scholarly journals Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma

2021 ◽  
Author(s):  
Han Liang ◽  
Jianlian Deng ◽  
Tian Luo ◽  
Huijuan Luo ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Principal Component ◽  
Progression Free Survival ◽  
Chromatin Accessibility ◽  
Smoking History ◽  
Molecular Characteristics ◽  
Open Chromatin ◽  
Free Survival ◽  
Glycosphingolipid Biosynthesis ◽  
Chromatin Patterns

Abstract Considerable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet studies of open chromatin patterns associated with LUAD progression caused by smoking are still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network and pathway analysis was conducted for potential pathways identification. We identified a set of peaks that discriminated smokers in LUAD patients according to levels of exposure to tobacco quantified in pack-years, and also significantly associated with progression-free survival and overall survival of these patients. We then investigated the gene set related to those peaks and found that the comprising genes are strongly associated with LUAD development, such as B3GNT3, ACTN4 and CLDN3. They are consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways. In summary, our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

scholarly journals Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma

2021 ◽  
Author(s):  
Han Liang ◽  
Jianlian Deng ◽  
Tian Luo ◽  
Huijuan Luo ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Principal Component ◽  
Progression Free Survival ◽  
Chromatin Accessibility ◽  
Smoking History ◽  
Molecular Characteristics ◽  
Open Chromatin ◽  
Free Survival ◽  
Glycosphingolipid Biosynthesis ◽  
Chromatin Patterns

Abstract Considerable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet studies of open chromatin patterns associated with LUAD progression caused by smoking are still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network and pathway analysis was conducted for potential pathways identification. We identified a set of peaks that discriminated smokers in LUAD patients according to levels of exposure to tobacco quantified in pack-years, and also significantly associated with progression-free survival and overall survival of these patients. We then investigated the gene set related to those peaks and found that the comprising genes are strongly associated with LUAD development, such as B3GNT3, ACTN4 and CLDN3. They are consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways. In summary, our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

scholarly journals Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma

2020 ◽  
Author(s):  
Han Liang ◽  
Jianlian Deng ◽  
Tian Luo ◽  
Huijuan Luo ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Principal Component ◽  
Chromatin Accessibility ◽  
Smoking History ◽  
Molecular Characteristics ◽  
Open Chromatin ◽  
Independent Dataset ◽  
Glycosphingolipid Biosynthesis ◽  
Chromatin Patterns

AbstractConsiderable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet study of open chromatin patterns associated with LUAD progression caused by smoking is still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network and pathway analysis was conducted for potential pathways identification. Results were verified in an independent dataset from primary LUAD samples. We identified a set of peaks that clearly differentiated long-term from short-term smokers in LUAD patients and also significantly associated with overall survival of these patients. We then investigated the gene set related to those peaks and found that the comprising genes are strongly associated with LUAD development, such as B3GNT3, ACTN4 and CLDN3. They are consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways.In summary, our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

scholarly journals Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejun He ◽  
Jijun You ◽  
Haibing Ding ◽  
Zhisheng Zhang ◽  
Lin Cui ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Therapy ◽  
Vasculogenic Mimicry ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Background Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. Methods This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People’s Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). Results Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90–1095) days, and 45 patients with VM had a median PFS of 167 (range, 90–369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10–1.71), N stage (HR = 1.43, 95%CI: 1.09–1.86), M stage (HR = 2.85, 95%CI: 1.76–4.61), differentiation (HR = 1.85, 95%CI: 1.29–2.65), therapy (HR = 0.32, 95%CI: 0.21–0.49), VM (HR = 2.12, 95%CI: 1.33–3.37), and ECOG (HR = 1.41, 95%CI: 1.09–1.84) were independently associated with PFS. Conclusion The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.

Mature tertiary lymphoid structures in lung adenocarcinoma are associated with better progression free survival

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S149-S149
Author(s):  
R Obeng ◽  
V Parihar ◽  
D Alexis ◽  
M Behera ◽  
T Owonikoko ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Germinal Centers ◽  
Disease Stage ◽  
Free Survival ◽  
Formalin Fixed Paraffin Embedded ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Lymphoid Aggregates

Abstract Introduction/Objective The presence of inducible lymphoid structures known as tertiary lymphoid structures in the tumor microenvironment has been shown to correlate with positive clinical outcome. However, the maturation states of lymphoid aggregates in lung adenocarcinoma are not completely understood. Methods/Case Report Seventy tumor samples from 69 patients diagnosed with lung adenocarcinoma (Stages I to III) between 2013 and 2015 were included in the study. The presence and maturation states of the lymphoid structures within the tumors were evaluated by conventional and 26 samples were further analyzed by multiplexed immunohistochemistry of formalin fixed paraffin embedded tissues and then quantified. Mature lymphoid follicles containing germinal centers were identified by the presence of CD21+ and BCL-6+ cells in an organized configuration within tight clusters of T and B cells. Results (if a Case Study enter NA) Samples with fully mature lymphoid structures (germinal centers) had larger tumors and higher disease stage. The number of mature lymphoid structures correlated with the total number of lymphoid aggregates present in the tumor microenvironment. Additionally, tumor samples with ≥10 mature lymphoid structures had more primary follicles. While there was no difference in overall survival, progression free survival was significantly longer in patients who had ≥10 mature lymphoid structures in comparison with patients who had &lt;10 mature structures. Conclusion In conclusion, a spectrum of lymphoid aggregates in different stages of maturation are present in lung adenocarcinoma. An increase in the number of mature lymphoid structures may be associated with progression free survival in patients with lung adenocarcinoma.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting

2021 ◽  
Author(s):  
Ming-Wei Chen Ming-Wei Chen ◽  
An-Tai He . ◽  
Yi Pei .
Keyword(s):  
Lung Adenocarcinoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
First Line ◽  
Free Survival ◽  
Mean Survival Time ◽  
First Line Therapy ◽  
To Receive

Abstract BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

scholarly journals Blood Cadmium Level Is Associated with Short Progression-Free Survival in Nasopharyngeal Carcinoma

2019 ◽  
Vol 16 (16) ◽  
pp. 2952 ◽  
Author(s):  
Taifeng Du ◽  
Wenlong Huang ◽  
Shukai Zheng ◽  
Mian Bao ◽  
Yuanni Huang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Cadmium Exposure ◽  
Smoking History ◽  
Cadmium Level ◽  
Clinical Factors ◽  
Free Survival ◽  
Kaplan Meier ◽  
Blood Cadmium

The prognosis of nasopharyngeal carcinoma (NPC) is poor with disease progression. Cadmium exposure is a risk factor for NPC. We aimed to investigate the effect of cadmium exposure, by measuring cadmium level, and clinicopathologic factors on NPC disease progression and prognosis. A total of 134 NPC cases were analyzed and venous blood samples were collected. Blood cadmium level was analyzed by graphite furnace atomic absorption spectrophotometry. Clinical data were collected at baseline for patients and tumor characteristics from medical records. Progression-free survival (PFS) was analyzed during follow-up. The effect of cadmium exposure and clinical factors on PFS was analyzed by the Kaplan–Meier method and Cox regression models. Blood cadmium level was associated with history of disease and smoking history and pack-years. On Kaplan–Meier analysis, a high blood cadmium level, male sex, smoking history and increasing pack-years, as well as advanced clinical stage were all associated with short PFS. On multivariate analysis, blood cadmium level was an independent risk factor and predictor of NPC prognosis and disease progression. Cadmium exposure and related clinical factors can affect the prognosis of NPC, which merits further study to clarify.

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