High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence.
OBJECTIVE
Recent reports have shown that endoplasmic reticulum stress is associated with cancer. However, the impacts of endoplasmic reticulum stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of endoplasmic reticulum stress-related genes (endoplasmic reticulum oxidoreductase 1L, protein kinase RNA-like endoplasmic reticulum kinase, activating transcription factor 6 and inositol-requiring kinase 1) and the outcome of lung adenocarcinoma.


METHODS
One hundred and twenty-six patients with surgically resected lung adenocarcinomas were subjected to an endoplasmic reticulum stress-related mRNA expression analysis using quantitative RT-PCR. The following parameters were analyzed for all the study patients: age, sex, disease stage, smoking status, lymph node invasion (ly), vascular invasion (v) and EGFR mutation status. We assigned patients to either a high-expression group or a low-expression group according to the expression levels of endoplasmic reticulum stress-related genes.


RESULTS
High expressions of endoplasmic reticulum stress-related genes were observed in patients with lower stages of lung adenocarcinoma and minimal vascular invasion. A Kaplan-Meier analysis showed significant differences in recurrence-free survival and overall survival between high-expression group and low-expression group. High inositol-requiring kinase 1 expression was an independent predictor of recurrence-free survival among patients with lung adenocarcinoma (hazard ratio, 0.396; 95% confidence interval, 0.188-0.834; P = 0.015).


CONCLUSIONS
Inositol-requiring kinase 1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients.
Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo.
Toshio
T
Sakatani
Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo.
Keita
K
Maemura
Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo.
Noriko
N
Hiyama
Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo.
Yosuke
Y
Amano
Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo.
Kousuke
K
Watanabe
Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo.
Hidenori
H
Kage
Department of Pathology, The University of Tokyo Hospital, Tokyo.
Masashi
M
Fukayama
Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo.
Jun
J
Nakajima
Department of Laboratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Yutaka
Y
Yatomi
Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo.
Takahide
T
Nagase
Department of Laboratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Daiya
D
Takai
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
endoplasmic reticulum stress; inositol-requiring enzyme 1 (IRE1); lung adenocarcinoma; non-small-cell lung cancer; prognosis