scholarly journals Copy‐number variation of MCL1 predicts overall survival of non‐small‐cell lung cancer in a Southern Chinese population

2016 ◽  
Vol 5 (9) ◽  
pp. 2171-2179 ◽  
Author(s):  
Jieyun Yin ◽  
Yangkai Li ◽  
Hao Zhao ◽  
Qin Qin ◽  
Xiaorong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Copy Number Variation ◽  
Small Cell Lung Cancer ◽  
Copy Number ◽  
Chinese Population ◽  
Small Cell ◽  
Small Cell Lung ◽  
Southern Chinese ◽  
Number Variation

scholarly journals Prognostic Value of Germline Copy Number Variants and Environmental Exposures in Non-small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Shizhen Chen ◽  
Liming Lu ◽  
Jianfeng Xian ◽  
Changhong Shi ◽  
Jinbin Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Chinese Population ◽  
Validation Cohort ◽  
Small Cell ◽  
Polygenic Risk Score ◽  
Small Cell Lung ◽  
Training Cohort

Germline copy number variant (gCNV) has been studied as a genetic determinant for prognosis of several types of cancer, but little is known about how it affects non-small cell lung cancer (NSCLC) prognosis. We aimed to develop a prognostic nomogram for NSCLC based on gCNVs. Promising gCNVs that are associated with overall survival (OS) of NSCLC were sorted by analyzing the TCGA data and were validated in a small Chinese population. Then the successfully verified gCNVs were determined in a training cohort (n = 570) to develop a prognostic nomogram, and in a validation cohort (n = 465) to validate the nomogram. Thirty-five OS-related gCNVs were sorted and were reduced to 15 predictors by the Lasso regression analysis. Of them, only CNVR395.1 and CNVR2239.1 were confirmed to be associated with OS of NSCLC in the Chinese population. High polygenic risk score (PRS), which was calculated by the hazard effects of CNVR395.1 and CNVR2239.1, exerted a significantly higher death rate in the training cohort (HR = 1.41, 95%CI: 1.16–1.74) and validation cohort (HR = 1.42, 95%CI: 1.13–1.77) than low PRS. The nomogram incorporating PRS and surrounding factors, achieved admissible concordance indexes of 0.678 (95%CI: 0.664–0.693) and 0.686 (95%CI: 0.670–0.702) in predicting OS in the training and validation cohorts, respectively, and had well-fitted calibration curves. Moreover, an interaction between PRS and asbestos exposure was observed on affecting OS (Pinteraction = 0.042). Our analysis developed a nomogram that achieved an admissible prediction of NSCLC survival, which would be beneficial to the personalized intervention of NSCLC.

scholarly journals MET Gene Copy Number Predicts Worse Overall Survival in Patients with Non-Small Cell Lung Cancer (NSCLC); A Systematic Review and Meta-Analysis

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107677 ◽  
Author(s):  
Anastasios Dimou ◽  
Lemuel Non ◽  
Young Kwang Chae ◽  
William J. Tester ◽  
Konstantinos N. Syrigos
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Copy Number ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung

scholarly journals Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 107 ◽  
Author(s):  
Wen Li ◽  
Ming Jia ◽  
Jian Wang ◽  
Jie Lu ◽  
Jing Deng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Serum Level ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Chinese Population ◽  
Serum Levels ◽  
Small Cell ◽  
Snp Analysis ◽  
Small Cell Lung ◽  
Southern Chinese

Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. Methods: This case–control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. Results: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29–0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33–0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75–1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51–1.14). Conclusions: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer.

scholarly journals Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marianne Oulhen ◽  
Patrycja Pawlikowska ◽  
Tala Tayoun ◽  
Marianna Garonzi ◽  
Genny Buson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Epithelial To Mesenchymal Transition ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Anaplastic Lymphoma

AbstractGatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer. Single CTC isolation and phenotyping were performed by DEPArray or fluorescence-activated cell sorting following enrichment and immunofluorescence staining (ALK/cytokeratins/CD45/Hoechst). CNA heterogeneity was evaluated in six ALK-rearranged patients harboring ≥ 10 CTCs/20 mL blood at resistance to 1st and 3rd ALK-TKIs and one presented gatekeeper mutations. Out of 82 CTCs isolated by FACS, 30 (37%) were ALK+/cytokeratins-, 46 (56%) ALK-/cytokeratins+ and 4 (5%) ALK+/cytokeratins+. Sequencing of 43 CTCs showed highly altered CNA profiles and high levels of chromosomal instability (CIN). Half of CTCs displayed a ploidy >2n and 32% experienced whole-genome doubling. Hierarchical clustering showed significant intra-patient and wide inter-patient CTC diversity. Classification of 121 oncogenic drivers revealed the predominant activation of cell cycle and DNA repair pathways and of RTK/RAS and PI3K to a lower frequency. CTCs showed wide CNA heterogeneity and elevated CIN at resistance to ALK-TKIs. The emergence of epithelial ALK-negative CTCs may drive resistance through activation of bypass signaling pathways, while ALK-rearranged CTCs showed epithelial-to-mesenchymal transition characteristics potentially contributing to ALK-TKI resistance. Comprehensive analysis of CTCs could be of great help to clinicians for precision medicine and resistance to ALK-targeted therapies.

scholarly journals Impact of neutrophil-to-lymphocyte ratio throughout the course of chemoradiotherapy on overall survival and distant failure in unresectable stage III non-small cell lung cancer

2021 ◽  
Author(s):  
Hiromitsu Kanzaki ◽  
Yasushi Hamamoto ◽  
Kei Nagasaki ◽  
Toshiyuki Kozuki
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Related Factors ◽  
Distant Failure ◽  
Unresectable Stage ◽  
Significant Factors

Abstract Purpose Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with treatment outcomes in various cancers; however, the optimal timing to measure NLR is unclear. In this study, “average-NLR” was newly devised, which reflects the NLR throughout the course of radiotherapy, and its usefulness was assessed for stage III non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Materials and methods A total of 111 patients who received definitive chemoradiotherapy for unresectable stage III NSCLC were reviewed. Patient/tumor-related factors, treatment-related, and NLR-related factors (average-NLR, pre- and post-radiotherapy NLR, NLR-nadir, NLR-maximum) were assessed using univariate and multivariate analyses. Results The median follow-up period was 43.8 months among the survivors. In the multivariate analysis, average-NLR and post-radiotherapy NLR were significant factors for the overall survival (OS) (p = 0.016 and 0.028) and distant failure (DF) (p = 0.008 and 0.040). For the patients with low, intermediate, and high average-NLR, the median OS was 41.2, 37.7, and 14.8 months, respectively, and the median DF free time was 52.5, 13.5, and 8.9 months, respectively. Conclusion Average-NLR and post-radiotherapy NLR were significant factors for the OS and DF. Average-NLR, which was available immediately after the completion of chemoradiotherapy, seemed to be helpful for treatment decisions.

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