scholarly journals A TAZ-AXL-ABL2 Feed-Forward Signaling Axis Promotes Lung Adenocarcinoma Brain Metastasis

Cell Reports ◽  
2019 ◽  
Vol 29 (11) ◽  
pp. 3421-3434.e8 ◽  
Author(s):  
Jacob P. Hoj ◽  
Benjamin Mayro ◽  
Ann Marie Pendergast
Keyword(s):  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Feed Forward ◽  
Signaling Axis

Micropapillary predominance is a risk factor for brain metastasis in resected lung adenocarcinoma

2021 ◽  
Author(s):  
Takao Shigenobu ◽  
Yusuke Takahashi ◽  
Yohei Masugi ◽  
Ryutaro Hanawa ◽  
Hirokazu Matsushita ◽  
...  
Keyword(s):  
Risk Factor ◽  
Brain Metastasis ◽  
Lung Adenocarcinoma

scholarly journals Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Wang ◽  
Chao Bian ◽  
Di Xia ◽  
Jin-Xi He ◽  
Ping Hai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Carcinoembryonic Antigen ◽  
Roc Curve ◽  
Univariate Analysis ◽  
Significant Risk ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Increased Risk

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

scholarly journals lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

2021 ◽  
Author(s):  
Weili Min ◽  
Liangzhang Sun ◽  
Burong Li ◽  
Xiao Gao ◽  
Shuqun Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Metastatic Potential ◽  
Caspase 8 ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Signaling Axis ◽  
Lung Adenocarcinoma Cells ◽  
Paclitaxel Liposome

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.

scholarly journals CMET-30. COMPREHENSIVE METHYLOME ANALYSIS OF EGFR-MUTANT PRIMARY LUNG ADENOCARCINOMA AND MATCHED BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi58-vi58
Author(s):  
Yasin Mamatjan ◽  
Michael Cabanero ◽  
Jeffrey Zuccato ◽  
Jessica Weiss ◽  
Shirin Karimi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Methylation Status ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Promoter Regions ◽  
Primary Lung Adenocarcinoma ◽  
Egfr Mutant

Abstract Brain metastasis (BM) in patients with EGFR-mutant lung adenocarcinoma is a major determinant of overall survival. Novel insight into the genetic and epigenetic underpinnings of BM development is lacking. The aim of this study is to compare the methylome of EGFR-mutant primary lung adenocarcinoma (EGFRM-PLA) and matched BM to identify important alterations for the mechanisms of BM. Matched EGFRM-PLA and BM tumors from seven patients were profiled using the Illumina Infinium MethylationEPIC BeadChip array. Unsupervised clustering analyses of the 14 samples showed a similar whole DNA methylation signatures between EGFRM-PLA and BM tumors. Furthermore, PCA plot highlighted that seven matched BM and lung tumor samples were clustered together closely based on matching pairs for the most variable probes (2.5K to 10K). These observations indicate high level of concordance and the same cell of origin. However, these fourteen samples clustered into two groups based on tumor site being lung or brain based on 83K differentially methylated CpG sites. Of the 83K probes, 2.4K were either hypermethylated or hypomethylated in all lung samples. A quarter of these 2.4K probes were located in promoter regions. Specifically, we identified differences in methylation status of EGFR/ALK promoter regions in lung tumors versus BM. CNV analyses showed higher deep deletions of chromosomes and genes in BM compared to EGFRM-PLA. Leukocytes unmethylation for purity (LUMP) scores which indicate immune cell infiltration were similar between lung and BM pairs (Mean LUMP_score=0.64) consistent with high immune cell infiltration. Our results indicated a similar whole DNA methylation signature of EGFRM-PLA and matched BM, while comprehensive analysis identified important differentially methylated probes. Distinct differences in CNV alterations were observed in lung versus brain samples. The BM and EGFRM-PLA showed similar tumor purity and immune cell components. Overall, tumor methylation profiling provides clinically important information regarding biology of BM in EGFRM-PLA.

scholarly journals Development and validation of a five‐gene model to predict postoperative brain metastasis in operable lung adenocarcinoma

2020 ◽  
Vol 147 (2) ◽  
pp. 584-592
Author(s):  
Fangqiu Fu ◽  
Yang Zhang ◽  
Zhendong Gao ◽  
Yue Zhao ◽  
Zhexu Wen ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Gene Model ◽  
Development And Validation
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