Group 1: Research Background - Cancer is the second leading cause of death globally, with increasing incidence and mortality rates. Early detection significantly improves survival rates, yet most cancers are diagnosed at advanced stages due to a lack of effective screening methods [3]. - Liquid biopsy technologies, particularly those based on circulating free DNA (cfDNA) and circulating tumor DNA (ctDNA), show promise for non-invasive cancer detection. However, challenges such as limited ctDNA in early cancers and interference from somatic mutations in non-cancerous tissues highlight the need for more stable and reliable biomarkers [3][4]. Group 2: Study Findings - The research analyzed 412 samples (236 healthy individuals and 174 early-stage colorectal cancer patients) and demonstrated that only 1-2 mL of peripheral blood is required for the detection process, making it a convenient and non-invasive solution for early cancer detection [7][10]. - The study identified significant genomic differences in rbcDNA between early-stage cancer patients and healthy individuals, suggesting the potential of rbcDNA as a high-precision biomarker for early cancer detection [4][10]. Group 3: Technical Advantages - The study introduces rbcDNA as a new biomarker for liquid biopsy, offering several advantages: low sample volume (1-2 mL), high stability (rbcDNA is less prone to degradation), and longer average length (4253 bp compared to cfDNA's 167 bp) [10][11]. - The research established a global rbcDNA genomic atlas and identified 246 characteristic DNA regions in colorectal cancer patients, with 86% of these regions significantly differing from healthy individuals [10]. - An AI diagnostic model was developed using 16 key regions, achieving a sensitivity of 94% for early colorectal cancer detection and an overall sensitivity of 93% for multiple cancer types, with a specificity of 96% [10][11]. Group 4: Mechanism Insights - The study revealed that tumors can manipulate bone marrow hematopoietic stem cells, driving the formation of rbcDNA characteristics. This manipulation is linked to the secretion of IL-18, which activates key transcription factors and promotes chromosomal instability [10][11]. - It was noted that sustained inflammation is necessary for triggering rbcDNA characteristics, indicating that short-term inflammation does not have the same effect [10].