PLoS ONE (Jan 2013)

Aberrant expression of Beclin-1 and LC3 correlates with poor prognosis of human hypopharyngeal squamous cell carcinoma.

  • Juan Wang,
  • Xin-Liang Pan,
  • Li-Jie Ding,
  • Da-Yu Liu,
  • Da-Peng Lei,
  • Tong Jin

DOI
https://doi.org/10.1371/journal.pone.0069038
Journal volume & issue
Vol. 8, no. 7
p. e69038

Abstract

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Beclin-1, a key regulator of autophagy. Microtubule-associated protein 1 light chain 3 (LC3), is involved in autophagsome formation during autophagy. The autophagic genes beclin-1 and LC3 paly an important role in the development and progression of tumor. This study was designed to investigate the expression of beclin-1 and LC3 and to clarify their clinical significance in hypopharyngeal squamous cell carcinoma (HSCC).Eighty-two surgical hypopharyngeal squamous cell carcinoma specimens and fifty-four adjacent non-cancerous mucosal epithelial tissues were obtained. Beclin-1 and LC3-II expression was examined by immunohistochemistry, real-time RT-PCR and Western blotting assays. Correlations with patient clinical characteristics and overall survival were evaluated.Beclin-1 was positively expressed in 42.7% (35/82) of HSCC specimens (adjacent non-cancerous tissues, 79.6%, 43/54; P<0.0001). Furthermore, 41.5% (34/82) of HSCC specimens exhibited high LC3 immunoreactivity (adjacent non-cancerous tissues, 74.1%, 40/54; P=0.0002). Beclin-1 and LC3-II mRNA transcript levels were significantly lower in HSCCs than in paired non-cancerous tissues (P<0.0001, P=0.0001, respectively). Similarly, western blotting assays showed that beclin-1 and LC3-II were markedly decreased in HSCCs (P=0.02, P=0.004, respectively). A positive correlation was observed between the mRNA transcript levels of beclin-1 and LC3-II in HSCCs (r=0.51, P<0.0001; 95%CI: 0.273 to 0.689). Beclin-1 and LC3 expression were significantly correlated with T categories, differentiation and lymph node metastasis. Negative beclin-1 immunoreactivity and low LC3 expression were associated with poorer overall survival in HSCC patients (P<0.0001, P=0.0145, respectively). Multivariate analysis revealed that beclin-1 was an independent prognositic factor for overall survival.Beclin-1 and LC3-II are downregulated in HSCCs and their aberrant expression correlates with poor prognosis of HSCCs.