Identification of Novel Plasma Protein Biomarkers for Early Clinical Stage Colorectal Carcinoma by High-Throughput Proteomics
5 affiliations
- 1State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China
- 2Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
- 3Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin Institute of Coloproctology, Tianjin 300121, China
- 4Tianjin Union Medical Center, Nankai University, Tianjin 300071, China
- 5Haihe Laboratory of Cell Ecosystem, Tianjin 300020, China
Abstract
Early detection is critical for improving survival in colorectal carcinoma (CRC), underscoring the need for reliable early-stage biomarkers. Plasma protein biomarkers may support the detection of early-stage CRC. In this study, we profiled plasma from 24 patients with stages I–III CRC and 10 non-tumor participants, together with paired tumor and distant-normal tissues from the patients with CRC, to identify proteins preferentially elevated in stage I disease. Seven plasma proteins had higher abundance in stage I CRC than in stages II and III CRC and non-tumor participants; three of these proteins, HSPA8, ALDOA, and PDLIM1, were also elevated in stage I tumor tissues. In the discovery comparison of stage I CRC with non-tumor participants, HSPA8 alone achieved an internally cross-validated random forest classification accuracy of 88.9%, matching the three-protein model. Tissue upregulation was further supported by Western blotting. ELISA assessment included 32 participants with matched proteomic measurements and was subsequently expanded to 108 participants. The HSPA8-score was calculated by dividing the dilution-corrected HSPA8 concentration by the total protein amount in 10 μL of plasma. In the expanded cohort, random forest classification using this score achieved internally cross-validated accuracies of 74.47% for stage I versus stages II–IV CRC and 56.67% for stage I CRC versus non-tumor participants. The corresponding exploratory reference cutoffs were 0.066 and 0.029. These findings identify HSPA8 as a potential plasma protein biomarker for stage I CRC detection.
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BibTeX
@article{yin2026identification,
title = {{Identification of Novel Plasma Protein Biomarkers for Early Clinical Stage Colorectal Carcinoma by High-Throughput Proteomics}},
author = {Guoxing Yin and Zhifei Chen and Guofeng Feng and Jiangtao Lu and Chenmeng Jiao and Zhengmao Zhu and Lin Liu and Chen Xu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219630},
url = {https://www.mdpi.com/1422-0067/27/21/9630},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Identification of Novel Plasma Protein Biomarkers for Early Clinical Stage Colorectal Carcinoma by High-Throughput Proteomics
AU - Guoxing Yin
AU - Zhifei Chen
AU - Guofeng Feng
AU - Jiangtao Lu
AU - Chenmeng Jiao
AU - Zhengmao Zhu
AU - Lin Liu
AU - Chen Xu
PY - 2026
DA - 2026/10/28
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219630
UR - https://www.mdpi.com/1422-0067/27/21/9630
AB - Early detection is critical for improving survival in colorectal carcinoma (CRC), underscoring the need for reliable early-stage biomarkers. Plasma protein biomarkers may support the detection of early-stage CRC. In this study, we profiled plasma from 24 patients with stages I–III CRC and 10 non-tumor participants, together with paired tumor and distant-normal tissues from the patients with CRC, to identify proteins preferentially elevated in stage I disease. Seven plasma proteins had higher abundance in stage I CRC than in stages II and III CRC and non-tumor participants; three of these proteins, HSPA8, ALDOA, and PDLIM1, were also elevated in stage I tumor tissues. In the discovery comparison of stage I CRC with non-tumor participants, HSPA8 alone achieved an internally cross-validated random forest classification accuracy of 88.9%, matching the three-protein model. Tissue upregulation was further supported by Western blotting. ELISA assessment included 32 participants with matched proteomic measurements and was subsequently expanded to 108 participants. The HSPA8-score was calculated by dividing the dilution-corrected HSPA8 concentration by the total protein amount in 10 μL of plasma. In the expanded cohort, random forest classification using this score achieved internally cross-validated accuracies of 74.47% for stage I versus stages II–IV CRC and 56.67% for stage I CRC versus non-tumor participants. The corresponding exploratory reference cutoffs were 0.066 and 0.029. These findings identify HSPA8 as a potential plasma protein biomarker for stage I CRC detection.
SN - 1422-0067
ER -