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Tangfeng Lv
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P16 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Translational) (ID 155)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P16.05 - Exploratory Study of Sintilimab Intrapleural Therapy for NSCLC-Mediated Malignant Pleural Effusion (ID 1478)
00:00 - 00:00 | Presenting Author(s): Tangfeng Lv
- Abstract
Introduction
NSCLC-mediated malignant pleural effusion (MPE) severely restricts the quality of life and renders a poor prognosis, and intrapleural therapy plays an important part in the treatment. Our previous studies have revealed that tumor-derived exosomes highly express PD-L1 and play a role in immune-escape and promoting MPE formation, therefore injecting anti-PD-1 locally may bring clinical benefits. In our pre-clinical MPE model, mice were responsive to anti-PD-1 treatments, resulting in reduced volume of MPE. Compared to nivolumab and pembrolizumab, sintilimab functions more efficiently in boosting the immune response against cancer cells, as assessed by the increased CD8+ cells and CD8+ /Treg ratio. Based on these preliminary findings, we conducted the first single-arm phase I study to investigate the efficacy and safety of sintilimab intrapleural therapy for patients with NSCLC‐mediated MPE.
Methods
Eligible patients had histologically or cytologically confirmed NSCLC with moderate to large malignant pleural effusion and required local interventions. Patients who were receiving anti-angiogenesis or any other targeted therapies were excluded. Prior to the intrapleural injection, all the participants should receive catheter drainage of pleural effusion and achieve radiographically confirmed sufficient drainage, and the volume of pleural fluid should be less than 100 ml/day for two consecutive days. In addition to systemic chemotherapy, participants were administrated by single dose sintilimab (100mg) intrapleural on the same day of the last drainage. Follow-up radiography was performed at 5- and 10-weeks post-treatment to assess the local control of MPE. The primary endpoint was pleurodesis success rate at 5-weeks, and the secondary endpoints include pleurodesis success rate at 10-weeks, objective response, and safety of intrapleural injection. Pleurodesis success was defined as fluid re-occupying < 25% in hemithorax.
Results
Between May 2019 and Jan 2020, five male patients and two female patients were enrolled. Of the five patients who completed the 5-weeks assessment, four patients (80%) had successful pleurodesis while one failed. As of data cut-off, four patients (66.7%) completed the 10-weeks assessment and had successful pleurodesis. Furthermore, all seven patients achieved stable disease, regardless of the chemotherapy they were receiving or had received (five patients were receiving first-line pemetrexed plus platinum doublet, and one was enrolled after second-line failure). 5/7 patients experienced treatment emerged adverse events (TEAEs) within 30 days after intrapleural therapy, which were considered to be associated with systemic chemotherapy only. No immune-related adverse events were reported. Neither chest infection nor pneumonia was reported. The patient who failed the 5-weeks assessment experienced serious AE (SAE), presenting with chest tightness and shortness of breath on day two after treatment. The above SAE was resolved after pleural effusion drainage, anti-infective prophylaxis, and symptomatic treatment.
Conclusion
This exploratory study is the first to evaluate the intrapleural use of anti-PD-1 in NSCLC-mediated MPE. Preliminary data showed that intrapleural injection of sintilimab is effective and safe. Enrolment is on-going, and more data will be analysed to define its clinical application in NSCLC-mediated MPE.
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P36 - Pathology - Prognosis (ID 106)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P36.08 - Effect of Soluble CD39 and PD-L1 Levels on Diagnosis and Prognosis of Lung Cancer Patients with Malignant Pleural Effusion (ID 2145)
00:00 - 00:00 | Presenting Author(s): Tangfeng Lv
- Abstract
Introduction
Immune-related soluble molecules, including some checkpoint inhibitors, have attracted extensive attention from researchers. Studies have confirmed that soluble PD-L1 was associated with the prognosis of malignant tumors. CD39, which participates in the decomposition of ATP into adenosine, also plays a role in promoting tumor immune escape. However, few studies mentioned soluble CD39. We explored the significance of these two soluble molecules in tumor immunity.
Methods
We collected plasma samples from 90 lung adenocarcinoma patients diagnosed in our hospital, and some pleural effusion samples from patients with malignant pleural effusion. The levels of sCD39 and sPD-L1 in different specimens were determined by ELISA, and their correlation with clinicopathological characteristics was explored. We also followed up the patients included in the study, counted their survival status, and observed the effect of two soluble molecules on the prognosis of patients with advanced lung cancer.
