Glutaredoxin 2 Protein (Grx2) - as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients

Sep 21, 2026

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Glutaredoxin 2 (Grx2; Glrx2) is a mitochondrial glutathione-dependent oxidoreductase that regulates glutathione homeostasis and mitochondrial redox balance, influencing oxidative stress–driven processes relevant to cancer. Immunohistochemical evaluation in colon adenocarcinoma samples assessed primary tumors (stage I–II) and regional lymph node metastasis (stage III) alongside multiple clinicopathological variables and PCNA expression. Grx2 high expression correlated with tumor grade, invasion depth, lymph node involvement, angioinvasion, and overall staging, with stage-dependent frequencies (87% stage I vs 33% stage II vs 1% stage III) and survival associations. Multivariate analysis identified Grx2 expression as an independent prognostic factor, supported by serum findings and in vitro validation using colorectal cancer cell lines with qRT-PCR and Western blot.

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Article Glutaredoxin 2 Protein (Grx2) as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients Marlena Brzozowa-Zasada 1, *, Adam Piecuch 1, Karolina Bajdak-Rusinek 2, Karolina Goła˛bek 3, Marek Michalski 1,4, Kamil Janelt 2 and Natalia Matysiak 1 Citation: Brzozowa-Zasada, M.; Piecuch, A.; Bajdak-Rusinek, K.; Goła˛bek, K.; Michalski, M.; Janelt, K.; Matysiak, N. Glutaredoxin 2 Protein (Grx2) as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients. Int. J. Mol. Sci. 2024, 25, 1060. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25021060](doi.org/10.3390/ijms25021060) Academic Editor: Consolato M. Sergi Received: 28 November 2023 Revised: 3 January 2024 Accepted: 9 January 2024 Published: 15 January 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; [nmatysiak@sum.edu.pl](nmatysiak@sum.edu.pl) (N.M.) 2 Department of Medical Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland 3 Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Jordana 19, 41-808 Zabrze, Poland 4 Zabrze Silesian Nanomicroscopy Centre in Zabrze, Silesia LabMed-Research and Implementation Centre, Medical University of Silesia, 40-055 Katowice, Poland * [Correspondence: mbrzozowa@sum.edu.pl or marlena.brzozowa@op.pl](Correspondence: mbrzozowa@sum.edu.pl or marlena.brzozowa@op.pl) Abstract: Glutaredoxin 2 (Grx2; Glrx2) is a glutathione-dependent oxidoreductase located in mitochondria, which is central to the regulation of glutathione homeostasis and mitochondrial redox, and plays a crucial role in highly metabolic tissues. In response to mitochondrial redox signals and oxidative stress, Grx2 can catalyze the oxidation and S-glutathionylation of membrane-bound thiol proteins in mitochondria. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of Grx2 protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III) . The results of our study revealed a significant relationship between the immunohistochemical expression of Grx2 and tumor histological grade, depth of invasion, regional lymph node involvement, angioinvasion, staging, and PCNA immunohistochemical expression. It was found that 87% of patients with stage I had high levels of Grx2 expression. In contrast, only 33% of patients with stage II and 1% of patients with stage III had high levels of Grx2 expression. Moreover, the multivariate analysis revealed that the immunohistochemical expression of Grx2 protein apart from the grade of tumor differentiation was an independent prognostic factors for the survival of patients with colon adenocarcinoma. Studies analyzing Grx2 levels in patients’ blood confirmed that the highest levels of serum Grx2 protein was also found in stage I patients, which was reflected in the survival curves. A higher level of Grx2 in theserum has been associated with a more favorable outcome. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western Blot. Keywords: glutaredoxins; redox balance; colon adenocarcinoma; glutathione (GSH); prognostic factor; oxidative

FAQs

What role does Grx2 play in mitochondria and cancer biology?

Grx2 is a mitochondrial glutathione-dependent oxidoreductase involved in regulating glutathione homeostasis and mitochondrial redox. It can affect cancer development through catalyzing oxidation and S-glutathionylation of mitochondrial thiol proteins under oxidative stress.

How was Grx2 expression evaluated in colon adenocarcinoma patients?

Grx2 protein expression was assessed using immunohistochemical analysis on colon adenocarcinoma samples from patients with primary tumors (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The study also examined serum Grx2 levels and supported findings with cell line experiments using qRT-PCR and Western blot.

Does Grx2 expression independently predict patient survival?

Yes. Multivariate analysis indicated that immunohistochemical Grx2 expression, beyond tumor differentiation grade, acted as an independent prognostic factor for survival in colon adenocarcinoma patients. Higher serum Grx2 levels were also associated with a more favorable outcome.

Sep 21, 2026

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