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Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma

  • Translational Research
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified.

Methods

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance.

Results

qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS.

Conclusions

GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

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Acknowledgment

We thank Joe Barber, Jr., PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Asato Hashinokuchi MD, Saito Shunichi MD, Kyoto Matsudo MD, Taichi Nagano MD, Fumihiko Kinoshita MD, PhD, Takaki Akamine MD, PhD, Mikihiro Kohno MD, PhD, Tomoyoshi Takenaka MD, PhD & Tomoharu Yoshizumi MD, PhD

  2. Department of Thoracic Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Fukuoka, Japan

    Taichi Matsubara MD, PhD

  3. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita, Japan

    Yuya Ono MD

  4. Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yoshinao Oda MD, PhD

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  1. Asato Hashinokuchi MD
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Corresponding author

Correspondence to Taichi Matsubara MD, PhD.

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All authors declare no conflicts of interest associated with this research. The graphical abstract has been designed using freely available resources from Flaticon.com.

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Supplementary Information

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10434_2024_15116_MOESM1_ESM.pdf

Nrf2 expression in lung adenocarcinoma specimens. Examples of Nrf2 staining with intensity scores of (a) 0, (b) 1, and (c) 2. Scale bar: 200 μm. Nrf2, nuclear factor erythroid 2-related factor 2; IS, intensity score (PDF 78 kb)

10434_2024_15116_MOESM2_ESM.pdf

The correlation between GPX2 and NFE2L2 expression in lung adenocarcinoma as determined by GSEA using a dataset from TCGA (a). Nrf2 expression in patients with surgically resected lung adenocarcinoma and high (n = 30) or low GPX2 (n = 30) expression on IHC analysis (b). GPX2, glutathione peroxidase 2; GSEA, gene set enrichment analysis; IHC, immunohistochemistry; Nrf2, nuclear factor erythroid 2-related factor 2; TCGA, The Cancer Genome Atlas (PDF 77 kb)

10434_2024_15116_MOESM3_ESM.pdf

GPX2 expression in normal lung tissue and lung adenocarcinoma tissue in TCGA analysis (a). Kaplan–Meier curves of overall survival in patients with surgically resected lung adenocarcinoma according to GPX2 expression in TCGA analysis (b). GPX2, glutathione peroxidase 2; TCGA, The Cancer Genome Atlas (PDF 53 kb)

Supplementary file4 (DOCX 14 kb)

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Hashinokuchi, A., Matsubara, T., Ono, Y. et al. Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma. Ann Surg Oncol (2024). https://doi.org/10.1245/s10434-024-15116-z

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  • DOI: https://doi.org/10.1245/s10434-024-15116-z

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