• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6449-6453
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• 2014

Background: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. Materials and Methods: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/(total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. Results: The mean survival time for each tertile was: for the $1^{st}$ 9.8 months (95%CI:7.765-11.848), $2^{nd}$ 15.4 months (95%CI:12.685-18.186), and $3^{rd}$ 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. Conclusions: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.72-77
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• 2000

A proper pathologic diagnosis of small cell lung cancer(SCLC) is essential for the application of aggressive treatment modalities. However, various authors have suggested several subtypes of SCLC based on morphological features. Among them, the incidence of small cell lung cancer(SCLC) combined with squamous cell and/or adenocarcinoma, represents less than 1% to 3% of all SCLC tumors. Because of the rarity of SCLC combined with squamous cell and/or adenocarcinoma, very little is known about its clinical characteristics and response to therapy. We report a case of SCLC combined with squamous cell and adenocarcinoma in a 68 year old male who experienced pneumonectomy of the left lung.

• Journal of Chest Surgery
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• v.52 no.5
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• pp.342-352
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• 2019

Background: Smokers with lung adenocarcinoma have a worse prognosis than those who have never smoked; the reasons for this are unclear. We aimed to elucidate the impact of smoking on patients' prognosis and the association between smoking and clinicopathologic factors, particularly histologic subtypes. Methods: We reviewed the records of 233 patients with pathologic stage T1-4N0-2M0 lung adenocarcinomas who underwent surgery between January 2004 and July 2015. The histologic subtypes of tumors were reassessed according to the 2015 World Health Organization classification. Results: In total, 114 patients had a history of smoking. The overall survival probabilities differed between never-smokers and ever-smokers (80.8% and 65.1%, respectively; p=0.003). In multivariate analyses, the predominant histologic subtype was an independent poor prognostic factor. Smoking history and tumor size >3 cm were independent predictors of solid or micropapillary (SOL/MIP)-predominance in the logistic regression analysis. Smoking quantity (pack-years) in patients with SOL/MIP-predominant tumors was greater than in those with lepidic-predominant tumors (p=0.000). However, there was no significant difference in smoking quantity between patients with SOL/MIP-predominant tumors and those whose tumors had non-predominant SOL/MIP components (p=0.150). Conclusion: Smoking was found to be closely associated with SOL/MIP-predominance in lung adenocarcinoma. Greater smoking quantity was related to the presence of a SOL/MIP component.

• Molecules and Cells
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• v.42 no.2
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• pp.161-165
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• 2019

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and has high rates of metastasis. Transforming growth factor beta-inducible protein (TGFBI) is an extracellular matrix component involved in tumour growth and metastasis. However, the exact role of TGFBI in NSCLC remains controversial. Gene silencing via DNA methylation of the promoter region is common in lung tumorigenesis and could thus be used for the development of molecular biomarkers. We analysed the methylation status of the TGFBI promoter in 138 NSCLC specimens via methylation-specific PCR and evaluated the correlation between TGFBI methylation and patient survival. TGFBI promoter methylation was detected in 25 (18.1%) of the tumours and was demonstrated to be associated with gene silencing. We observed no statistical correlation between TGFBI methylation and clinicopathological characteristics. Univariate and multivariate analyses showed that TGFBI methylation is significantly associated with poor survival outcomes in adenocarcinoma cases (adjusted hazard ratio = 2.88, 95% confidence interval = 1.19-6.99, P = 0.019), but not in squamous cell cases. Our findings suggest that methylation in the TGFBI promoter may be associated with pathogenesis of NSCLC and can be used as a predictive marker for lung adenocarcinoma prognosis. Further large-scale studies are needed to confirm these findings.

• Journal of Yeungnam Medical Science
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• v.34 no.2
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• pp.270-274
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• 2017

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.

• Tuberculosis and Respiratory Diseases
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• v.72 no.2
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• pp.203-206
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• 2012

Cystic lesions or progressive cystic changes in adenocarcinoma of the lung have rarely been reported. We report a case of lung adenocarcinoma that progressed from ground-glass opacities (GGOs) and consolidations or nodules to extensive cystic lesions during 12 months in a young adult patient. A 29-year-old male was initially diagnosed with primary lung adenocarcinoma by transbronchial lung biopsy of the right lower lobe and lung to lung metastasis in both lungs according to imaging findings. The initial chest computed tomography (CT) scans showed multifocal GGOs, consolidations, and nodules in both lungs. Despite treatment with palliative chemotherapy, the patient's follow-up CT scans showed multiple, cystic changes in both lungs and that the lesions had progressed more extensively. He died of hypoxic respiratory failure one year after his diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3695-3700
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• 2012

Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research goups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.647-652
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• 2015

Background: Lung cancer was one of the most common cancers in both men and women all over the world. In this study, we aimed to clarify who could survive after long term chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: We enrolled 186 patients with stage IV NSCLC after long term chemotherapy from Jun 2006 to Nov 2014 diagnosed in Jiangsu Cancer Hospital. Multiple variables like age, gender, smoking, histology of adenocarcinoma and squamous-cell cancer, number of metastatic sites, metastatic sites (e.g. lung, brain, bone, liver and pleura), hemoglobin, lymphocyte rate (LYR), Change of LYR during multiple therapies, hypertension, diabetes, chronic bronchitis, treatments (e.g.radiotherapy and targeted therapy) were selected. For consideration of factors influencing survival and response for patients with advanced NSCLC, logistic regression analysis and Cox regression analysis were used in an attempt to develop a screening module for patients with elevated survival after long term chemotherapy become possible. Results: Of the total of 186 patients enrolled, 69 survived less than 1 year (short-term group), 45 one to two years, and 72 longer than 3 years (long-term group). For logistic regression analysis, the short-term group was taken as control group and the long-term group as the case group. We found that age, histology of adenocarcinoma, metastatic site (e.g. lung and liver), treatments (e.g. targeted therapy and radiotherapy), LYR, a decreasing tendency of LYR and chronic bronchitis were individually associated with overall survival by Cox regression analysis. A multivariable Cox regression model showed that metastatic site (e.g. lung and liver), histology of adenocarcinoma, treatments (e.g. targeted therapy and radiotherapy) and chronic bronchitis were associated with overall survival. Thus metastatic site (e.g. lung and liver) and chronic bronchitis may be important risk factors for patients with advanced NSCLC. Gender, metastatic site (e.g. lung and liver), LYR and the decreasing tendency of LYR were significantly associated with long-term survival in the individual-variable logistic regression model (P<0.05). On multivariate logistic regression analysis, gender, metastatic site (e.g. lung and liver) and the decreasing tendency of LYR associated with long-term survival. Conclusions: In conclusion, female patients with stage IV adenocarcinoma of NSCLC who had decreasing tendency of LYR during the course therapy and had accepted multiple therapies e.g. more than third-line chemotherapy, radiotherapy and/or targeted therapy might be expected to live longer.

• Journal of Chest Surgery
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• v.53 no.5
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• pp.250-257
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• 2020

Background: Lung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD. Methods: LUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in nonGGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted. Results: Overall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation. Conclusion: In conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.