In conclusion we have shown that the cellular
In conclusion, we have shown that the cellular effects produced by SFN in NSCLC Iohexol are largely mediated by SFN-induced production of ROS. Cells with higher levels of EGFR were more resistant to SFN treatment and showed resistance to SFN-induced apoptosis, suggesting that high EGFR levels protect cells from SFN-induced apoptosis (Fig. 4E).
Conflict of Interest
Acknowledgments This work was supported by grants from Chang Gung Memorial Hospital (CMRPF1H0011 to C.Y. Chen), Chang Gung University of Science and Technology (ZRRPF3H0091 to C.Y. Chen), and the Ministry of Science and Technology of Taiwan (106-2320-B-255-006 to C.Y. Chen). The funders had no role in study design, data collection, data analysis, publication decisions, or manuscript preparation.
Introduction Lung cancer is one of the leading causes of death worldwide. More than 85% of lung cancers are non-small cell lung cancer (NSCLC); adenocarcinoma is the most common subtype of NSCLC . Due to the lack of early specific signs and symptoms, most lung cancer patients are diagnosed at advanced stages and thus are not eligible for curative surgery; hence, the prognosis for these patients is usually poor . In the last decade, the advent of novel therapeutics that target genetically-altered signaling pathways has revolutionized treatment options for NSCLC patients . Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) targeted therapy has shown promising benefits for patients with advanced NSCLC. Mutations in the gene encoding EGFR are strong predictors of how well patients with advanced NSCLC will respond to EGFR TKIs [4,5]. CT-imaging plays an important role in diagnosing lung cancer and evaluating responses to treatment. Previous studies suggested that features of CT or CT-based radiomics may be associated with EGFR mutations [, , , , , , , , , ]. To date, most studies of CT-features or CT-based radiomics of EGFR mutations focused on early-stage and resectable NSCLC or on all stages of NSCLC. However, the main patient population that received EGFR TKI targeted therapy had advanced NSCLC. Additionally, different stages of NSCLC contain different CT-features. Furthermore, these studies mainly focused on primary tumors; only a few of them studied metastatic lesions or lymph nodes. However, development of lung cancer targeted therapies and validation of therapeutic response biomarkers will require analysis of both primary and metastatic cancers, based on evidence of intra-tumor genetic heterogeneity and genetic heterogeneity between primary and metastatic tumors in lung cancers [16,17].
Materials and methods
Discussion By univariate analysis, our study showed that EGFR mutations in advanced pulmonary adenocarcinomas were significantly associated with females, non-smokers, and absence of emphysema; however, subsequent multivariate analysis only confirmed the significance of absence of emphysema. Previous studies showed that EGFR mutations are more frequent in tumors with adenocarcinoma histology, in non-smokers or light smokers, and in women with NSCLC [10,11,18,19]. However, other studies reported no association between the presence of EGFR mutations and sex or non-smoking status [12,20]. The differences between these studies may have been due to the heterogenous pathologic profiles of the patients leading to selection bias, different research parameters, and different statistical methods (e.g., some of these studies did not use multivariate analysis). Numerous studies have shown that smoking is associated with emphysema and that both are risk factors for lung cancer; additionally, emphysema as a lung cancer risk factor may not be entirely dependent on smoking [, , , ]. Although squamous cell carcinoma is the most prevalent histopathological feature in emphysema- and smoking-related lung cancer, the presence of emphysema is also a risk factor for lung adenocarcinoma [23,24]. A large number of studies have investigated the correlation between smoking and EGFR mutations, but very few studies evaluated the correlation between emphysema and EGFR mutations . Thus, further studies that examine correlations between smoking, emphysema, and EGFR-mutated NSCLC are needed.