Results
We confirmed that plasma levels of sPD-L1 and sCD39 in lung adenocarcinoma patients were higher than those in healthy controls. Older patients (>60 years old) had higher levels of sPD-L1 (p=0.007). Among lung cancer patients with EGFR mutation, the lowest level of sPD-L1 was found in patients with exon 19 deletion (p= 0.018). Platelet counts and distant organ metastases can also affect plasma sPD-L1 levels in patients. In subgroup analysis, the levels of sPD-L1 were higher in female, non-smoking and elderly patients with lung adenocarcinoma. sCD39 was significantly elevated in patients with higher white blood cell counts, platelet counts, and neutrophil to lymphocyte ratio (NLR) (p < 0.05). In patients with positive EGFR mutation, sCD39 was correlated with lymph node metastasis, CEA, WBC and PLT. For advanced lung cancer patients with pleural effusion, there was a significant correlation between plasma sPD-L1 and sCD39 (p=0.013). The levels of sCD39 in pleural effusion and plasma of matched patients were also positively correlated. COX multivariate survival regression analysis showed that patients with high plasma sPD-L1 level had poor prognosis (p= 0.013). Patients with lower expression of sCD39 in plasma had longer survival time (p = 0.053).
Conclusion
Soluble PD-L1 and soluble CD39 in plasma of lung cancer patients were closely related to various clinicopathological features. Women, non-smokers, and elderly lung adenocarcinoma patients had higher levels of sPD-L1. Maybe soluble CD39 could replace the commonly used clinical indicators and reflect the immune status of the patient's body. Patients with high sPD-L1 and high sCD39 levels often had a poor prognosis. These two immune-related molecules can be used as biomarkers for the diagnosis and prognosis of advanced lung cancer.
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P53 - Tumor Biology and Systems Biology - Basic and Translational Science - Misc. Topics (ID 213)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P53.07 - Clinicopathologic Characteristics of Patients With PTPN11 Mutations in East Asian Non-Small Cell Lung Cancer Patients (ID 678)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
The PTPN11 (protein tyrosine-phosphatase non-receptor type-11) gene encodes SHP2, which is a member of ubiquitously expressed protein tyrosine phosphatase with positive regulatory roles in signalling pathways, including Ras-mitogenactivated protein kinase signaling. Somatic mutations in PTPN11 are common in histiocytic sarcoma(HS), juvenile myelomonocytic leukemia (JMML) and acute myeloid leukemia (AML), that responded to the MAPK extracellular signal-regulated kinase (MEK)-inhibitor trametinib. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring PTPN11 mutations.
Methods
A total of 724 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of PTPN11 mutations and other genes were detected by next generation sequencing.
Results
PTPN11 gene mutation rate was 0.69% (5/724) in non-small cell lung cancer, including D425N (1 patient), D425Y (1 patient), R527C (1 patient), E76Q (1 patient) and V382I (1 patient), and median overall survival (OS) for these patients was 17.0 months. Among them, all patients were PTPN11 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=2) co-occurring TP53 mutations had a median OS of 17.0 months and 10.5 months respectively (P=0.64); patients with (n=4) or without (n=1) co-occurring KRAS mutations had a median OS of 17.0 months and 4.0 months respectively (P=0.35); patients with (n=2) or without (n=3) co-occurring ATM mutations had a median OS of 10.5 months and 17.0 months respectively (P=0.64); patients with (n=2) or without (n=3) co-occurring EPHA3 mutations had a median OS of 17.0 months and 4.0 months respectively (P=0.20).
Conclusion
Our data reveal PTPN11 genetic alter occurs in a subset of NSCLC. NGS might be useful for evaluation of PTPN11 unclassified variants. Our results show that PTPN11 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through trametinib might offer new opportunities.
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P55 - Tumor Biology and Systems Biology - Basic and Translational Science - Cell Cycle (ID 192)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P55.01 - Different Types of CDK4 Mutations in East Asian Non-Small Cell Lung Cancer Patients (ID 688)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, has an especially crucial role in tumorigenesis. This region harbors another important partner in the RB1-CCND1 pathway, namely, cyclin dependent kinase 4 (CDK4). The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring CDK4 mutations.
