Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2021; 27(39): 6673-6688
Published online Oct 21, 2021. doi: 10.3748/wjg.v27.i39.6673
Diagnostic usefulness of selected proteases and acute phase factors in patients with colorectal adenocarcinoma
Tadeusz Sebzda, Jan Gnus, Barbara Dziadkowiec, Miroslaw Latka, Jakub Gburek
Tadeusz Sebzda, Barbara Dziadkowiec, Department of Pathophysiology, Wroclaw Medical University, Wroclaw 50-368, Poland
Jan Gnus, Department of Physiotherapy, Wroclaw Medical University, Wroclaw 50-355, Poland
Miroslaw Latka, Department of Biomedical Engineering, Wroclaw University of Science and Technology, Wroclaw 50-370, Poland
Jakub Gburek, Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Wroclaw 50-556, Poland
Author contributions: Sebzda T, Gnus J and Gburek J performed the clinical studies; Sebzda T and Gburek J wrote the initial manuscript; All authors contributed to data analysis and the manuscript revisions.
Institutional review board statement: The study protocol was approved by the Ethics Committee of Wroclaw Medical University (KB 185/2013).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Barbara Dziadkowiec, MD, Doctor, Department of Pathophysiology, Wroclaw Medical University, Marcinkowskiego 1, Wroclaw 50-368, Poland. dziadkowiecbarbara@gmail.com
Received: April 7, 2021
Peer-review started: April 7, 2021
First decision: May 27, 2021
Revised: July 7, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 21, 2021
Processing time: 195 Days and 15.7 Hours
Abstract
BACKGROUND

Uncontrolled growth and loss of control over basic metabolic functions, leading to invasive proliferation and metastases, are the salient traits of malignant tumors in general and colorectal cancer in particular. Invasion and metastases hinder effective tumor treatment. While surgical techniques and radiotherapy can be used to remove tumor focus, only chemotherapy can eliminate dispersed neoplastic cells. However, the efficacy of the latter method is limited in the advanced stages of the disease. Therefore, recognition of the mechanisms involved in neoplastic cell spreading is indispensable for developing effective therapies.

AIM

To use a number of biomarkers involved in cancer progression and identify a panel that could be used for effective early diagnosis.

METHODS

We recruited 185 patients with colorectal adenocarcinoma (98 men, 87 women with median age 63). Thirty-five healthy controls were sex and age-matched. Dukes’ staging was as follows: A = 22, B = 52, C = 72, D = 39. We analyzed patients' blood serum before surgery. We determined: (1) Cathepsin B (CB) with Barrett's method (fluorogenic substrate); (2) Leukocytic elastase (LE) in a complex with alpha 1 trypsin inhibitor (AAT) using the immunoenzymatic MERCK test; (3) Total sialic acid (TSA) with the colorimetric periodate-resorcinol method; (4) Lipid-bound sialic acid (LASA) with the colorimetric Taut's method; and (5) The antitrypsin activity (ATA) employing the colorimetric test.

RESULTS

In patients, the values of the five biochemical parameters were as follows: CB = 16.1 ± 8.8 mU/L, LE = 875 ± 598 µg/L, TSA = 99 ± 31 mg%, LASA = 0.68 ± 0.33 mg%, and ATA = 3211 ± 1504 U/mL. Except for LASA, they were significantly greater than those of controls: CB = 11.4 ± 6.5 mU/L, LE = 379 ± 187 µg/L, TSA = 71.4 ± 15.1 mg%, LASA = 0.69 ± 0.28 mg%, and ATA = 2016 ± 690 U/mL. For CB and LASA, the differences between the four Dukes’ stages and controls were not statistically significant. The inter-stage differences for CB and LASA were also absent. The receiver operating characteristic (ROC) analysis revealed the potential diagnostic value of CB, TSA, and ATA. The area under ROC, sensitivity, and specificity for these three parameters were: 0.85, 72%, 90%; 0.75, 66%, 77%; and 0.77, 63%, 84%, respectively. The sensitivity and specificity for the three-parameter panel CB-TSA-ATA were equal to 88.2% and 100%, respectively.

CONCLUSION

The increased value of CB, TSA, and ATA parameters are associated with tumor biology, invasion, and metastasis of colorectal cancer. The presented evidence suggests the potential value of the CB-TSA-ATA biochemical marker panel in early diagnostics.

Keywords: Colorectal cancer; Cathepsin B; Acute phase reactants; Colorectal adenocarcinoma; Acute phase factor

Core Tip: We searched for biomarkers applicable to the early detection of colorectal adenocarcinoma. Five parameters were determined in sera of patients and healthy individuals: Cathepsin B activity, total sialic acids concentration, lipid-associated sialic acids concentration, elastase concentration, and alpha 1 antitrypsin activity. We performed receiver operating characteristic analysis for single and multiple parameters. While the sensitivity and specificity were not very high for single parameters, the combined analysis of cathepsin B, alpha 1 antitrypsin, and total sialic acids concentration yielded 88% sensitivity and 100% specificity. We believe that this set of markers can be useful in clinical practice.