Composite proteomic and metabolomic plasma biomarkers for detection of colorectal, lung and ovarian cancers.
[BACKGROUND] Sensitive and specific blood biomarkers for early detection of colorectal (CRC), lung (LuCa) and ovarian (OvCa) cancers are highly warranted.
- 연구 설계 case-control
APA
Ögren JÅ, Ekström J, et al. (2026). Composite proteomic and metabolomic plasma biomarkers for detection of colorectal, lung and ovarian cancers.. Molecular cancer, 25(1). https://doi.org/10.1186/s12943-026-02654-1
MLA
Ögren JÅ, et al.. "Composite proteomic and metabolomic plasma biomarkers for detection of colorectal, lung and ovarian cancers.." Molecular cancer, vol. 25, no. 1, 2026.
PMID
41943016
Abstract
[BACKGROUND] Sensitive and specific blood biomarkers for early detection of colorectal (CRC), lung (LuCa) and ovarian (OvCa) cancers are highly warranted. The current blood tests often need to be complemented with other clinical methods to achieve adequate diagnostic performance. Recent progress in the molecular profiling of plasma from cancer patients holds potential for improved non-invasive screening. Here, we aimed to identify composite proteomic and metabolomic plasma biomarkers for early cancer detection with performances that exceed those of existing FDA-approved blood and stool-based diagnostic tests for CRC, LuCa and OvCa.
[METHODS] In a case-control study using samples from the U-CAN and EpiHealth biobanks, we measured plasma levels of 165 proteins and 244 metabolites in 818 patients with CRC, LuCa and OvCa at diagnosis, 119 patients with non-malignant conditions of the corresponding organs, and 1,129 healthy individuals. We performed an exhaustive search over all cut-off values of the ROC for all combinations of up to 4 proteins and metabolites, implementing measures to minimize the impact of cross-cohort comparisons. Ultimately, we benchmarked candidate biomarkers performance to FDA approved blood tests in clinical use for detection of cancer. External validation was performed using publicly available datasets.
[RESULTS] We found biomarkers composed of 2–4 proteins separating cases of each tumor type from healthy controls with ROC AUC, respectively for CRC: CEACAM5, FLT1, IL19, Ferritin (AUC 0.89), LuCa: FNDC5, MDK, PLAUR, CEACAM5 (AUC 0.91) and OvCa: MUC16/CA125, PLG (AUC 0.97). The diagnostic performance of these biomarkers was comparable to, and in some instances surpassed, the performance of established tests, such as Epi proColon (AUC 0.82) and Cologuard (AUC 0.93). Metabolites were informative for tumor stage discrimination, especially in LuCa and OvCa. External validation in the CancerSeek dataset showed strong agreement in biomarker performance.
[CONCLUSIONS] The composite protein biomarkers identified in this study represent a novel opportunity for detection, staging and differential diagnosis of common tumor types. Metabolites are more relevant for tumor staging than early detection. A limited number of well-performing analytes enables cost-effective implementation in clinical diagnostics and merits further evaluation.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12943-026-02654-1.
[METHODS] In a case-control study using samples from the U-CAN and EpiHealth biobanks, we measured plasma levels of 165 proteins and 244 metabolites in 818 patients with CRC, LuCa and OvCa at diagnosis, 119 patients with non-malignant conditions of the corresponding organs, and 1,129 healthy individuals. We performed an exhaustive search over all cut-off values of the ROC for all combinations of up to 4 proteins and metabolites, implementing measures to minimize the impact of cross-cohort comparisons. Ultimately, we benchmarked candidate biomarkers performance to FDA approved blood tests in clinical use for detection of cancer. External validation was performed using publicly available datasets.
[RESULTS] We found biomarkers composed of 2–4 proteins separating cases of each tumor type from healthy controls with ROC AUC, respectively for CRC: CEACAM5, FLT1, IL19, Ferritin (AUC 0.89), LuCa: FNDC5, MDK, PLAUR, CEACAM5 (AUC 0.91) and OvCa: MUC16/CA125, PLG (AUC 0.97). The diagnostic performance of these biomarkers was comparable to, and in some instances surpassed, the performance of established tests, such as Epi proColon (AUC 0.82) and Cologuard (AUC 0.93). Metabolites were informative for tumor stage discrimination, especially in LuCa and OvCa. External validation in the CancerSeek dataset showed strong agreement in biomarker performance.
[CONCLUSIONS] The composite protein biomarkers identified in this study represent a novel opportunity for detection, staging and differential diagnosis of common tumor types. Metabolites are more relevant for tumor staging than early detection. A limited number of well-performing analytes enables cost-effective implementation in clinical diagnostics and merits further evaluation.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12943-026-02654-1.