Methods
A total of 1049 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of CDK4 mutations and other genes were detected by next generation sequencing.
Results
CDK4 gene mutation rate was 0.67% (7/1049) in non-small cell lung cancer, including G13C (1 patient), D119V (1 patient), D236Y (1 patient), K282R (1 patient), K155N (1 patient), R38K (1 patient) and E7Q (1 patient), and median overall survival (OS) for these patients was 23.0 months. Among them, all patients were CDK4 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=3) co-occurring EGFR mutations had a median OS of 14.5 months and 23.0 months respectively (P=0.43); patients with (n=5) or without (n=2) co-occurring TP53 mutations had a median OS of 23.0 months and 14.5 months respectively (P=0.81); patients with (n=2) or without (n=5) co-occurring KRAS mutations had a median OS of 14.5 months and 23.0 months respectively (P=0.81); patients with (n=2) or without (n=5) co-occurring ALK mutations had a median OS of 6.0 months and 23.0 months respectively (P=0.01).
Conclusion
CDK4 mutations represent a distinct subset of NSCLC. Next generation sequencing showed that CDK4 mutations commonly co-existed with other driver genes. Our results show that CDK4 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through CDK4 inhibitior palbociclib might offer new opportunities.
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P57 - Tumor Biology and Systems Biology - Basic and Translational Science - DNA Repair (ID 195)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P57.01 - Prevalence MSH6 Mutations in East Asian Non-Small Cell Lung Cancer Patients (ID 824)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
The DNA mismatch repair (MMR) pathway is one of the cell defense mechanisms by which mutations that spontaneously arise during replication and recombination are corrected to maintain genomic integrity. Defects in the MMR genes (MLH1, MSH2, MSH6 and PMS2) lead to genomic instability. MSH6 gene (HGNC_ID:7329) is located in chromosome 2 (2p16) codes for an MSH6 protein in humans. The MSH6 protein contains Walker-A/B adenine nucleotide binding motif (150 amino acids). The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring MSH6 mutations.
Methods
A total of 842 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MSH6 mutations and other genes were detected by next generation sequencing.
Results
MSH6 gene mutation rate was 3.21% (27/842) in non-small cell lung cancer, including E1163V (3 patient), S346C (3 patient), G355S (2 patient), A37G (2 patient), T1225M (2 patient), S144I (2 patient), K1358Dfs*2 (2 patient), Y642C (1 patient), A48V (1 patient), L735P (1 patient), K854M (1 patient), D116G (1 patient), Q572H (1 patient), F1088Lfs*5 (1 patient), S309Y (1 patient), N184S (1 patient), T767S (1 patient) and F1088Sfs*2 (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were MSH6 gene with co-occurring mutations. Briefly, patients with (n=5) or without (n=22) co-occurring EGFR mutations had a median OS of not up to now and 14.0 months respectively (P=0.27); patients with (n=16) or without (n=11) co-occurring TP53 mutations had a median OS of 14.0 months and 19.0 months respectively (P=0.33); patients with (n=11) or without (n=16) co-occurring KRAS mutations had a median OS of 14.0 months and 19.0 months respectively (P=0.09); patients with (n=4) or without (n=23) co-occurring KMT2C mutations had a median OS of not up to now and 14.0 months respectively (P=0.36).
Conclusion
MSH6 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to immunotherapy in patients with NSCLC.
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P59 - Tumor Biology and Systems Biology - Basic and Translational Science - Genomics (ID 197)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P59.01 - AR Mutations Defines a Unique Molecular Class of Non-Small Cell Lung Cancer in East Asian Patients (ID 857)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
Epidemiology of non-small-cell lung cancer (NSCLC) differs between genders and it might be partially explained by different gender hormone levels in female and male. There are some epidemiological data indicating that gender is a significant, independent prognostic factor in NSCLC with AR (Androgen receptor). The aim of this study is to investigate mutations and prognosis of NSCLC harboring AR mutations.
Methods
A total of 509 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of AR mutations and other genes were detected by next generation sequencing.
