CYP1A1*2A polymorphism as a prognostic factor for the advanced lung cancer patients treated with EGFR-TKI and its correlation with EGFR mutation.

e20519 Background: The frequency of EGFR mutation in Asian advanced lung cancer patients is about 40% and the application of EGFR tyrosine kinase inhibitors (TKIs) has become a standard treatment therapy. Several studies showed that usage of EGFR TKIs in adjuvant or neo-adjuvant therapy was promising, while the mutation profile of EGFR mutations in resectable Chinese lung cancer patients was still scanty. Our study investigated EGFR mutation profile and its correlation with clinicopathological factors. Methods: 343 resectable patients with lung cancer were selected for eligibility criteria, and tumor tissues were collected for gene detection. EGFR genetic testing was performed by amplification refractory mutation system PCR (ARMS-PCR) with specific sensitive mutation sites. The clinicopathological factors of study population were recorded based on pre-design protocol. Chi-square or fish exact test were used to statistic analysis Results: A total of 343 patients were enrolled in study. 42.6% (146/343) patients were male, 20.4% (68/333) patients were smokers, the adenocarcinoma accounted for 93.8 % (319/340), and stage 0, I, II, III was 7.3% (25/343), 68.8% (236/343), 8.5% (29/343), 15.5% (53/343), respectively. The frequency of EGFR mutation was 54.2% (186/343) in whole population, and the proportion of EGFR L858R, 19Del, 719X, 768I, 861Q mutation was 31.2% (107/343), 21.3% (73/343), 1.2% (4/343), 1.0% (3/343), 1.0% (3/343), respectively. 1.2% (4/343) patients presented EGFR co-mutation (EGFR G719X/S768I; L858R/S768I; G719X/S768I; L858R/L861Q) .The mutation frequency of EGFR mutation was associated with sex, smoking, differentiation, pathology (P = 0.0076, < 0.0001, < 0.0001, < 0.0001, respectively). In subgroup analysis, the incidence of two main mutation types, EGFR L858R and 19del, were associated with disease stage (P = 0.044) and age (P = 0.035). Conclusions: EGFR mutation in resectable lung cancer was a common phenomenon as advanced stage and our study might provide useful informations for using EGFR-TKIs in further adjuvant or neo-adjuvant therapy.

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Analytical Validation of a Pan-Cancer Panel for Cell-Free Assay for the Detection of EGFR Mutations

Diagnostics ◽

10.3390/diagnostics11061022 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1022

Author(s):

Min-Kyung So ◽

Jong-Ho Park ◽

Jong-Won Kim ◽

Ja-Hyun Jang

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Cancer Cell ◽

Reference Materials ◽

Egfr Mutation ◽

Egfr Mutations ◽

Advanced Lung Cancer ◽

Clinical Samples ◽

Lung Cancer Patients ◽

Pan Cancer

Liquid biopsies have increasingly shown clinical utility. Although next-generation sequencing has been widely used for the detection of somatic mutations from plasma, performance characteristics vary by platform. Therefore, thorough validation is mandatory for clinical use. This study aimed to evaluate the analytical validity of the Oncomine Pan-Cancer Cell-Free Assay. A massively parallel sequencing for the assay was performed using the Ion S5 XL System with Ion 540 kit. The analytical sensitivity and precision were evaluated using pre-characterized reference materials. The specificity was evaluated using plasma from healthy subjects. A comparison with the Cobas EGFR Mutation Test v2 was performed using reference materials and plasma from lung cancer patients. For SNVs and short indels, the analytical sensitivities at variant allele frequencies (VAFs) of 0.1%, 0.5%, and 1% were 50%, 93.4%, and 100% with 20 ng of input, respectively. The overall precision of the true positive variants was 98% at a VAF of 1% with 20 ng input. The assay showed a similar sensitivity to that of the Cobas EGFR Mutation Test v2 at a VAF of 0.5% with 20 ng of input and 100% concordance on clinical samples. The Pan-Cancer Cell-Free Assay can be applied to detect EGFR mutations in advanced lung cancer patients, although follow-up studies will be needed to evaluate the analytical validity for other types of genes and aberrations using clinical samples.

