Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer

Chen, Mao; Yuan, Jinqiu; Yang, Zu‐Yao; Fu, Xiaohong; Wu, Xinyin; Tang, Jin‐Ling

doi:10.1097/md.0000000000000775

Cited by 61 publications

(55 citation statements)

References 47 publications

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“…Recent reports suggested that presence of mEGFR ctDNA is associated with longer PFS and OS in advanced NSCLC patients treated with EGFR‐TKIs . In this study, poor PFS and a trend toward shorter OS times were observed in lung adenocarcinoma patients with plasma mEGFR ctDNAs.…”

Section: Discussionsupporting

confidence: 52%

“…Recent reports suggested that presence of mEGFR ctDNA is associated with longer PFS and OS in advanced NSCLC patients treated with EGFR-TKIs. 23,24 In this study, poor PFS and a trend toward shorter OS times were observed in lung adenocarcinoma patients with plasma mEGFR ctDNAs. In addition, this analysis also showed that EGFR mutations in ctDNA were associated with shorter duration of disease control in advanced lung adenocarcinoma patients treated with EGFR-TKIs.…”

Section: Discussionmentioning

confidence: 58%

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Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma

Kim

Lee

et al. 2019

Thoracic Cancer

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BackgroundCirculating tumor DNA (ctDNA) is a biomarker for the selection of target agents in various malignancies. In this study, we examined the effect of ctDNA presence on the response to EGFR‐tyrosine kinase inhibitor (TKI) and on the prognosis in lung adenocarcinoma.MethodsctDNA of EGFR‐TKI sensitizing mutations (mEGFR), L858R substitution and Exon 19 deletion (E19d) mutation, was evaluated using droplet digital PCR (ddPCR) in 81 patients with lung adenocarcinoma which harbored mEGFR in the corresponding tumor tissues.ResultsThe study recruited lung cancer patients at various stages, and the sensitivity, specificity, and area under the curve (AUC) of mEGFR ctDNA detection by ddPCR were 40.0%, 88.5%, and 0.68, respectively. It showed higher sensitivity (75.0% vs. 10.0%) and AUC (0.83 vs. 0.49) in the advanced stages of lung adenocarcinoma compared with the early stages and the number of metastases and the fractional abundance of mEGFR ctDNA showed a strong correlation (σ = 0.516; P < 0.001, Spearman correlation test). There was a significantly shorter progression‐free survival and duration of disease control by EGFR‐TKIs in the ctDNA‐positive group than the negative group (14.0 vs. 41.0 months, P = 0.02 and 12.0 vs. 23.0 months, P = 0.02, log‐rank test, respectively). There was a trend for overall survival time to be shorter in patients with mEGFR ctDNA than for patients without mEGFR ctDNA (35.6 vs. 67.1 months, P = 0.06, log‐rank test).ConclusionsThese data showed that mEGFR ctDNA detection using ddPCR is useful in the advanced stages and its presence predicted distant metastasis and poor clinical outcome in lung adenocarcinoma.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 58%

Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma

Kim

Lee

et al. 2019

Thoracic Cancer

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“…Although no significant differences were observed in both ORR (P=0.489) and DCR (P=0.548) between the T+P+ and T+P-groups, the T+P+ group showed a considerably better ORR than the T+P-group (44.1% versus 30.0%). This is consistent with a previous study, reporting that patients with both tumor tissue and plasma EGFR activating mutations showed superior progressionfree survival (PFS) and overall survival (OS) compared to patients with tumor tissue mutations only [10,20]. Also, it has been reported that the sensitivity of plasma-based genotyping was associated with tumor burden [8].…”

Section: Discussionsupporting

confidence: 92%

A Comparison of Arms‐plus and Droplet Digital PCR for Detecting Egfr Activating Mutations in Plasma

