Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 24;12(10):227.
doi: 10.3390/diseases12100227.

Thioredoxin System Protein Expression in Carcinomas of the Pancreas, Distal Bile Duct, and Ampulla in the United Kingdom

Khaled S Al-Hadyan  1   2 , Sarah J Storr  1 , Abed M Zaitoun  3   4 , Dileep N Lobo  5 , Stewart G Martin  1
Affiliations

Thioredoxin System Protein Expression in Carcinomas of the Pancreas, Distal Bile Duct, and Ampulla in the United Kingdom

Khaled S Al-Hadyan et al. Diseases. .

Abstract

Background: Poor survival outcomes in periampullary cancer highlight the need for improvement in biomarkers and the development of novel therapies. Redox proteins, including the thioredoxin system, play vital roles in cellular antioxidant systems. Methods: In this retrospective study, thioredoxin (Trx), thioredoxin-interacting protein (TxNIP), and thioredoxin reductase (TrxR) protein expression was assessed in 85 patients with pancreatic ductal adenocarcinoma (PDAC) and 145 patients with distal bile duct or ampullary carcinoma using conventional immunohistochemistry. Results: In patients with PDAC, high cytoplasmic TrxR expression was significantly associated with lymph node metastasis (p = 0.033). High cytoplasmic and nuclear Trx expression was significantly associated with better overall survival (p = 0.018 and p = 0.006, respectively), and nuclear Trx expression remained significant in multivariate Cox regression analysis (p < 0.0001). In distal bile duct and ampullary carcinomas, high nuclear TrxR expression was associated with vascular (p = 0.001) and perineural (p = 0.021) invasion, and low cytoplasmic TxNIP expression was associated with perineural invasion (p = 0.025). High cytoplasmic TxNIP expression was significantly associated with better overall survival (p = 0.0002), which remained significant in multivariate Cox regression analysis (p = 0.013). Conclusions: These findings demonstrate the prognostic importance of Trx system protein expression in periampullary cancers.

Keywords: ampullary cancer; bile duct cancer; pancreatic ductal adenocarcinoma; periampullary cancer; redox protein; thioredoxin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of this study; the collection, analyses, or interpretation of data; the writing of this manuscript; or the decision to publish the results.

Figures

Figure 1
Figure 1
Representative staining patterns of Trx system protein expression in patients with pancreatic ductal adenocarcinoma. (a) Benign pancreatic tissue, (b) weak staining of Trx, (c) moderate staining of Trx, (d) strong staining of Trx, (e) weak cytoplasmic staining and moderate nuclear staining of Trx, (f) weak cytoplasmic staining of TxNIP, (g) strong cytoplasmic staining of TxNIP, (h) weak staining of TrxR, and (i) moderate staining of TrxR. Photomicrographs are at 10× magnification, with 20× magnification inset box. Scale bar: 200 μm. Abbreviations: CS = cytoplasmic H-score, NS = nuclear H-score.
Figure 2
Figure 2
Kaplan–Meier analysis of overall survival showing the impact of cytoplasmic Trx (a), nuclear Trx (b), cytoplasmic TrxR (c), nuclear TrxR (d), and cytoplasmic TxNIP (e) expression in the pancreatic ductal adenocarcinoma cohort; significance was determined using the log-rank test.
Figure 3
Figure 3
Kaplan–Meier analysis of overall survival in the distal bile duct and ampullary carcinoma cohort. Panels a–e show the impact of cytoplasmic Trx (a), nuclear Trx (b), cytoplasmic TrxR (c), nuclear TrxR (d), and cytoplasmic TxNIP (e) expression in the distal bile duct and ampullary carcinoma cohort; significance was determined using the log-rank test. The numbers shown below the Kaplan–Meier survival curves are the number of patients at risk in a particular month. Panels f and g show the overall survival analysis between different subgroups of Trx expression based on expression profiles. Low nuclear/high cytoplasmic expression showed longer overall survival than the other three subgroups either against each separate subgroup (f) or when the three subgroups were combined (g).
Figure 3
Figure 3
Kaplan–Meier analysis of overall survival in the distal bile duct and ampullary carcinoma cohort. Panels a–e show the impact of cytoplasmic Trx (a), nuclear Trx (b), cytoplasmic TrxR (c), nuclear TrxR (d), and cytoplasmic TxNIP (e) expression in the distal bile duct and ampullary carcinoma cohort; significance was determined using the log-rank test. The numbers shown below the Kaplan–Meier survival curves are the number of patients at risk in a particular month. Panels f and g show the overall survival analysis between different subgroups of Trx expression based on expression profiles. Low nuclear/high cytoplasmic expression showed longer overall survival than the other three subgroups either against each separate subgroup (f) or when the three subgroups were combined (g).
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Cancer Research UK Pancreatic Cancer Statistics. [(accessed on 3 April 2024)]. Available online: https://www.cancerresearchuk.org/health-professional/cancer-statistics/s....
    1. Walter D., Schnitzbauer A.A., Schulze F., Trojan J. The diagnosis and treatment of ampullary carcinoma. Dtsch. Ärztebl. Int. 2023;120:729–735. doi: 10.3238/arztebl.m2023.0195. - DOI - PMC - PubMed
    1. Roos E., Strijker M., Franken L.C., Busch O.R., van Hooft J.E., Klümpen H.J., van Laarhoven H.W., Wilmink J.W., Verheij J., van Gulik T.M., et al. Comparison of short- and long-term outcomes between anatomical subtypes of resected biliary tract cancer in a Western high-volume center. HPB. 2020;22:405–414. doi: 10.1016/j.hpb.2019.07.011. - DOI - PubMed
    1. De Castro S.M., Van Heek N.T., Kuhlmann K.F., Busch O.R., Offerhaus G.J., van Gulik T.M., Obertop H., Gouma D.J. Surgical management of neoplasms of the ampulla of Vater: Local resection or pancreatoduodenectomy and prognostic factors for survival. Surgery. 2004;136:994–1002. doi: 10.1016/j.surg.2004.03.010. - DOI - PubMed

LinkOut - more resources