title: Expression of ER stress and autophagy-related molecules in human non-small cell lung cancer and premalignant lesions.
abstract: 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 (p < 0.001 and p = 0.019, respectively) and longer survival (p = 0.007 and p <0.001, respectively) by Kaplan-Meier analysis. However, CHOP was correlated with high tumor stage (p = 0.038) and shorter survival (p = 0.012). Expression of GRP78 and Beclin-1 was positively correlated (p = 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.
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Tack Keun
authors.initials: TK
authors.lastname: Yu
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Chu
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.forename: Myoung Jae
authors.initials: MJ
authors.lastname: Kang
authors.forename: Dong Geun
authors.initials: DG
authors.lastname: Lee
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Kim
authors.forename: Ju Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Myoung Ja
authors.initials: MJ
authors.lastname: Chung
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D051742:Transcription Factor CHOP