Frontiers in Oncology (May 2022)

Prognostic Value and Potential Mechanism of MTFR2 in Lung Adenocarcinoma

  • Zengzhi Lian,
  • Pei Pang,
  • Yan Zhu,
  • Wenwen Du,
  • Jintao Zhou

DOI
https://doi.org/10.3389/fonc.2022.832517
Journal volume & issue
Vol. 12

Abstract

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Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR1 family, which plays a crucial role in regulating oxidative phosphorylation. Recent studies indicate that it also participates in cancer carcinogenesis and development; however, the clinical significance of MTFR2 in lung adenocarcinoma has not been fully confirmed. Our current study investigated the relationships between clinical characteristics and MTFR2 expression based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GSE31210) dataset, and clinical histopathological sample cohort. In addition, Kaplan–Meier and Cox regression analyses were additionally performed to evaluate the association between MTFR2 expression and patient survival. Gene set enrichment analysis (GESA) was conducted to spot possible pathways associated with MTFR2. Moreover, a single-sample GESA (ssGESA) was performed to evaluate the association between MTFR2 expression and immune cell infiltration. Cell colony formation assay, CCK-8 assay, cell cycle assay, and transwell assay were performed to verify the cell proliferation, migration, and invasion abilities after interfering with MTFR2 in lung cancer cells. Western blot assay was applied to identify the underlying protein levels. The results indicated that the elevated MTFR2 expression in lung adenocarcinoma samples correlated with T stage (P < 0.001), N stage (P = 0.005), M stage (P = 0.015), pathological stage (P = 0.002), and TP53 status (P < 0.001). Patients with a higher MTFR2 expression correlated with poorer overall survival (P < 0.01) and progression-free survival (P = 0.002). Knockdown of MTFR2 inhibited cell proliferation, migration, and invasion via AKT-cyclin D1 signaling and EMT pathways. Moreover, MTFR2 expression significantly positively correlated with Th2 cells (P < 0.001). Taken together, MTFR2 could serve as a novel prognostic indicator and therapeutic target for lung adenocarcinoma.

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