Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in patients receiving docetaxel-platinum induction chemotherapy

Korean J Intern Med. 2019 Mar;34(2):401-408. doi: 10.3904/kjim.2017.015. Epub 2018 Sep 6.

Abstract

Background/aims: The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety.

Methods: This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78.

Results: Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors.

Conclusion: Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.

Keywords: BECN1 protein, human; Carcinoma, non-small-cell lung; Induction chemotherapy.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Beclin-1 / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • DNA-Binding Proteins / metabolism*
  • Docetaxel / therapeutic use
  • Endonucleases / metabolism*
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Induction Chemotherapy
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Platinum Compounds / therapeutic use
  • Republic of Korea / epidemiology
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • BECN1 protein, human
  • Beclin-1
  • DNA-Binding Proteins
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Platinum Compounds
  • Docetaxel
  • ERCC1 protein, human
  • Endonucleases