Results
AR gene mutation rate was 1.77% (9/509) in non-small cell lung cancer, including T756S (1 patient), E355K (1 patient), T919N (1 patient), Q734H (1 patient), E773Q (1 patient), A45T (1 patient) , A141T (1 patient), D840H (1 patient) and D308H (1 patient), and median overall survival (OS) for these patients was 21.0 months. Among them, all patients were AR gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=5) co-occurring EGFR mutations had a median OS of 16.5 months and 21.0 months respectively (P=0.84); patients with (n=6) or without (n=3) co-occurring TP53 mutations had a median OS of 20.5 months and 21.0 months respectively (P=0.88); patients with (n=5) or without (n=4) co-occurring SMARCA4 mutations had a median OS of 20.0 months and 21.0 months respectively (P=0.50); patients with (n=3) or without (n=6) co-occurring CDKN2A mutations had a median OS of 21.0 months and 20.0 months respectively (P=0.72).
Conclusion
Althoght EGFR, TP53, SMARCA4, CDKN2A gene accompanied may have less correlation with AR mutation in NSCLC patients, predict which patients may harbor AR mutations, could have implications in triaging toward AR variant identification for potential future targeted therapy. These data have implications for the identification of therapeutic target candidates.
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P70 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/OTHERS (ID 210)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 5
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P70.01 - Distribution of CCND1 Mutations in East Asian Patients With Non-Small Cell Lung Cancer (ID 646)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
CCND1 is a member of the cyclin D family and promotes G1-S transition in cell proliferation. In the TransATAC substudy, breast cancers with CCND1 amplification were found to have a poor prognosis. In addition, overexpression of CCND1 demonstrates resistance to chemotherapy in vitro. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring CCND1 mutations.
Methods
A total of 661 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of CCND1 mutations and other genes were detected by next generation sequencing.
Results
CCND1 gene mutation rate was 0.61% (4/661) in non-small cell lung cancer, including E280V (1 patient), E74K (1 patient), P157A (1 patient) and T120P (1 patient), and median overall survival (OS) for these patients was 13.5 months. Among them, all patients were CCND1 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=2) co-occurring EGFR mutations had a median OS of 7.5 months and 13.5 months respectively (P=0.81); patients with (n=2) or without (n=2) co-occurring TP53 mutations had a median OS of not up to now and 13.5 months respectively (P=0.88); patients with (n=2) or without (n=2) co-occurring KRAS mutations had a median OS of 7.5 months and 13.5 months respectively (P=0.81); patients with (n=2) or without (n=2) co-occurring BRCA2 mutations had a median OS of 7.0 months and not up to now respectively (P=0.09).
Conclusion
EGFR, TP53, KRAS and BRCA2 gene accompanied may have less correlation with CCND1 mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.
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P70.02 - Clinicopathologic Characteristics and Outcomes of East Asian Patients With Non-Small-Cell Lung Cancer and FLT3 Mutations (ID 673)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
The FLT3 gene is located on chromosome 13, and FLT3 receptors comprise fve immunoglobulin-like structures, including a ligand-binding extracellular domain, a single transmembrane domain, a cytoplasmic domain containing the juxtamembrane domain (JMD), and two tyrosine kinase domains (TKDs; TKD1 and TKD2). FLT3-ITD results in an ITD in the JMD and is reportedly associated with signifcantly short remission periods and poor outcomes. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring FLT3 mutations.
Methods
A total of 417 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of FLT3 mutations and other genes were detected by next generation sequencing.
Results
FLT3 gene mutation rate was 1.44% (6/417) in non-small cell lung cancer, including R834Q (1 patient), I527T (1 patient), L104P (1 patient), Q115H (1 patient), R271S (1 patient) and K567E (1 patient), and median overall survival (OS) for these patients was 10.0 months. Among them, all patients were FLT3 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 10.0 months and 15.5 months respectively (P=0.60); patients with (n=2) or without (n=4) co-occurring KEAP1 mutations had a median OS of 8.0 months and 16.5 months respectively (P=0.06); patients with (n=2) or without (n=4) co-occurring NTRK3 mutations had a median OS of 9.0 months and 16.5 months respectively (P=0.26); patients with (n=3) or without (n=3) co-occurring PTPRD mutations had a median OS of 9.0 months and not up to now respectively (P=0.29).
Conclusion
FLT3 gene mutation coexists with other gene mutation in NSCLC. TP53, KEAP1, NTRK3 and PTPRD gene accompanied may have less correlation with FLT3 mutation in NSCLC patients. Analysis of FLT3 mutations shows promise as a way to refine individual patients with NSCLC, and provides more insight into effective treatment strategies for patients with FLT3 mutations.
