Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report.

Rapid tumor growth after cessation of molecularly targeted drugs, called "disease flare," may occur and affect the prognosis of lung cancer. However, this phenomenon has never been reported in ROS proto-oncogene 1 (ROS1) fusion-positive lung adenocarcinoma. Herein, we report a disease flare in a patient with ROS1 fusion-positive lung adenocarcinoma. A 60-year-old female was diagnosed with stage IVA ROS1 fusion-positive lung adenocarcinoma via bronchoscopy. Although crizotinib, an ROS1 tyrosine kinase inhibitor, achieved a partial response, a mass lesion appeared in the patient's right kidney 12 months after starting crizotinib, which was diagnosed pathologically as crizotinib-associated renal cysts (CARCs). Given that readministration of crizotinib repeatedly induced CARC-like aseptic inflammation that appeared to be disseminated around surgical site, crizotinib treatment had to be abandoned. Around 25 days after crizotinib cessation, she was referred to the emergency department with a convulsive seizure and hemiparesis due to new, rapidly growing brain metastases. Whole-brain irradiation and administration of another ROS1 tyrosine kinase inhibitor, entrectinib, markedly ameliorated the metastases and improved hemiparesis. This has been the first report of a disease flare after crizotinib cessation due to CARCs in a patient with ROS1 fusion-positive lung adenocarcinoma. Attention should be paid to disease flare, especially in the brain, when molecularly targeted medication is stopped due to adverse events in ROS1 fusion-positive lung adenocarcinoma. Switching to drugs that penetrate the blood-brain barrier could overcome disease flare in the brain.

Temporal variability of 137Cs concentrations in coastal sediments off Fukushima.

Large amounts of radiocesium were released into marine environments following the Fukushima Daiichi Nuclear Power Plant accident in March 2011. Released radiocesium influenced not only marine environment but also marine biota in Fukushima. Since marine biota as fisheries products is important for Japanese market, it is important to assess the distribution of radiocesium in coastal environment off Fukushima for safety concerns of radioactive contamination. Radiocesium concentrations in sediments are important for understanding fishing ground conditions and for proving the safety of fisheries products in Fukushima. In this study, monthly monitoring data collected from May 2011 to March 2020 were analyzed to describe the temporal variability of 137Cs concentrations in coastal sediments off Fukushima (total of 3647 samples from eight lines at depths of 7-125 m off Fukushima, and three sites in Matsukawa-ura Lagoon). The 137Cs concentration in sediment showed a decreasing trend, but our nonlinear model fitting suggested that this rate of decrease had slowed down. Additionally, 137Cs concentrations were up to 4.08 times greater in shallow sampling sites (7, 10, 20 m depth) following heavy rainfall events (before five months vs. after five months), such as typhoons. These observations were consistent with increasing input from particulate 137Cs fluxes from rivers and increasing dissolved 137Cs concentrations in seawater. Finally, our numerical modeling suggested that riverine 137Cs input could maintain 137Cs concentrations in coastal sediment. These results indicate that riverine 137Cs input following heavy rainfall events is the main factor for maintaining 137Cs concentrations in coastal sediments near the Fukushima Daiichi Nuclear Power Plant.

Factors controlling dissolved 137Cs activities in coastal waters on the eastern and western sides of Honshu, Japan.

The distributions of dissolved 137Cs in river, nearshore, and offshore waters on the east and west coasts of the Japanese island of Honshu were studied in 2018-2021, 7-10 years after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident. On the east side along the north western North Pacific (Fukushima Prefecture), estuarine processes, including desorption from riverine particles and dissolution into pore water from riverine particles that had settled to the seafloor, contributed to the maintenance of high dissolved 137Cs activities in nearshore and offshore waters. A survey and mass-balance calculation in a semi-enclosed estuarine area, the Matsukawa-ura, in the northern part of Fukushima, provided convincing evidence that rivers contributed to the influx of 137Cs to coastal waters. In contrast, the extremely low activities of dissolved and particulate 137Cs in the Tedori River of Ishikawa Prefecture on the western side of Japan along the Japan Sea suggested that inputs of riverine 137Cs made a negligible contribution to the increase of dissolved 137Cs activities in the nearshore and offshore waters. The relatively high dissolved 137Cs activities observed in the offshore waters of the Japan Sea were due to movement of FDNPP-derived 137Cs into the Japan Sea via the Tsushima Warm Current. Mechanisms controlling the distributions of 137Cs activities in coastal waters of the eastern and western sides of Japan therefore differ.

