Global Histone Modifications Predict Prognosis of Resected Non–Small-Cell Lung Cancer

2007 ◽  
Vol 25 (28) ◽  
pp. 4358-4364 ◽  
Author(s):  
Fabrice Barlési ◽  
Giuseppe Giaccone ◽  
Marielle I. Gallegos-Ruiz ◽  
Anderson Loundou ◽  
Simone W. Span ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Histone Modifications ◽  
Small Cell ◽  
Epigenetic Changes ◽  
Small Cell Lung ◽  
Histone 3 ◽  
Nsclc Patients

PurposeEpigenetic modifications may contribute to the development and progression of cancer. We investigated whether epigenetic changes involving multiple histones influence prognosis of non–small-cell lung cancer (NSCLC) patients.Patients and MethodsWe used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12, histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 in resected tumor samples of 138 NSCLC patients. Data were analyzed using a recursive partitioning analysis (RPA).ResultsThe RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology, and histone modifications: H3K4diMe (< or ≥ 85% tumor cells), H3K9Ac (< or ≥ 68% tumor cells), and H2AK5Ac (< or ≥ 5% tumor cells). The seven groups were associated with significantly different disease-free (P < .0001) and overall survival (P < .0001). Interestingly, the four groups determined by stage I patients (below the first node) displayed dramatic differences in survival (median, 10 months in adenocarcinoma patients with H3K9Ac ≥ 68% v 147 months in nonadenocarcinoma patients with H3K4diMe ≥ 85%). A Cox model retained age and RPA groups as the sole independent factors significantly influencing overall survival.ConclusionThe prognostic influence of epigenetic changes involving multiple histones, in particular H2A and H3, is greater in early NSCLC, and evaluation of these changes may help in selecting early-stage NSCLC patients for adjuvant treatment. Our observations provide a rationale for the use of a combination of standard chemotherapy with drugs interacting with histone modifications, such as histone deacetylase inhibitors.

Global histone modifications predict prognosis of resected non-small cell lung cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7662-7662
Author(s):  
F. Barlesi ◽  
G. Giaccone ◽  
M. I. Gallegos-Ruiz ◽  
A. Loundou ◽  
S. W. Span ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Histone Modifications ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Histone 3 ◽  
Nsclc Patients

7662 Background: Epigenetic modifications, such as methylation and/or acetylation of histones, may contribute to the development and progression of cancer. We investigated whether histone modifications influence prognosis of non-small cell lung cancer (NSCLC). Methods: We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12 (H2BK12Ac), histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 (H4K8Ac), in resected tumor samples of 138 NSCLC patients. In addition, the genotype of a tandem repeat polymorphism in the histone 3 methyltransferase SMYD3 gene was determined using PCR and capillary electrophoresis. Data were analyzed using a recursive partitioning analysis (RPA). Results: The overall median expression of H3K4diMe, H2AK5Ac, H2BK12Ac, H3K9Ac, and H4K8Ac were 75, 10, 0, 25, and 80%, respectively. The RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology (second node) and histone modifications (third node). H3K4diMe (< or =85% tumor cells), H3K9Ac (< or =68% tumor cells) and H2AKAc (< or =5% tumor cells) were retained by RPA. The SMYD3 genotype was not retained by RPA. The seven groups were associated with significantly different disease- free (p<0.0001) and overall survival (p<0.0001). Interestingly, the four groups determined by stage I patients (below the first node) displayed dramatic differences in survival (median from 10 months in adenocarcinoma, H3K9Ac=68%, to 147 months in non-adenocarcinoma, H3K4diMe=85%). Conclusions: The prognostic influence of global histone modifications is greater in early stage NSCLC and it may help in the selection of early stage NSCLC patients for adjuvant treatment and provides a rationale for the use of combination of standard chemotherapy with drugs interacting with histone modifications such as histone deacetylases (HDAC) inhibitors. No significant financial relationships to disclose.

scholarly journals Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingyao Li ◽  
Yi Liao ◽  
Yaling Ran ◽  
Guiyu Wang ◽  
Wei Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Sensitivity And Specificity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
Nsclc Patients

Abstract Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

scholarly journals Molecular Characterization of Circulating Tumor Cells Enriched by A Microfluidic Platform in Patients with Small-Cell Lung Cancer

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 880 ◽  
Author(s):  
Eva Obermayr ◽  
Christiane Agreiter ◽  
Eva Schuster ◽  
Hannah Fabikan ◽  
Christoph Weinlinger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Epithelial Cell ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lineage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Poor Overall Survival ◽  
Blood Samples