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P70.03 - Molecular Characterization of AKT1 Gene in East Asian Non-Small Cell Lung Cancer Patients (ID 685)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
The AKT1 gene provides instructions for making a protein called AKT1 kinase. This protein is found in various cell types throughout the body, where it plays a critical role in many signaling pathways. The AKT1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring AKT1 mutations.
Methods
A total of 1255 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of AKT1 mutations and other genes were detected by next generation sequencing.
Results
AKT1 gene mutation rate was 0.64% (8/1255) in non-small cell lung cancer, including E418K (1 patient), R15Q (1 patient), R25Tfs*8 (1 patient), K154Nfs*97 (1 patient), T443M (1 patient), F407L (1 patient) , G159D (1 patient) and E17K (1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were AKT1 gene with co-occurring mutations. Briefly, patients with (n=6) or without (n=2) co-occurring TP53 mutations had a median OS of 9.0 months and 12.0 months respectively (P=0.64); patients with (n=2) or without (n=6) co-occurring ERBB4 mutations had a median OS of 12.5 months and 12.0 months respectively (P=0.91); patients with (n=2) or without (n=6) co-occurring EZH2 mutations had a median OS of 9.0 months and 12.0 months respectively (P=0.52); patients with (n=2) or without (n=5) co-occurring KEAP1 mutations had a median OS of 9.0 months and 12.0 months respectively (P=0.21).
Conclusion
TP53, ERBB4, EZH2, KEAP1 gene accompanied may have less correlation with AKT1 mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.
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P70.04 - Outcomes of Molecular Characteristics in East Asian IDH2-mutant Non-Small Cell Lung Cancer Patients (ID 697)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
Isocitrate dehydrogenases (IDH) 2 is key metabolic enzymes that generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) to maintain a pool of reduced glutathione and peroxiredoxin, and produce-ketoglutarate, a co-factor of numerous enzymes. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring IDH2 mutations.
Methods
A total of 893 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IDH2 mutations and other genes were detected by next generation sequencing.
Results
IDH2 gene mutation rate was 0.90% (8/893) in non-small cell lung cancer, including R172G (2 patient), R140Q (2 patient), T146Lfs*15(2 patient), S371G (1 patient) and E150K (1 patient), and median overall survival (OS) for these patients was 9.5 months. Among them, all patients were IDH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=6) co-occurring EGFR mutations had a median OS of 13.5 months and 9.5 months respectively (P=0.74); patients with (n=6) or without (n=2) co-occurring TP53 mutations had a median OS of 16.5 months and 5.5 months respectively (P=0.19); patients with (n=2) or without (n=6) co-occurring RB1 mutations had a median OS of 4.5 months and 16.5 months respectively (P=0.03); patients with (n=2) or without (n=6) co-occurring CDKN2A mutations had a median OS of 9.5 months and 13.5 months respectively (P=0.64).
Conclusion
IDH2 mutations were observed in 0.90 % of cases of NSCLC. IDH2-mutated NSCLC can exhibit other driver gene alterations. RB1 accompanied mutations might play a good prognosis in IDH2 gene mutation patients.
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P70.05 - The Association Between MAP2K1 Mutation Class and Clinical Features in MAP2K1‑Mutant East Asian Non‑Small Cell Lung Cancer Patients (ID 837)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
The MAP2K1 gene provides instructions for making a protein known as MEK1 protein kinase. This protein is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus. RAS/MAPK signaling helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring MAP2K1 mutations.
Methods
A total of 793 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MAP2K1 mutations and other genes were detected by next generation sequencing.
Results
MAP2K1 gene mutation rate was 1.77% (14/793) in non-small cell lung cancer, including Q56P (2 patient), D351G (2 patient), H119Y (2 patient), R160K (1 patient), R234T (1 patient), E120D (1 patient), P124L (1 patient), C207S (1 patient), A283S (1 patient), E102_I103del (1 patient) and Q354H (1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were MSH6 gene with co-occurring mutations. Briefly, patients with (n=9) or without (n=5) co-occurring TP53 mutations had a median OS of 12.0 months and not up to now respectively (P=0.41); patients with (n=3) or without (n=11) co-occurring KRAS mutations had a median OS of not up to now and 12.0 months respectively (P=0.33); patients with (n=4) or without (n=10) co-occurring KRAS mutations had a median OS of 14.5 months and 12.0 months respectively (P=0.57); patients with (n=4) or without (n=23) co-occurring STK11 mutations had a median OS of 11.5 months and 12.0 months respectively (P=0.70).