Multiple cerebral infarctions in ROS1-rearranged lung adenocarcinoma.

Rearrangements of specific tyrosine kinases are associated with an elevated risk of venous thrombosis in lung adenocarcinoma, although their effects on arterial thrombosis have not been fully elucidated. Here, we report two cases of ROS proto-oncogene 1 (ROS1)-rearranged lung adenocarcinoma with cerebral infarction during the peri-diagnostic period. Two cases took contrasting clinical courses: one patient could not receive targeted therapy because of a significant decline in performance status, whereas in the other patient, the performance status was maintained and targeted therapy drastically reduced the tumour size. Our cases suggest close monitoring could be considered in the selected cohort.

Standardized reporting systems of chest computed tomography in a population with low coronavirus disease 2019 prevalence: A retrospective comparative study.

PURPOSE: To compare the diagnostic performance and interobserver agreement of three reporting systems for computed tomography findings in coronavirus disease 2019 (COVID-19), namely the COVID-19 Reporting and Data System (CO-RADS), COVID-19 Imaging Reporting and Data System (COVID-RADS), and Radiological Society of North America (RSNA) expert consensus statement, in a low COVID-19 prevalence area. METHOD: This institutional review board approval single-institutional retrospective study included 154 hospitalized patients between April 1 and May 21, 2020; 26 (16.9 %; 63.2 ± 14.1 years, 21 men) and 128 (65.7 ± 16.4 years, 87 men) patients were diagnosed with and without COVID-19 according to reverse transcription-polymerase chain reaction results, respectively. Written informed consent was waived due to the retrospective nature of the study. Six radiologists independently classified chest computed tomography images according to each reporting system. The area under receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and interobserver agreements were calculated and compared across the systems using paired t-test and kappa analysis. RESULTS: Mean area under receiver operating characteristic curves were as follows: CO-RADS, 0.89 (95 % confidence interval [CI], 0.87-0.90); COVID-RADS, 0.78 (0.75-0.80); and RSNA expert consensus statement, 0.88 (0.86-0.90). Average kappa values across observers were 0.52 (95 % CI: 0.45-0.60), 0.51 (0.41-0.61), and 0.57 (0.49-0.64) for CO-RADS, COVID-RADS, and RSNA expert consensus statement, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were the highest at 0.71, 0.53, 0.72, 0.96, and 0.56 in the CO-RADS; 0.56, 0.31, 0.54, 0.95, and 0.35 in the COVID-RADS; 0.83, 0.49, 0.61, 0.96, and 0.55 in the RSNA expert consensus statement, respectively. CONCLUSIONS: The CO-RADS exhibited the highest specificity, positive predictive value, which are especially important in a low-prevalence population, while maintaining high accuracy and negative predictive value, demonstrating the best performance in a low-prevalence population.

Diagnostic prediction of COVID-19 based on clinical and radiological findings in a relatively low COVID-19 prevalence area.

