Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

Loss of E-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), can significantly affect metastatic dissemination. However, the molecular mechanism of EMT-associated metastatic dissemination by loss of E-cadherin still remains unclear in non-small cell lung cancers (NSCLCs). In the present study, we show that the knockdown of E-cadherin was sufficient to convert A549 NSCLC cells into mesenchymal type with the concurrent up-regulation of typical EMT inducers such as ZEB1 and TWIST1. Interestingly, the EMT-induced cells by E-cadherin depletion facilitate invasion in a matrix metalloproteinase-2 (MMP2)-dependent manner with aberrant activation of EGFR signaling. We demonstrated that the elevated invasiveness was a result of the activated EGFR-MEK/ERK signaling, which in turn leads to ZEB1 dependent MMP2 induction. These results suggest that the EGFR-MEK/ERK/ZEB1/MMP2 axis is responsible for promoted invasion in EMT-induced NSCLCs. Consistently, ERK activation and loss of E-cadherin were both observed in the disseminating cancer cells at the invasive tumor fronts in NSCLC cancer tissues. Thereby, these data suggest that the EGFR-MEK/ERK signaling would be a promising molecular target to control aberrant MMP2 expression and consequent invasion in the EMT-induced NSCLCs

Quantitative imaging using radiomics can capture distinct phenotypic differences between tumors and may have predictive power for certain phenotypes according to specific genetic mutations. We aimed to identify the clinicoradiologic predictors of tumors with ALK (anaplastic lymphoma kinase), ROS1 (c-ros oncogene 1), or RET (rearranged during transfection) fusions in patients with lung adenocarcinoma.A total of 539 pathologically confirmed lung adenocarcinomas were included in this retrospective study. The baseline clinicopathologic characteristics were retrieved from the patients' medical records and the ALK/ROS1/RET fusion status was reviewed. Quantitative computed tomography (CT) and positron emission tomography imaging characteristics were evaluated using a radiomics approach. Significant features for the fusion-positive tumor prediction model were extracted from all of the clinicoradiologic features, and were used to calculate diagnostic performance for predicting 3 fusions' positivity. The clinicoradiologic features were compared between ALK versus ROS1/RET fusion-positive tumors to identify the clinicoradiologic similarity between the 2 groups.The fusion-positive tumor prediction model was a combination of younger age, advanced tumor stage, solid tumor on CT, higher values for SUV(max) and tumor mass, lower values for kurtosis and inverse variance on 3-voxel distance than those of fusion-negative tumors (sensitivity and specificity, 0.73 and 0.70, respectively). ALK fusion-positive tumors were significantly different in tumor stage, central location, SUV(max), homogeneity on 1-, 2-, and 3-voxel distances, and sum mean on 2-voxel distance compared with ROS1/RET fusion-positive tumors.ALK/ROS1/RET fusion-positive lung adenocarcinomas possess certain clinical and imaging features that enable good discrimination of fusion-positive from fusion-negative lung adenocarcinomas.

The prevalence of lung cancer has been increasing in healthy elderly patients with preserved pulmonary function and without underlying lung diseases. We aimed to determine the prevalence of and risk factors for postoperative pulmonary complications (PPCs) in healthy elderly patients with non-small cell lung cancer (NSCLC) to select optimal candidates for surgical resection in this subpopulation. We included 488 patients older than 70 years with normal spirometry results who underwent curative resection for NSCLC (stage IA-IIB) between 2012 and 2016. The median (interquartile range) age of our cohort was 73 (71–76) years. Fifty-two patients (10.7%) had PPCs. Severe PPCs like acute respiratory distress syndrome, pneumonia, and respiratory failure had prevalences of 3.7, 3.7, and 1.4%, respectively. Compared to patients without PPCs, those with PPCs were more likely to be male and current smokers; have a lower body mass index (BMI), higher American Society of Anesthesiologists (ASA) classification, more interstitial lung abnormalities (ILAs), and higher emphysema index on computed tomography (CT); and have undergone pneumonectomy or bilobectomy (all p < 0.05). On multivariate analysis, ASA classification ≥3, lower BMI, ILA, and extent of resection were independently associated with PPC risk. The short-term all-cause mortality was significantly higher in patients with PPCs. Curative resection for NSCLC in healthy elderly patients appeared feasible with 10% PPCs. ASA classification ≥3, lower BMI, presence of ILA on CT, and larger extent of resection are predictors of PPC development, which guide treatment decision-making in these patients.