Relationship between MTA1 and spread through air space and their joint influence on prognosis of patients with stage I-III lung adenocarcinoma

Lung Cancer. 2018 Oct:124:211-218. doi: 10.1016/j.lungcan.2018.07.040. Epub 2018 Jul 29.

Abstract

Objective: To characterize the relationship between metastasis-associated protein 1 (MTA1) and spread through air spaces (STAS), and to investigate the joint prognostic value of MTA1 and STAS in resected lung adenocarcinomas.

Methods: We retrospectively reviewed 208 operated patients with stage I-III lung adenocarcinoma from January 2009 to December 2014. STAS was identified by H&E staining. Expression level of MTA1 was determined by immunohistochemistry. The relationship between MTA1 and STAS was determined by using a logistic regression model. The synergistic effects of MTA1 and STAS on prognosis were analyzed using a Cox proportional hazards regression model.

Results: Patients with either STAS or high expression of MTA1 had significantly worse overall survival (OS) and shorter recurrence-free survival (RFS) than those without STAS or with low expression of MTA1 (p < 0.001). Among 107 patients with STAS presence in lung adenocarcinomas, 57 (53.3%) cases had high expression of MTA1. High expression of MTA1 was positively associated with the increased frequency of STAS presence (p < 0.01). Subgroup analysis showed that the patients with both high expression of MTA1 and STAS-positive presence had significantly worst OS and shortest RFS compared with the others (p < 0.001), while the patients with high expression of MTA1 /STAS-negative presence shared similar RFS with those with high expression of MTA1 /STAS-positive presence. Furthermore, high MTA1 levels in STAS-positive patients was associated with a higher risk of postoperative metastasis and recurrence (p < 0.001).

Conclusions: STAS was more frequently observed in adenocarcinomas with high MTA1 expression levels. MTA1 was associated with a higher risk of worse overall survival among patients with STAS and could provide helpful prognostic information in STAS-positive patients with stage I-III lung adenocarcinoma.

Keywords: Lung adenocarcinoma; MTA1; Prognosis; STAS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Retrospective Studies
  • Survival Analysis
  • Trans-Activators

Substances

  • MTA1 protein, human
  • Repressor Proteins
  • Trans-Activators
  • Histone Deacetylases