BACKGROUND: Distinguishing coronavirus disease 2019 (COVID-19) pneumonia from other lung diseases is often difficult, especially in a highly comorbid patient population in a low prevalence region. We aimed to distinguish clinical data and computed tomography (CT) images between COVID-19 and other lung diseases in an advanced care hospital. METHODS: We assessed clinical characteristics, laboratory data, and chest CT images of patients with COVID-19 and non-COVID-19 patients who were suspected of having COVID-19 between February 20 and May 21, 2020, at the University of Tokyo Hospital. RESULTS: Typical appearance for COVID-19 on CT images were found in 24 of 29 COVID-19 cases and 21 of 168 non-COVID-19 cases, according to the Radiological Society of North America Expert Consensus Statement (for predicting COVID-19, sensitivity 0.828, specificity 0.875, positive predictive value 0.533, negative predictive value 0.967). When we focused on cases with typical CT images, loss of taste or smell, and close contact with COVID-19 patients were exclusive characteristics for the COVID-19 cases. Among laboratory data, high fibrinogen (P < 0.01) and low white blood cell count (P < 0.01) were good predictors for COVID-19 with typical CT images in multivariate analysis. CONCLUSIONS: In a relatively low prevalence region, CT screening has high sensitivity to COVID-19 in patients with suspected symptoms. When chest CT findings are typical for COVID-19, close contact, loss of taste or smell, lower white blood cell count, and higher fibrinogen are good predictors for COVID-19.

Blood Glucose Control Strategy for Type 2 Diabetes Patients With COVID-19.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus has spread all over the world affecting tens of millions of people. Another pandemic affecting the modern world, type 2 diabetes mellitus is among the major risk factors for mortality from COVID-19. Current evidence, while limited, suggests that proper blood glucose control may help prevent exacerbation of COVID-19 even in patients with type 2 diabetes mellitus. Under current circumstances where the magic bullet for the disease remains unavailable, it appears that the role of blood glucose control cannot be stressed too much. In this review the profile of each anti-diabetic agent is discussed in relation to COVID-19.

NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer.

Small cell lung cancer (SCLC) is a high-grade malignancy, and treatment strategies have not changed for decades. In this study, we searched for novel targets for antibody-drug conjugate (ADC) therapy for SCLC. We identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1 (NRXN1). The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines (SHP77 and NCI-H526). The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumor activity in SCLC cell lines. Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumor activity of NRXN1-mediated ADC therapy. Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.

Integrin α11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11ß1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence-free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.

Identification of a metastatic lung adenocarcinoma of the palate mucosa through genetic and histopathological analysis: a rare case report and literature review.

BACKGROUND: Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs. CASE PRESENTATION: A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD. CONCLUSIONS: A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.

Prevalence of bone pain decreases as lymph node stage increases in nonsmall cell lung cancer patients.

According to lung cancer guidelines, positron emission tomography scan is recommended for initial evaluation of bone metastasis. However, guidelines differ in their recommendations for when it should be used. We investigated the appropriate use of bone imaging in nonsmall cell lung cancer (NSCLC) patients. One hundred seventy-seven consecutive NSCLC patients who had distant metastases at presentation and were admitted between January 2012 and April 2016 were retrospectively reviewed. Among patients with bone metastases, we explored bone pain, number of bone metastases, location of bone metastases, and clinical tumor (T) and lymph node (N) classification. Sixty-three patients had bone metastases. There was a trend toward an increase in prevalence of bone metastases as lymph node stage increased. The prevalence of bone pain significantly decreased as N stage increased (p = 0.017). N0 and N2-3 patients were more likely to have multiple bone metastases (p = 0.038). Compared with patients who had a single bone metastasis, patients with multiple metastases had a significantly higher probability of having at least 1 bone metastasis located in the thorax or upper abdomen. All N0 patients have at least 1 bone metastasis in the thorax or upper abdomen. Clinical N0 NSCLC patients with bone metastasis are likely to have bone pain and have multiple bone metastases. N2-3 patients are more likely to have bone metastases but less likely to have bone pain. If NSCLC patients do not have bone pain, and CT of the chest and upper abdomen does not reveal any lymph node or bone metastasis, further survey for bone metastases may be omitted; bone imaging should be performed in N2 and N3 patients regardless of symptoms.

Mean platelet volume and lymphocyte-to-monocyte ratio are associated with shorter progression-free survival in EGFR-mutant lung adenocarcinoma treated by EGFR tyrosine kinase inhibitor.

