Presence of Chronic Obstructive Pulmonary Disease (COPD) Impair Survival in Lung Cancer Patients Receiving Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI): A Nationwide, Population-Based Cohort Study

Wu, Chiung-Jen; Rau, Kun‐Ming; Lee, Wei‐Chieh; Hsieh, Meng‐Che; Liu, Jia‐Sin; Chen, Yen‐Yang; Su, Yu-Li

doi:10.3390/jcm8071024

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…This result is consistent with the results of the prior large-scale clinical study. 10 However, that study did not describe more genetic information. Previous literatures have reported that TP53 is an unfavorable factor for the prognosis and targeted therapy of lung cancer.…”

Section: Discussionmentioning

confidence: 94%

“…A retrospective study based on the National Health Insurance Research Database in Taiwan indicated lung cancer patients with EGFR-TKI treatment had a worse survival outcome if patients had pre-existing COPD. 10 However, the patients in this study lacked further description of genetic mutations. Another retrospective immunotherapy research investigated the clinical impact of COPD on the treatment response to palliative pembrolizumab in non-small cell lung cancer (NSCLC).…”

Section: Introductionmentioning

confidence: 92%

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Molecular and Clinicopathological Characteristics of Lung Cancer Concomitant Chronic Obstructive Pulmonary Disease (COPD)

Ma¹,

Zhang²,

Zhao³

et al. 2022

COPD

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Introduction Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, but its pathophysiology and genomics features are still unclear. Methods In this study, we retrospectively collected lung cancer concomitant COPD (COPD-LC) and non-COPD lung cancer (non-COPD-LC) patients, who performed next generation sequencing (NGS) and had clinicopathological information simultaneously. The COPD-LC data from the TCGA cohort were collected to conduct further analysis. Results A total of 51 COPD-LC patients and 88 non-COPD-LC patients were included in the study. Clinicopathological analysis showed that proportion of male gender, older age, and smoking patients were all substantially higher in COPD-LC group than in non-COPD-LC group (all P<0.01). Comparing the genomic data of the two groups in our cohort, COPD-LC had higher mutation frequency of LRP1B (43% vs 9%, P = 0.001), EPHA5 (24% vs 1%, P = 0.002), PRKDC (14% vs 1%, P = 0.039), PREX2 (14% vs 0%, P = 0.012), and FAT1 (14% vs 0%, P = 0.012), which had a relationship with improved tumor immunity. Immunotherapy biomarker of PD-L1 positive expression (62.5% vs 52.0%, P = 0.397) and tumor mutation burden (TMB, median TMB: 7.09 vs 2.94, P = 0.004) also were higher in COPD-LC. In addition, RNA data from TCGA further indicated tumor immunity increased in COPD-LC. Whereas, COPD-LC had lower frequency of EGFR mutation (19% vs 50%, P = 0.013) and EGFR mutant COPD-LC treated with EGFR-TKI had worse progression-free survival (PFS) (HR = 3.52, 95% CI: 1.27–9.80, P = 0.01). Conclusion In this retrospective study, we first explored molecular features of COPD-LC in a Chinese population. Although COPD-LC had lower EGFR mutant frequency and worse PFS with target treatment, high PD-L1 expression and TMB indicated these patients may benefit from immunotherapy.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 92%

Molecular and Clinicopathological Characteristics of Lung Cancer Concomitant Chronic Obstructive Pulmonary Disease (COPD)

Ma¹,

Zhang²,

Zhao³

et al. 2022

COPD

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COPD: the risk of cancer and the impact on cancer care

Yang¹,

Shaw²,

Stephens³

et al. 2022

Lung Diseases and Cancer

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Establishment and genetically characterization of patient-derived xenograft models of cervical cancer

Zou

Zhang

et al. 2022

BMC Med Genomics

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Purpose Patient-derived xenograft (PDX) models were established to reproduce the clinical situation of original cancers and have increasingly been applied to preclinical cancer research. Our study was designed to establish and genetically characterize cervical cancer PDX models. Methods A total of 91 fresh fragments obtained from 22 surgically resected cervical cancer tissues were subcutaneously engrafted into female NOD-SCID mice. Hematoxylin and eosin (H&E) staining was performed to assess whether the established PDX models conserved the histological features of original patient cervical cancer tissues. Moreover, a Venn diagram was applied to display the overlap of all mutations detected in whole-genome sequencing (WGS) data from patient original cervical cancer (F0) and F2-, F3-PDX models. The whole exome sequencing (WES) and the “maftools” package were applied to determine the somatic mutations among primary cervical cancers and the established PDX models. Results Our study successfully developed a panel of cervical cancer PDX models and the latency time of cervical cancer PDX model establishment was variable with a progressive decrease as the passage number increased, with a mean time to initial growth of 94.71 days in F1 engraftment to 40.65 days in F3 engraftment. Moreover, the cervical cancer PDX models preserved the histological features of their original cervical cancer. WGS revealed that the genome of original cervical cancer was preserved with high fidelity in cervical cancer PDX models throughout the xenografting and passaging process. Furthermore, WES demonstrated that the cervical cancer PDX models maintained the majority somatic mutations of original cervical cancer, of which the KMT2D, LRP1B, NAV3, TP53, FAT1, MKI67 and PKHD1L1 genes were identified as the most frequently mutated genes. Conclusions The cervical cancer PDX models preserved the histologic and genetic characteristics of their original cervical cancer, which helped to gain a deeper insight into the genetic alterations and lay a foundation for further investigation of the molecular targeted therapy of cervical cancer.

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Presence of Chronic Obstructive Pulmonary Disease (COPD) Impair Survival in Lung Cancer Patients Receiving Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI): A Nationwide, Population-Based Cohort Study

Cited by 4 publications

References 36 publications

Molecular and Clinicopathological Characteristics of Lung Cancer Concomitant Chronic Obstructive Pulmonary Disease (COPD)

Molecular and Clinicopathological Characteristics of Lung Cancer Concomitant Chronic Obstructive Pulmonary Disease (COPD)

COPD: the risk of cancer and the impact on cancer care

Establishment and genetically characterization of patient-derived xenograft models of cervical cancer

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