Communications medicine · 2026
Patient-specific alterations in blood plasma cfRNA profiles enable accurate classification of cancer patients and controls.
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Morlion Annelien, Decruyenaere Philippe, Schoofs Kathleen, Anckaert Jasper, Johns Ramirez Nickolas, Nuytens Justine, Vanden Eynde Eveline, Verniers Kimberly, Everaert Celine, Brusselle Guy, Callens Steven, Haerynck Filomeen, Hemelsoet Dimitri, Hoste Eric, Lambert Jo, Lumen Nicolaas, Offner Fritz, Paemeleire Koen, Smith Vanessa, Van den Eynde Lies, Van Dorpe Jo, Vanhaecke Amber, Van Vlierberghe Hans, Mariman An, Thas Olivier, Vandesompele Jo, Mestdagh Pieter
Аннотация
BACKGROUND: Circulating nucleic acids in blood plasma form an attractive, minimally invasive resource to study human health and disease. In this study, we aimed to identify cell-free RNA alterations that can distinguish cancer patients from cancer-free individuals.
METHODS: We first performed mRNA capture sequencing on 266 blood plasma samples from cancer patients and controls, including a discovery set of 208 donors across 25 cancer types and a replication set of 58 donors across three cancer types. We first conducted group-level comparisons and then compared individual patient profiles to a reference control population in a one-versus-many approach. This approach was further evaluated in independent cohorts: a prostate cancer plasma cohort (n = 180), a non-malignant disease plasma cohort (n = 125), a lymphoma plasma cohort (n = 65), and a bladder cancer urine cohort (n = 24), each including both patients and controls.
RESULTS: Here we show that cancer patients exhibit both cancer type-specific and general cell-free RNA alterations. However, differentially abundant RNAs vary widely among patients and across cohorts, hampering robust biomarker identification. By comparing individual patient profiles to control populations, we identify so-called biomarker tail genes, which strongly deviate from controls. The number of these genes per sample distinguishes cancer patients from control samples. Independent cohorts also confirm the potential of this approach.
CONCLUSIONS: Our findings demonstrate substantial heterogeneity in cell-free RNA alterations among cancer patients and propose that patient-specific changes can be exploited for classification.
METHODS: We first performed mRNA capture sequencing on 266 blood plasma samples from cancer patients and controls, including a discovery set of 208 donors across 25 cancer types and a replication set of 58 donors across three cancer types. We first conducted group-level comparisons and then compared individual patient profiles to a reference control population in a one-versus-many approach. This approach was further evaluated in independent cohorts: a prostate cancer plasma cohort (n = 180), a non-malignant disease plasma cohort (n = 125), a lymphoma plasma cohort (n = 65), and a bladder cancer urine cohort (n = 24), each including both patients and controls.
RESULTS: Here we show that cancer patients exhibit both cancer type-specific and general cell-free RNA alterations. However, differentially abundant RNAs vary widely among patients and across cohorts, hampering robust biomarker identification. By comparing individual patient profiles to control populations, we identify so-called biomarker tail genes, which strongly deviate from controls. The number of these genes per sample distinguishes cancer patients from control samples. Independent cohorts also confirm the potential of this approach.
CONCLUSIONS: Our findings demonstrate substantial heterogeneity in cell-free RNA alterations among cancer patients and propose that patient-specific changes can be exploited for classification.