bims-fragic 2025-03-23 papers

Issue of 2025–03–23
three papers selected by
Laura Mannarino, Humanitas Research

Cancer Res Commun. 2025 Mar 18.

A Blood-based Assay for Detection of Patients with Advanced Adenomas.

Screening for colorectal cancer (CRC) with blood-based testing should detect advanced adenomas (AAs), facilitating more effective cancer prevention. We evaluated four different methods to detect AAs in plasma: (a) a machine-learning algorithm, SignaL (Signatures of fragment Length), based on cell-free DNA (cfDNA) fragmentation; (b) a "Protein-17" assay measuring 17 cancer-associated proteins; (c) a Global Aneuploidy Score (GAS); and (d) cfDNA mutation analysis querying 15 genes commonly mutated in CRC. Existing data from study populations with and without cancer were utilized to determine 99.5% specificity thresholds. We studied 40 AA cases and 32 colonoscopy-negative controls. SignaL detected 9/40 AAs (22.5%, 95%CI: 12.3-37.5%) at 100% specificity (95%CI: 89.3-100%). Protein-17 detected 5/40 AAs (12.5%, 95%CI: 5.5-26.1%) including three cases not identified by SignaL, at 100% specificity (95%CI: 89.3 to 100%). GAS detected 11/40 AAs (27.5%, 95%CI: 16.1-42.8%), but resulted in 2/32 positive controls (93.8% specificity, 95%CI: 79.9-98.3%). Combining SignaL, the Protein-17 assay, and GAS at the 99.5% specificity thresholds resulted in detection of 16/40 AAs (40%, 95% CI:26.3-55.4%) at 93.8% specificity (95% CI: 79.9% to 98.3%). Of 32/40 evaluable AA plasma samples, only one was cfDNA mutation positive at 0.01 level of significance. A blood-based assay based on the analysis of repeated sequence elements plus proteins appears to be able to detect a considerable fraction of patients with AA at relatively high specificity. Large, prospective studies are required to determine whether this approach can add to the options currently available for screening patients for pre-malignant lesions of the colon.

DOI: https://doi.org/10.1158/2767-9764.CRC-24-0398

Hum Genomics. 2025 Mar 18. 19(1): 27

Dynamic profiling of Cell-free DNA fragmentation uncovers postprandial metabolic and immune alterations.

Ziting Zhu, Tao Chen, Manting Zhang, Xiaodi Shi, Pan Yu, Jianai Liu, Xiuzhi Duan, Zhihua Tao, Xuchu Wang.

BACKGROUND: Food intake affects body homeostasis and significantly changes circulating cell-free DNA (cfDNA). However, the source and elimination of postprandial cfDNA is difficult to trace, and it is unknown whether these changes can be revealed by cfDNA fragmentomics based on liquid biopsy.
METHODS: We performed shallow whole-genome sequencing of 30 plasma samples from 10 healthy individuals at fasting and postprandial (30-min and 2-h time points). We assessed the effect of postprandial states on cfDNA fragment size distribution and utilized deconvolutional analysis of end motifs to determine the potential roles of DNA nucleases in cfDNA fragmentation. We correlated the fragmentation index (defined as the ratio of short-to-long fragments) with gene expression to estimate the relative contribution of various cellular and tissue sources to cfDNA.
RESULTS: Compared to the fasting state, we observed a significant increase in short cfDNA fragments (70-150 bp) and a decrease in long fragments (151-250 bp) at the 30-minute postprandial state, followed by an inverse trend two hours later. Deconvolutional analysis of cfDNA end motifs showed that DNASE1L3 activity decreased at the 30-minute postprandial state, while DNASE1 and DFFB activities increased at the 2-hour postprandial state. We found that the expression of genes related to cellular metabolism and immune responses was upregulated at the postprandial state. Meanwhile, the contribution of cells and tissues involved in metabolic and immune progress to circulating plasma cfDNA was increased.
CONCLUSIONS: The fragmentation of cfDNA is considerably influenced by postprandial states, highlighting the significance of taking postprandial effects into account when evaluating cfDNA as a biomarker. Furthermore, our study reveals the potential application of cfDNA fragmentation features in monitoring metabolic and immune status changes.

Keywords: Cell-free DNA; CfDNA fragmentation; Immune response; Liquid biopsy; Metabolic process; Postprandial effects

DOI: https://doi.org/10.1186/s40246-025-00739-4

Front Oncol. 2025 ;15 1520869

Evaluation of an innovative multi-cancer early detection test: high sensitivity and specificity in differentiating cancer, inflammatory conditions, and healthy individuals.

Nike Walter, Jörg Groth, Berthold von Und Zu Zwerger.

Background: Cancer is a leading cause of death worldwide, with early detection crucial for effective treatment. Traditional diagnostic methods, such as imaging and biopsies, are often limited by invasiveness, cost, and sensitivity. Blood-based multi-cancer early detection (MCED) tests offer a less invasive and potentially more comprehensive approach. Recently, a novel screening tool, the Carcimun® test was reported, detecting conformational changes in plasma proteins through optical extinction measurements. This study evaluates the Carcimun® test's performance, including participants with inflammatory conditions.
Methods: This prospective, single-blinded study included 172 participants: 80 healthy volunteers, 64 cancer patients (various types), and 28 individuals with inflammatory conditions (fibrosis, sarcoidosis, pneumonia) or benign tumors. Plasma samples were analyzed using the Carcimun® test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.
Results: Mean extinction values were significantly higher in cancer patients (315.1) compared to healthy individuals (23.9) and those with inflammatory conditions (62.7) (p<0.001). The Carcimun® test distinguished these groups with high accuracy (95.4%), sensitivity (90.6%), and specificity (98.2%). Significant differences were found between healthy participants and cancer patients (p<0.001), and between cancer patients and those with inflammation (p<0.001).
Conclusion: The Carcimun® test achieved high accuracy, sensitivity, and specificity, effectively identifying cancer patients while minimizing false positives and negatives. By including participants with inflammatory conditions, we addressed a significant limitation of previous studies, demonstrating the test's robustness in real-world clinical scenarios. These findings underscore the potential of the Carcimun® test as a valuable tool for early cancer detection and screening.

Keywords: cancer screening; diagnostic; liquid biopsy; multi-cancer early detection; plasma protein test

DOI: https://doi.org/10.3389/fonc.2025.1520869