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Beyond Colonoscopy: Exploring New Cell Surface Biomarkers for Detection of Early, Heterogenous Colorectal Lesions

Ramezani, Saleh, Parkhideh, Arianna, Bhattacharya, Pratip K., Farach-Carson, Mary C., Harrington, Daniel A.·2021·Frontiers in Oncology
DOI 10.3389/fonc.2021.657701PMC PMC8287259
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Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women in the United States. Early detection and surgical removal of high-risk lesions in the colon can prevent disease from developing and spreading. Despite implementation of programs aimed at early detection, screening colonoscopies fail to detect a fraction of potentially aggressive colorectal lesions because of their location or nonobvious morphology. Optical colonoscopies, while highly effective, rely on direct visualization to detect changes on the surface mucosa that are consistent with dysplasia. Recent advances in endoscopy techniques and molecular imaging permit microscale visualization of the colonic mucosa. These technologies can be combined with various molecular probes that recognize and target heterogenous lesion surfaces to achieve early, real-time, and potentially non-invasive, detection of pre-cancerous lesions. The primary goal of this review is to contextualize existing and emergent CRC surface biomarkers and assess each’s potential as a candidate marker for early marker-based detection of CRC lesions. CRC markers that we include were stratified by the level of support gleaned from peer-reviewed publications, abstracts, and databases of both CRC and other cancers. The selected biomarkers, accessible on the cell surface and preferably on the luminal surface of the colon tissue, are organized into three categories: (1) established biomarkers (those with considerable data and high confidence), (2) emerging biomarkers (those with increasing research interest but with less supporting data), and (3) novel candidates (those with very recent data, and/or supportive evidence from other tissue systems). We also present an overview of recent advances in imaging techniques useful for visual detection of surface biomarkers, and discuss the ease with which these methods can be combined with microscopic visualization.

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Figure 1 Overview of targeted imaging approaches to identifying flat colorectal lesions. For lesions that are not easily identified by traditional white light colonoscopy, a modified endoscope can both deliver high-contrast particles across tissue surfaces, and identify their retention through fluorescence barcoding, or via other sensitive visualization methods. Such “nanobeacons” could reveal otherwise undetectable early lesions.
Figure 1 Overview of targeted imaging approaches to identifying flat colorectal lesions. For lesions that are not easily identified by traditional white light colonoscopy, a modified endoscope can both deliver high-contrast particles across tissue surfaces, and identify their retention through fluorescence barcoding, or via other sensitive visualization methods. Such “nanobeacons” could reveal otherwise undetectable early lesions.CC BY · PubMed Central
Figure 2 PRISMA diagram of selection criteria for biomarkers explored in this review.
Figure 2 PRISMA diagram of selection criteria for biomarkers explored in this review.CC BY · PubMed Central
Figure 3 Summary of new candidate biomarkers, highlighted in this review. Although substantially variable in size, from the < 1kDa TF Antigen to the >1 MDa MUC1 glycoprotein, these surface biomarkers offer a potential to reveal early CRC lesion development, particularly when used as a library of markers that could identify lesions with heterogeneous subpopulations.
Figure 3 Summary of new candidate biomarkers, highlighted in this review. Although substantially variable in size, from the < 1kDa TF Antigen to the >1 MDa MUC1 glycoprotein, these surface biomarkers offer a potential to reveal early CRC lesion development, particularly when used as a library of markers that could identify lesions with heterogeneous subpopulations.CC BY · PubMed Central
Figure 4 Proposed workflow for future concepts in particle-based targeted imaging. (A) Surface functionalization scheme, using a library of antibodies against selected surface biomarker targets. Antibodies are covalently coupled to a PEG-functionalized particle, with either a fluorescent barcode, or hyperpolarization (used in (D) below). Particle libraries may have multiple targeting antibodies on a single particle (box, left) or single-target particles, mixed to illuminate multiple biomarkers on a heterogeneous lesion (box, right). (B) Illustrated identification of lesions, via a library of particles. (C) Imaging workflow for fluorescence-based or Raman-based image capture. (D) Hyperpolarized Si particles preserve signal over a sufficient lifetime to enable magnetic resonance-based imaging. The MRI image of the abdomen adopted from the depiction of volvulus on Wikipedia under the Creative Commons license: https://en.wikipedia.org/wiki/Volvulus).
Figure 4 Proposed workflow for future concepts in particle-based targeted imaging. (A) Surface functionalization scheme, using a library of antibodies against selected surface biomarker targets. Antibodies are covalently coupled to a PEG-functionalized particle, with either a fluorescent barcode, or hyperpolarization (used in (D) below). Particle libraries may have multiple targeting antibodies on a single particle (box, left) or single-target particles, mixed to illuminate multiple biomarkers on a heterogeneous lesion (box, right). (B) Illustrated identification of lesions, via a library of particles. (C) Imaging workflow for fluorescence-based or Raman-based image capture. (D) Hyperpolarized Si particles preserve signal over a sufficient lifetime to enable magnetic resonance-based imaging. The MRI image of the abdomen adopted from the depiction of volvulus on Wikipedia under the Creative Commons license: https://en.wikipedia.org/wiki/Volvulus).CC BY · PubMed Central

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Cited by

Sorted by citations

Metadata

Authors
Ramezani, S., Parkhideh, A., Bhattacharya, P. K., Farach-Carson, M. C., & Harrington, D. A.
Venue
Frontiers in Oncology
Publisher
Frontiers Media SA
Published
2021-07-05
Volume
11
ISSN
2234-943X
DOI
10.3389/fonc.2021.657701
PMC
PMC8287259
Cited by
11
References
2
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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