Expression of ER stress and autophagy‐related molecules in human non‐small cell lung cancer and premalignant lesions

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P><P>Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation of unfolded or misfolded proteins in the ER (ER stress). Autophagy is a lysosomal pathway involved in the turnover of cellular macromolecules and organelles, which emerging data indicate that ER stress is also a potent inducer of autophagy. ER stress and autophagy are involved in human cancer. We examined the expression of ER stress‐related proteins [GRP78 and C/EBP homologous protein (CHOP)] and autophagic proteins (Beclin‐1 and LC3) in non‐small cell lung carcinomas (NSCLCs), bronchioloalveolar carcinomas (BACs) and atypical adenomatous hyperplasias (AAHs) to understand their role in the NSCLC pathogenesis. The expression of GRP78 and CHOP, Beclin‐1 and LC3 were analyzed using immunohistochemistry on tissue sections from 133 NSCLC (69 squamous cell carcinomas, 56 adenocarcinomas (AC) and eight other NSCLCs), 21 BAC and 9 AAH. Expression of GRP78 and Beclin‐1 was correlated with low tumor stage (<I>p</I> < 0.001 and <I>p</I> = 0.019, respectively) and longer survival (<I>p</I> = 0.007 and <I>p</I> <0.001, respectively) by Kaplan–Meier analysis. However, CHOP was correlated with high tumor stage (<I>p</I> = 0.038) and shorter survival (<I>p</I> = 0.012). Expression of GRP78 and Beclin‐1 was positively correlated (<I>p</I> = 0.006). Our study showed that the expression of GRP78, CHOP, Beclin‐1 and LC3 in lung cancer and its relation with clinicopathologic factors and patients survival. These results suggest that GRP78, CHOP and Beclin‐1 may play an important role in tumorigenesis of lung AC and may serve as new prognostic indicators for outcome of the patients with NSCLC.</P>