BACKGROUND: A growing body of evidence supports the role of platelets in cancer metastasis, escape from immune surveillance, and angiogenesis. Mean platelet volume (MPV), which reflects platelet turnover, is reported routinely as part of automated complete blood count. Accumulating evidence suggests that MPV is a useful biomarker in several diseases including cancer. However, its role in cancer patients receiving molecular targeted therapy has not been described in the literature. MATERIALS AND METHODS: We retrospectively analysed the prognostic impact of MPV in advanced or recurrent EGFR mutant lung adenocarcinoma treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). Lymphocyte-to-monocyte ratio (LMR) has been previously reported to be a poor prognostic factor in EGFR mutant non-small cell lung cancer and was also included as a covariate. RESULTS: Using the previously described Cutoff Finder algorithm, the cut-off points for MPV and LMR that best predicted progression free survival (PFS) of EGFR-TKI were determined as 10.3 and 2.8, respectively. The median PFS was 14.7 and 8.2 months in MPV low and high groups (p = 0.013, log-rank test). The median PFS was 13.5 and 6.2 months in LMR high and low groups (p < 0.001, log-rank test). MPV and LMR were independently distributed (chi square test) and the multivariate analysis using Cox's proportional hazards regression model revealed that high MPV, low LMR, and pleural effusion were significant predictors for shorter PFS. CONCLUSION: MPV and LMR, measured as part of routine complete blood count, can be utilized to predict the outcome of EGFR-TKI therapy with no additional costs. Our results suggest a mechanism of EGFR-TKI resistance which is associated with the functional status of the platelets.

Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma.

Adenosine-to-inosine (A-to-I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have shown several microRNAs that undergo A-to-I editing in human cancers, some of which have been reported to be associated with prognosis. Herein, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico in order to identify A-to-I microRNA editing events. Editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in AD than in NC and, in a large number of cases, the editing level of miR-200b-3p was higher in AD than in NC. Difference in the editing level between AD and NC was largest for miR-99a-5p. Then, we examined the editing level of miR-99a-5p in 50 surgically resected lung adenocarcinoma cases at our institution by a conventional sequence-based method, and its association with clinical outcomes. The editing level of miR-99a-5p was significantly lower in 19 cases of AD (38%) than in corresponding NC. These cases showed a shorter overall survival as assessed using the log-rank test (P = .047). This trend was consistent with previous analyses of TCGA dataset. The altered editing level of microRNAs in lung adenocarcinoma could serve as a potential biomarker.

Cerebral Arterial Air Embolism after Diagnostic Flexible Fiberoptic Bronchoscopy: A Case Report and Review of the Literature.

Cerebral arterial air embolism (CAAE) is an extremely rare complication of diagnostic flexible fiberoptic bronchoscopy, reported to occur once about every 103978 examinations. In all the eight cases of CAAE reported previously, the patients had undergone transbronchial lung biopsy (TBLB) or transbronchial needle aspiration (TBNA) prior to the onset of CAAE. Herein, we describe the case of a 77-year-old patient with double primary lung cancer who developed CAAE after bronchial curette cytology, which is considered to be less invasive than TBLB or TBNA. The patient was treated with supplemental oxygen, but paresis of the left upper arm and left spatial neglect remained. This is the first report of CAAE occurring after bronchial curettage during diagnostic flexible fiberoptic bronchoscopy.

Early stage non-small cell lung cancer patients need brain imaging regardless of symptoms.

