Prognostic significance of IMMT expression in surgically-resected lung adenocarcinoma

Thorac Cancer. 2019 Nov;10(11):2142-2151. doi: 10.1111/1759-7714.13200. Epub 2019 Oct 3.

Abstract

Background: Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis.

Methods: IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival.

Results: High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation.

Conclusion: Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.

Keywords: IMMT; TCGA database; immunohistochemistry; lung adenocarcinoma; prognostic marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / surgery*
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery*
  • Male
  • Mitochondrial Proteins / metabolism*
  • Muscle Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • IMMT protein, human
  • Mitochondrial Proteins
  • Muscle Proteins