ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1628069
This article is part of the Research TopicExploring Molecular Mechanisms in Cancer through Tumor Molecular PathologyView all 8 articles
Combined Serine Protease PRSS22 and CEA mRNA Analysis Identifies the Majority of Colon Cancer Patients that Recur within 12 years
Provisionally accepted
Alaa Mohamed Farag1
Manar AbdelMageed1Lina Olsson1Faten Zahran2Nabila Zein3Gudrun Lindmark4Marie-Louise Hammarström1Sten Hammarström1,4
Basel Sitohy1*- 1Umeå University, Umeå, Sweden
- 2Departemnt of Biochemisrty, zagazig, Zagazig, Egypt
- 3zagazig university, Zagazig, Egypt
- 4Lund university, Lund, Sweden
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Introduction: Proteases play an important role in tumor progression. The predictive efficacy of proteases PRSS3 and PRSS22 mRNA levels for predicting relapse in surgically treated colon cancer (CC) patients was assessed. Methods: mRNA expression was quantified in 371 half lymph nodes (LNs) from 121 CC patients, 77 control LNs (13 patients), 66 primary colon tumors, and 30 normal colon tissues of these patients. Patients were also stratified according to their CEA mRNA level. The occurrence of relapse following curative surgery was evaluated using the Cox regression and Kaplan-Meier survival model analyses. Protein expression was examined through immunohistochemistry. Results: PRSS22 was superior to PRSS3 in identifying patients at risk of recurrence. Thus, high PRSS22 levels in LNs identified 76.5% of those who recurred, while PRSS3 only identified 17.6% of these patients and these were in TNM stages III and IV. The Kaplan-Meier analysis indicated that CC patients exhibiting elevated PRSS22 levels in lymph nodes experienced a reduction in survival time, averaging 37 months over the follow-up period (p = 0.009) and a 3-fold increased hazard risk (1.3–6.0; p = 0.01). In the group with low PRSS22 levels, only one patient experienced relapse at the 12-year follow-up when CEA mRNA analysis was included. A fraction of CEA-positive tumor cells expressed PRSS22 protein. Conclusion: The importance of the secreted serine protease, S1 family member PRSS22 in tumor progression is highlighted. It shows promise as a biomarker for CC prognosis and as a target to prevent tumor spread by inhibiting its enzymatic activity.
Keywords: Colon Cancer, Serine Proteases, PRSS3, PRSS22, CEA, Regional lymph nodes, prognosis, Mrna analysis
Received: 27 May 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Farag, AbdelMageed, Olsson, Zahran, Zein, Lindmark, Hammarström, Hammarström and Sitohy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Basel Sitohy, Umeå University, Umeå, Sweden
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