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The landscape of tumor mutational burden and its clinical significance in patients with lung cancer: a Multi-omics study with a meta-analysis

10.21203/rs.3.rs-31920/v1 ◽

2020 ◽

Author(s):

Ying Wang ◽

Linhai Zhu ◽

Pinghui Xia ◽

Zhitian Wang ◽

Li Yu ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Lung Adenocarcinoma ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients

Abstract Background: Current research on tumor mutational burden (TMB) has focused on tumor immunotherapy responsiveness, but the role of TMB in non-immunotherapy patients is unclear. The purpose of this study is to explore the effect of TMB on lung cancer patients in order to clarify and expand the clinical significance of TMB in lung cancer.Methods: We download mutation data of lung cancer cases from The Cancer Genome Atlas (TCGA) database to analyze TMB and its composition, and study the relationship between TMB and clinicopathological characteristics of lung cancer patients. We then systematically retrieved and analyzed studies on the relationship between TMB and survival outcomes. The hazard ratio (HR) and its 95% confidence interval (CI) were used as an effective size to assess the survival outcomes. The subgroup analyses based on the pathological type, treatment method, TMB detection method and detection materials were also performed to explore the factors that might affect the interpretation of TMB results.Results: TMB in lung squamous cell carcinoma is lower than those in lung adenocarcinoma. In lung adenocarcinoma, patients with EGFR mutation have lower TMB than patients with EGFR wild-type. The summary analysis found that TMB is a better prognostic factor in small cell lung cancer, and more evident in small cell lung cancer receiving immunotherapy. TMB is a neutral or poor prognostic indicator in non-small cell lung cancer, but a better prognostic factor in non-small cell lung cancer receiving immunotherapy. In patients with lung adenocarcinoma, including those with EGFR mutation and receiving EGFR-targeted therapies, high TMB means worse survival. TMB detected by blood specimens is inconsistent and unstable compared to TMB detected by tissue. The clinical significance of TMB from blood specimens needs further study on extensive sample data.Conclusions: The pooled results indicated that TMB is a good prognostic factor in lung cancer patients receiving immunotherapy. But high TMB is connected with worse survival in non-small cell lung cancer without receiving immunotherapy, especially in lung adenocarcinoma. For lung adenocarcinoma patients with both EGFR mutation and high TMB, how to make a choice between EGFR-targeted therapy and immunotherapy is still a problem that requires further research.

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Best Response According to RECIST During First-line EGFR-TKI Treatment Predicts Survival in EGFR Mutation-positive Non–Small-cell Lung Cancer Patients

Clinical Lung Cancer ◽

10.1016/j.cllc.2018.01.005 ◽

2018 ◽

Vol 19 (3) ◽

pp. e361-e372 ◽

Cited By ~ 7

Author(s):

Ting-Hui Wu ◽

Emily Han-Chung Hsiue ◽

Jih-Hsiang Lee ◽

Chia-Chi Lin ◽

Wei-Yu Liao ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Lung Cancer Patients ◽

Best Response ◽

Tki Treatment ◽

Egfr Tki

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Immune checkpoint inhibitors combined with chemotherapy/antiangiogenic therapy for heavily treated advanced lung cancer patients with EGFR mutation: a retrospective analysis

10.22541/au.160071096.65686217 ◽

2020 ◽

Author(s):

Ran Hu ◽

Zhiting Zhao ◽

Yue Shi ◽

Meiqi Shi ◽

Guohao Xia ◽

...

Keyword(s):

Lung Cancer ◽

Retrospective Analysis ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Egfr Mutation ◽

Checkpoint Inhibitors ◽

Antiangiogenic Therapy ◽

Advanced Lung Cancer ◽

Lung Cancer Patients

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NF-κB–driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1522612113 ◽

2016 ◽

Vol 113 (18) ◽

pp. E2526-E2535 ◽

Cited By ~ 36

Author(s):

Ching-Feng Chiu ◽

Yi-Wen Chang ◽

Kuang-Tai Kuo ◽

Yu-Shiuan Shen ◽

Chien-Ying Liu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Egfr Mutation ◽

Lung Cancer Cells ◽

Cancer Stemness ◽

Lung Cancer Patients ◽

Gefitinib Resistance ◽

Egfr Tki ◽

Egfr Tkis

Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib or erlotinib) significantly prolongs survival time for patients with tumors harboring an activated mutation on EGFR; however, up to 40% of lung cancer patients exhibit acquired resistance to EGFR-TKIs with an unknown mechanism. FOXO3a, a transcription factor of the forkhead family, triggers apoptosis, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we observed that a high level of FOXO3a was correlated with EGFR mutation-independent EGFR-TKI sensitivity, the suppression of cancer stemness, and better progression-free survival in lung cancer patients. The suppression of FOXO3a obviously increased gefitinib resistance and enhanced the stem-like properties of lung cancer cells; consistent overexpression of FOXO3a in gefitinib-resistant lung cancer cells reduced these effects. Moreover, we identified that miR-155 targeted the 3′UTR of FOXO3a and was transcriptionally regulated by NF-κB, leading to repressed FOXO3a expression and increased gefitinib resistance, as well as enhanced cancer stemness of lung cancer in vitro and in vivo. Our findings indicate that FOXO3a is a significant factor in EGFR mutation-independent gefitinib resistance and the stemness of lung cancer, and suggest that targeting the NF-κB/miR-155/FOXO3a pathway has potential therapeutic value in lung cancer with the acquisition of resistance to EGFR-TKIs.

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