Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma

Ann Surg Oncol. 2024 Jul;31(7):4822-4829. doi: 10.1245/s10434-024-15116-z. Epub 2024 Mar 9.

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.

Keywords: GPX2; Glutathione peroxidase 2; Lung adenocarcinoma; N nuclear factor erythroid 2-related factor 2 (Nrf2); Reactive oxygen species.

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / surgery
  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / surgery
  • Adult
  • Aged
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Female
  • Follow-Up Studies
  • Glutathione Peroxidase* / metabolism
  • Humans
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • Glutathione Peroxidase
  • GPX2 protein, human
  • Biomarkers, Tumor
  • RNA, Messenger