BACKGROUND: Japanese Lung Cancer Society and ESMO guideline recommends screening for brain metastasis in all patients with non-small cell lung cancer (NSCLC), while NCCN/ACCP guidelines do not recommend screening patients who are asymptomatic and with clinical stage I NSCLC. However, brain metastasis sometimes occurs in early stage NSCLC patients without any neurological symptoms. METHODS: We retrospectively reviewed medical records of 124 patients admitted to the University of Tokyo Hospital with stage IV NSCLC from January 2012 to April 2016. We analyzed clinical stage, the presence of the central nervous system manifestations and the number of brain metastases. RESULTS: Forty-six out of 124 cases had brain metastasis at presentation. The brain metastasis group had larger number of female, never smokers and patients with EGFR mutation compared with extracranial metastasis group. Twenty-one of 35 adenocarcinoma cases with brain metastasis had EGFR mutations. Out of 46 brain metastasis patients, 29 patients (63%) were asymptomatic and patients with EGFR mutations were significantly less likely to have neurological symptoms (4/21 vs. 7/14, p = 0.049). Six out of 46 cases with brain metastasis (13%) were clinical T1-2aN0. In clinical T1-2aN0 cases, only one patient had neurological symptoms at presentation. CONCLUSION: In clinical T1-2aN0 lung cancer patients with brain metastasis, almost all patients were asymptomatic. Patients with EGFR mutations and brain metastasis were likely to be asymptomatic. Regardless of central nervous system symptoms, routine brain imaging seems warranted in all NSCLC patients, especially in areas where patients have a higher frequency of EGFR mutations.

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma.

BACKGROUND: Cisplatin is a key drug for treating lung adenocarcinoma, and its sensitivity to cisplatin is directly related to prognosis. We aimed to reveal the roles of genes related to glutathione synthesis (glutamate-cysteine ligase catalytic subunit, GCLC) and cystine uptake (cystine/glutamate transporter, xCT and CD44v8-10) in cisplatin resistance and prognosis in lung adenocarcinoma. METHODS: We established cell lines stably expressing GCLC, xCT, standard isoform of CD44, and CD44v8-10, and investigated their sensitivities to cisplatin. We also measured mRNA expression levels of these genes in the tumor tissues from 92 lung adenocarcinoma patients. Patients were divided into high-expression (upper quartile, N = 23) and low-expression groups (remaining patients, N = 69). Recurrence-free survival, overall survival (N = 92), and post-recurrence survival (N = 22) were selected as endpoints. RESULTS: Compared with the control green fluorescent protein-expressing cell line (inhibitory concentration 50:6.9 µM), all the stable cell lines were more resistant to cisplatin (12.9 µM, P = 0.025; 13.9 µM, P = 0.028; 26.7 µM, P = 0.001; 17.7 µM, P = 0.008, respectively). In contrast, there was no significant difference in recurrence-free or overall survival between the high- and low-expression groups for any of the genes. However, high expression of GCLC was a risk factor for poorer post-recurrence survival (hazard ratio, 6.26; 95% confidence interval, 1.37-28.7; P = 0.018). CONCLUSION: High expression levels of genes related to glutathione synthesis and cystine uptake promote cisplatin resistance in lung adenocarcinoma cell lines. High expression of GCLC in tumor tissue may be a potential predictor of treatment failure.

Old age and underlying interstitial abnormalities are risk factors for development of ARDS after pleurodesis using limited amount of large particle size talc.

BACKGROUND AND OBJECTIVE: Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. METHODS: We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. RESULTS: Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. CONCLUSION: Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.

Acute Arterial Thrombosis during Postoperative Adjuvant Cisplatin-based Chemotherapy for Completely Resected Lung Adenocarcinoma.

A malignant tumor can cause hypercoagulation and it also often coexists with thrombosis. Cisplatin-based chemotherapy can also induce adverse vascular effects, including arterial thrombosis. We herein report a case of acute arterial thrombosis in a patient undergoing postoperative adjuvant cisplatin-based chemotherapy for completely resected lung cancer. The patient complained of acute leg pain after chemotherapy, and computed tomography revealed multiple thrombi from the thoracic to popliteal arteries. Arterial thrombosis during adjuvant chemotherapy is extremely rare; however, careful clinical observation of patients receiving cisplatin-based chemotherapy is important, because arterial thrombosis, even in the absence of the primary malignant tumor, is possible.

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.