Open Access

Differential extracellular matrix proteomic signatures in colorectal tumors from Appalachian and non‑Appalachian patients

  • Authors:
    • Alexander T. Sougiannis
    • Harrison B. Taylor
    • Stephen C. Zambrzycki
    • Lindsey Conroy
    • Rachel Strubler
    • Christin Edge
    • Richard R. Drake
    • Kristin Wallace
    • Derek Allison
    • Eun Lee
    • Ramon C. Sun
    • Peggi M. Angel
  • View Affiliations

  • Published online on: June 26, 2025     https://doi.org/10.3892/ol.2025.15159
  • Article Number: 413
  • Copyright: © Sougiannis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging evidence reports that regulation of the extracellular matrix influences the progression of colorectal cancer (CRC). The present study investigated regulation of the extracellular matrix proteome in colorectal malignancy within a high‑risk Appalachian population compared with non‑Appalachian populations. A targeted mass spectrometry imaging proteomic method directed at collagen regulation was used. Tissue microarrays (TMAs) comprising of matched CRC with adjacent normal to tumor (NAT) from 45 patients were constructed into 86 samples to evaluate the extracellular matrix proteome (ECM). A total of five specific peaks were discovered to differ between NAT and tumor with high sensitivity and specificity by receiver operating characteristic (AUROC) ≥0.7, Wilson/Brown P<0.0002. Evaluation of patient TMA cores showed increased levels of combined ECM peptides in advanced stage Appalachian CRC (III + IV) compared with early staged CRC (I + II) (AUROC 0.8595; 95% confidence interval, 0.8190‑0.8999; Wilson/Brown P<1.0x10‑15), contrasting with the non‑Appalachian tumors, which showed a decreased ability to discriminate between early and late stage (AUROC 0.6618; 95% confidence interval, 0.6126‑0.7110; Wilson/Brown P<1.0x10‑9). Comparison of advanced stage CRCs between Appalachian and non‑Appalachian populations showed high sensitivity and specificity in distinguishing the populations (AUROC 0.7612; 95% confidence interval, 0.7109‑0.8114; Wilson/Brown P<3.0x10‑15). History of smoking, sex and tumor origin location did not show significant ability to distinguish by AUROC. A combination of high mass resolution, high mass accuracy spatial proteomics and sequencing proteomics by liquid chromatography coupled to tandem mass spectrometry revealed that fibrillar collagens were spatially regulated within the CRC tumor microenvironment. Fibrillar collagen post‑translational modifications of hydroxylated proline revealed distinct spatial separation based on the presence of a number of hydroxylated proline sites. The present study highlighted that the targeted mass spectrometry imaging of the ECM proteome may provide new insight and novel predictive tools for understanding CRC, particularly among Appalachian patients.
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September-2025
Volume 30 Issue 3

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Spandidos Publications style
Sougiannis AT, Taylor HB, Zambrzycki SC, Conroy L, Strubler R, Edge C, Drake RR, Wallace K, Allison D, Lee E, Lee E, et al: Differential extracellular matrix proteomic signatures in colorectal tumors from Appalachian and non‑Appalachian patients. Oncol Lett 30: 413, 2025.
APA
Sougiannis, A.T., Taylor, H.B., Zambrzycki, S.C., Conroy, L., Strubler, R., Edge, C. ... Angel, P.M. (2025). Differential extracellular matrix proteomic signatures in colorectal tumors from Appalachian and non‑Appalachian patients. Oncology Letters, 30, 413. https://doi.org/10.3892/ol.2025.15159
MLA
Sougiannis, A. T., Taylor, H. B., Zambrzycki, S. C., Conroy, L., Strubler, R., Edge, C., Drake, R. R., Wallace, K., Allison, D., Lee, E., Sun, R. C., Angel, P. M."Differential extracellular matrix proteomic signatures in colorectal tumors from Appalachian and non‑Appalachian patients". Oncology Letters 30.3 (2025): 413.
Chicago
Sougiannis, A. T., Taylor, H. B., Zambrzycki, S. C., Conroy, L., Strubler, R., Edge, C., Drake, R. R., Wallace, K., Allison, D., Lee, E., Sun, R. C., Angel, P. M."Differential extracellular matrix proteomic signatures in colorectal tumors from Appalachian and non‑Appalachian patients". Oncology Letters 30, no. 3 (2025): 413. https://doi.org/10.3892/ol.2025.15159