ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Serum PEA Uncovers Novel Diagnostic Biomarkers for Colorectal Cancer
Provisionally accepted
- The Fourth Hospital of Harbin Medical University, Harbin, China
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Abstract. Colorectal cancer (CRC) is one of the predominant life-threatening malignancies, with early diagnosis remaining challenging due to its multifaceted pathophysiologic mechanism of development. Proteome analysis using proximity extension assay (PEA) based on Olink technology expands the diagnostic horizon and the discovery of rare proteins essential in disease pathogenesis. In the current study, the expression levels of 92 oncology-related proteins were assessed in CRC patients (n=15) and healthy individuals (n=16) using the Olink technology. Among 92 cancer-associated proteins, 19 proteins with differential expression (DEP) between CRC and healthy individuals were identified. Bioinformatic analysis of the DEPs revealed that the cytoplasm, IL-1-mediated, and MAPK signaling pathways emerged as the most prominently represented Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, the levels of CBLN4, HSPB6, and SPINK4 were validated via enzyme-linked immunosorbent assay (ELISA) in CRC (n=94) compared with healthy control (n=90) serum, with cut-off values of 2.3 ng/ml, 15.2 ng/ml, and 7.4 ng/ml, respectively. The results showed that HSPB6 and SPINK4 levels were significantly higher in the rectum location group than in the colon location group (p=0.034 and p=0.024, respectively), and CBLN4 levels were significantly lower in the early stage of tumor progression group than in late stage of tumor progression group (p=0.017). The biomarker combination of CBLN4 and HSPB6 demonstrated significant diagnostic potential with an area under the ROC curve of 0.93 and high diagnostic accuracy with a sensitivity and specificity of 93% and 78%, respectively. Through Olink protein profiling, this study enhances the current understanding of the molecular mechanisms underlying colorectal cancer, offering innovative methods for early diagnosis and potential treatment.
Keywords: Cbln4, colorectal cancer, HSPB6, PEA, Spink4
Received: 03 Nov 2025; Accepted: 18 Dec 2025.
Copyright: © 2025 Glazutdinova, Liu, Huang, Zhang, Ji, Wu, Gao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yu Liu
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