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Thioredoxin reductase as a novel biomarker for the diagnosis and efficacy prediction of gastrointestinal malignancy: a large-scale, retrospective study

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Abstract

Background

Our aim was to investigate the rationality and accuracy of plasma TrxR activity as an efficient tool in the early diagnosis of gastrointestinal malignancy, and whether TrxR can be used to evaluate the therapeutic efficacy of gastrointestinal malignancy.

Methods

We enrolled a total of 5091 cases, including 3736 cases in gastrointestinal malignancy, 964 in benign diseases, and 391 cases in healthy controls. We also performed receiver operating characteristic (ROC) analysis to evaluate diagnostic efficiency of TrxR. Finally, we detected pre- and post-treatment level of TrxR and common tumor markers.

Results

The plasma TrxR level in patients with gastrointestinal malignancy [8.4 (6.9, 9.7) U/mL] was higher than that in patients with benign disease [5.8 (4.6, 6.9) U/mL] and healthy control [3.5 (1.4, 5.4) U/mL]. Plasma TrxR showed a significant diagnostic advantage with an AUC of 0.897, compared with conventional tumor markers. In addition, the combination of TrxR and conventional tumor markers can further improve the diagnostic efficiency. We derived the optimal cut-off value of plasma TrxR as a diagnostic marker of gastrointestinal malignancy according to Youden index of 6.15 U/mL. After measuring the change trend of TrxR activity and conventional tumor markers before and after anti-tumor treatments, we found that their change trend was generally consistent, and the plasma TrxR activity was significantly decreased in patients treated with chemotherapy, targeted therapy and immunotherapy.

Conclusions

Our findings recommend that plasma TrxR activity could be monitored as an efficient tool for the early diagnosis of gastrointestinal malignancy and as a feasible tool to evaluate the therapeutic effect.

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Availability of data and materials

The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

Not applicable.

Funding

This work was supported by National Natural Science Foundation of China (No. 81802667), Natural Science Foundation of Jiangsu Province (BK20180133) and Nanjing Outstanding Youth Fund (No. JQX20009).

Author information

Author notes

  1. Yixuan Hu, Yinxing Zhu and Weiwei Nie authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China

    Yixuan Hu, Yinxing Zhu, Junfeng Shi, Xiaowei Wei, Cuiju Tang & Wenwen Zhang

  2. Department of Radiation Oncology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an, 223300, China

    Yinxing Zhu

  3. Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China

    Weiwei Nie

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  1. Yixuan Hu
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Contributions

WZ, CT and YH conceived the study and reviewed the manuscript. WZ, WN performed bioinformatics analysis. YH, YZ, JS, and XW collected clinical information. YZ and YH performed statistical analysis. YH and WN wrote the manuscript. All authors contributed to the conception of the study and the preparation and approval of the paper.

Corresponding authors

Correspondence to Cuiju Tang or Wenwen Zhang.

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The authors declare no competing interests.

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This study is approved by the Ethics Committee of Nanjing First Hospital. Informed consent was obtained from all patients.

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Hu, Y., Zhu, Y., Nie, W. et al. Thioredoxin reductase as a novel biomarker for the diagnosis and efficacy prediction of gastrointestinal malignancy: a large-scale, retrospective study. Int J Clin Oncol 28, 880–892 (2023). https://doi.org/10.1007/s10147-023-02350-w

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