2017

Respirology

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1Background and Aim: Galectin-3, a β-galactoside-binding lectin, has been shown to be involved in tumor development. However the significance of galectin-3 expression in lung cancer remains unclear. Recently, several studies demonstrated that galectin-3 is upregulated by hypoxiainducible factor 1α (HIF-1α) in several types of cancers other than lung cancer. We hypothesized that hypoxia would promote tumor progression via upregulation of galectin-3 in lung cancer. The aim of this study is to evaluate the biological role of galectin-3 in human lung adenocarcinoma and clarify its prognostic significance in patients.Methods: (1) Galectin-3 or scrambled shRNA were transfected into human lung adenocarcinoma cell line, A549 to evaluate the effect of hypoxia in vitro. Cell migration and invasion assays were performed under hypoxia. To study RhoA activation, pull-down assay was done to assess the GTP-bound RhoA. (2) Galectin-3 expression was analyzed by immunohistochemistry in 57 patients with stag I lung adenocarcinoma who underwent surgical resection.Results: (1) Hypoxia induced the upregulation of HIF-1α and galectin-3, and increased cell migration and invasion. Silence of galectin-3 expression in A549 significantly decreased cell migration and invasion in hypoxic condition. Activation of RhoA was significantly decreased in galectin-3 knockdown cells compared with control cells. (2) Galectin-3 expression was observed in 20 patients (35.1%), and significantly associated with the incidence of recurrences (p<0.001) and the relapse-free survival time (p=0.001).Conclusion: These data suggest that galecin-3 would contribute to tumor invasion in hypoxia through RhoA activation and indicate that galectin-3 expression on tumor cells would serve as a prognostic marker in lung adenocarcinoma. Therefore, galectin-3 could be a potential therapeutic target in human lung adenocarcinoma. Background and Aim: Low-dose computed tomography for lung screening is able to identify smaller nodules more often than can chest radiographs. However, complications of invasive diagnostic procedures of detected nodules are common in practice. Exosomes, membrane vesicles released from cells, contain a diverse array of biomolecules that closely reflect the biologic state of cell and tissue from which they are released. The aim of this study is to investigate diagnostic values in bronchoalveolar lavage (BAL) fluid exosomal micro (mi)RNA in early stage lung adenocarcinoma.Methods: We chose candidate miRNAs known as having a diagnostic value of lung adenocarcinoma. Exosomes were isolated from BAL fluid from control subjects (n = 15) and patients with lung adenocarcinoma (n = 13). Exosomal RNA was analyzed by using commercial kit containing probes for selected 6 miRNAs. Results were validated with quantitative RT-PCR.Results: The presence of miRNAs was confirmed in exosomes from BAL fluid of both lung adenocarcinoma patients and control subjects.MiR-126 (p<0.001) and were present in significantly higher levels in the BAL fluid of lung adenocarcinoma pat...

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“…Additional studies evaluating the concordance of plasma/serum and tissue EGFR mutations (Table 2) have reported a wide range of concordance rates (27.5%-100%) and sensitivities (17.1%-100%), with consistently high specificities (71.4%-100%). The disparities in sensitivities are heavily technology-dependent.Two recent meta-analyses assessing the diagnostic accuracy of cfDNA EGFR mutations demonstrated a pooled sensitivity of 61% and 67.4% and specificity of 90% and 93.5%, respectively [15,16]. Genetic interrogation of cfDNA via NGS has revealed additional mutations beyond EGFR.…”

Section: Cfdnamentioning

confidence: 99%

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Levy

Cordova

et al. 2016

The Oncologist

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A firmer understanding of the genomic landscape of lung cancer has recently led to targeted, therapeutic advances in non-small cell lung cancer. Historically, the reference standard for the diagnosis and genetic interrogation for advanced-stage patients has been tissue acquisition via computed tomography-guided core or fine needle aspiration biopsy. However, this process can frequently put the patient at risk and remains complicated by sample availability and tumor heterogeneity. In addition, the time required to complete the diagnostic assays can negatively affect clinical care. Technological advances in recent years have led to the development of blood-based diagnostics or “liquid biopsies” with great potential to quickly diagnose and genotype lung cancer using a minimally invasive technique. Recent studies have suggested that molecular alterations identified in cell-free DNA (cfDNA) or circulating tumor DNA can serve as an accurate molecular proxy of tumor biology and reliably predict the response to tyrosine kinase therapy. In addition, several trials have demonstrated the high accuracy of microRNA (miRNA) platforms in discerning cancerous versus benign nodules in high-risk, screened patients. Despite the promise of these platforms, issues remain, including varying sensitivities and specificities between competing platforms and a lack of standardization of techniques and downstream processing. In the present report, the clinical applications of liquid biopsy technologies, including circulating tumor cells, proteomics, miRNA, and cfDNA for NSCLC, are reviewed and insight is provided into the diagnostic and therapeutic implications and challenges of these platforms.

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Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 61 publications

References 47 publications

Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma

Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma

A Comparison of Arms‐plus and Droplet Digital PCR for Detecting Egfr Activating Mutations in Plasma

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

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