At initial diagnosis, most patients with small-cell lung cancer (SCLC) present with metastatic disease with a high number of tumor cells (CTCs) circulating in the blood. We analyzed RNA transcripts specific for neuroendocrine and for epithelial cell lineages, and Notch pathway delta-like 3 ligand (DLL3), the actionable target of rovalpituzumab tesirine (Rova-T) in CTC samples. Peripheral blood samples from 48 SCLC patients were processed using the microfluidic Parsortix™ technology to enrich the CTCs. Blood samples from 26 healthy donors processed in the same way served as negative controls. The isolated cells were analyzed for the presence of above-mentioned transcripts using quantitative PCR. In total, 16/51 (31.4%) samples were CTC-positive as determined by the expression of epithelial cell adhesion molecule 1 (EpCAM), cytokeratin 19 (CK19), chromogranin A (CHGA), and/or synaptophysis (SYP). The epithelial cell lineage-specific EpCAM and/or CK19 gene expression was observed in 11 (21.6%) samples, and positivity was not associated with impaired survival. The neuroendocrine cell lineage-specific CHGA and/or SYP were positive in 13 (25.5%) samples, and positivity was associated with poor overall survival. DLL3 transcripts were observed in four (7.8%) SCLC blood samples and DLL3-positivity was similarly associated with poor overall survival (OS). CTCs in SCLC patients can be assessed using epithelial and neuroendocrine cell lineage markers at the molecular level. Thus, the implementation of liquid biopsy may improve the management of lung cancer patients, in terms of a faster diagnosis, patient stratification, and on-treatment therapy monitoring.

scholarly journals Factors Affecting the Survival of Patients with Oligometastatic Non-Small-Cell Lung Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Shi ◽  
Jianxin Yang ◽  
Ninghua Yao ◽  
Minghai Shao ◽  
Wenxiu Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Sensitivity Analysis ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Overall Survival Rate ◽  
Small Cell Lung ◽  
Nsclc Patients

Background. The aim was to investigate the potential factors related with overall survival of oligometastatic non-small-cell lung cancer (NSCLC) patients. Methods. A literature search was conducted in databases including PubMed, Embase, and Cochrane library up to March 2017. The hazard radio (HR) as well as the corresponding 95% confidence interval (CI) were calculated, and all the statistics analysis was performed by the R 3.12. Heterogeneity was analyzed using I-squared and Cochran Q tests. Furthermore, sensitivity analysis was performed to evaluate the stability of results. Results. In total, 6 articles were included in the meta-analysis. Nodal status was significantly correlated with the overall survival rate of NSCLC oligometastatic patients (HR: 1.69, 95% CI: 1.23–2.32, Z=3.20, P=0.001). No significant relationship was found between overall survival rate of NSCLC oligometastatic patients and the indicators including sex, stage, smoker, age, and histology. Notably, sensitivity analysis on data evaluating relationship between patients survival and the stage and histology showed that results were reversed after removing one of the studies. Conclusions. Nodal status might be associated with the overall survival of oligometastatic NSCLC patients.

Non-examination of lymph nodes (LN) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 8547-8547
Author(s):  
Ahmedin Jemal ◽  
Chun Chieh Lin ◽  
Matthew Smeltzer ◽  
Raymond U. Osarogiagbon
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lymph Nodes ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

A retrospective study of low-dose apatinib combined with S-1 in patients with advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20666-e20666
Author(s):  
Tong Zhou ◽  
Xiaoyue Zhou ◽  
Peng Li ◽  
Changling Wu ◽  
Changsong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Low Dose ◽  
Standard Treatment ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20666 Background: Currently regimen for advanced non-small cell lung cancer (NSCLC) failing from standard treatment is deficient. This retrospective study aimed to assess the efficacy and safety of low-dose apatinib in combination with S-1 therapy in this NSCLC setting. Methods: In this retrospective study, advanced NSCLC patients who failed from standard treatment in Changzhou Cancer Hospital of Soochow University were screened for eligibility. Progression-free survival (PFS) was set as the primary endpoint. Overall response rate (ORR), disease control rate (DCR), Overall survival (OS) and safety profile were considered to be the secondary endpoints. Results: 31 eligible patients were included in this study. The median PFS (mPFS) was 102 days (95% CI: 57-147). 7 patients (23%; 95% CI: 11-38%) achieved an objective response and the DCR was maintained in 23 patients (75%; 95% CI: 58-86%). The median OS (mOS) was 422 days (95% CI: 148-696).Patients with smoking had a tendency for shorter overall survival without significant differences (HR = 4.105, 95% CI: 0.874-19.288, P = 0.074). Treatment-related grade 3 toxicity was observed in five patients (16%) and the common grade 1 or 2 adverse events were fatigue (42%), hypertension (32%), and hand-foot-skin reaction (23%). Conclusions: Combination of low-dose apatinib and S-1 could be effective and tolerable for advanced NSCLC patients failed from standard treatment, but further exploration in larger clinical trials is needed.

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