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Comprehensive aptamer-based screen of 1317 proteins uncovers improved stool protein markers of colorectal cancer

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Abstract

Background

To screen and validate novel stool protein biomarkers of colorectal cancer (CRC).

Methods

A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets.

Results

A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis.

Conclusions

Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.

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Acknowledgements

H.L. was supported by the China Scholarship Council (CSC). The authors would like to acknowledge the technical help rendered by Janet Yao and Patricia Jeraldo (Mayo Clinic). We also acknowledge the pioneering work of Dr. David Ahlquist in building up the Mayo stool bank.

Author information

Author notes

  1. Hao Li and Kamala Vanarsa both authors contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

    Hao Li & Huanlong Qin

  2. Department of Biomedical Engineering, University of Houston, Houston, USA

    Hao Li, Kamala Vanarsa, Ting Zhang, Sanam Soomro, Pietro Antonio Cicalese, Valeria Duran, Shobha Dasari & Chandra Mohan

  3. Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School, UT Health Science Center At Houston, Houston, USA

    Kyung Hyun Lee & Claudia Pedroza

  4. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, USA

    John B. Kisiel

  5. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA

    Robert S. Bresalier

  6. Department of Surgical Research, Mayo Clinic, Rochester, USA

    Nicholas Chia

Authors
  1. Hao Li
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Contributions

Study concept, design, data interpretation: CM, Acquisition and analysis of data, establishment of methodology: HL, KV, TZ, SS, PAC, VD, SD, KHL, CP, JBK, HQ, RSB, NC. All authors read and approved the manuscript.

Corresponding author

Correspondence to Chandra Mohan.

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Ethical standards

The study was approved by the respective ethics boards of the Mayo Clinic (IRB# 16-003882) and the University of Houston (IRB#15192-EX).

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Li, H., Vanarsa, K., Zhang, T. et al. Comprehensive aptamer-based screen of 1317 proteins uncovers improved stool protein markers of colorectal cancer. J Gastroenterol 56, 659–672 (2021). https://doi.org/10.1007/s00535-021-01795-y

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  • DOI: https://doi.org/10.1007/s00535-021-01795-y

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