Conclusion
MAP2K1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of MAP2K1 aberrations is critical for the identification of therapeutic target candidates.
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P73 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/FGFR (ID 209)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P73.01 - Clinicopathologic Characteristics and Survival Outcome in East Asian Patients With Non-Small Cell Lung Cancer and FGFR2 Mutations (ID 690)
00:00 - 00:00 | Author(s): Tangfeng Lv
- Abstract
Introduction
Activation of the fibroblast growth factor receptor (FGFR) family through fusion with various partners has been described in multiple cancer types, including non-small-cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring FGFR2 mutations.
Methods
A total of 1124 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of FGFR2 mutations and other genes were detected by next generation sequencing.
Results
FGFR2 gene mutation rate was 1.69% (19/1124) in non-small cell lung cancer, including R6P(4 patient), N184Efs*16(2 patient), L753F(1 patient), G302R(1 patient), E755Q(1 patient), W72C(1 patient), A315T(1 patient), P725R(1 patient), G89W(1 patient), A362V(1 patient), V12M(1 patient), P582L(1 patient), P583(1 patient), P493L (1 patient) and N95Efs*16(1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were FGFR2 gene with co-occurring mutations. Briefly, patients with (n=15) or without (n=4) co-occurring TP53 mutations had a median OS of 8.0 months and 28.0 months respectively (P=0.23); patients with (n=7) or without (n=12) co-occurring KEAP1 mutations had a median OS of 6.5 months and 12.0 months respectively (P=0.45); patients with (n=3) or without (n=16) co-occurring STK11 mutations had a median OS of 17.5 months and 12.0 months respectively (P=0.77); patients with (n=3) or without (n=16) co-occurring SMARCA4 mutations had a median OS of 20.0 months and 12.0 months respectively (P=0.67).
Conclusion
FGFR2 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to target therapy in patients with NSCLC.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.34 - Exosomal miRNAs Participate in Osimertinib Resistance Mainly Through Bypass Activation Mechanisms in Non-Small Cell Lung Cancer (ID 1676)
00:00 - 00:00 | Presenting Author(s): Tangfeng Lv
- Abstract
Introduction
Osimertinib, the third generation of EGFR-TKI has become an important treatment option for patients with EGFR-mutant advanced NSCLC. In recent years, more and more studies have begun to pay attention to the function of miRNAs in exosomes secreted by tumor cells to transmit resistance information. Especially miRNAs in exosomes, participate in the resistance mechanism of third-generation EGFR-TKI Osimertinib which is still unknown.
Methods
We constructed a drug-resistant cell line H1975-OR, and collected the exosomes from the cells of the drug-resistant strain and the sensitive strain, and extracted respective RNA for sequencing. We also compared miRNAs in serum exosomes of three patients before and after resistance to Osimertinib. Enlarged samples were then validated in 64 NSCLC patients.
Results
Cluster analysis of target genes revealed that miRNAs in exosomes participate in Osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality, PI3K pathway activation). Exosomes miR-184, miR-3913-5p, miR-3614-5p, and miR-4746-5p could be promising diagnostic biomarkers for NSCLC patients. After patients with Osimertinib resistance, miR-184 and miR-3913-5p increased significantly in serum exosomes. MiR-184 and miR-3913-5p increased significantly in serum exosomes of patients with later Osimertinib resistance. These two miRNAs mainly cause EGFR resistance in two types of NSCLC patients, EGFR exon 21 L858R mutation and T790M positive. They might be important molecules that transmit Osimertinib resistance.
Figure 1. Isolation and identification of exosomes from cell supernatant. (A) The drug-resistant strain H1975-OR was obtained by continuous exposure to H1975 for 6 months. The cell viability was measured using the MTT method.(B) The average IC50 values of H1975 and H1975-OR were 4636 nM and 12101 nM, respectively, with significant differences (p=0.0215).(C) Observation of extracellular vesicles extracted from the cell supernatant by the transmission electron microscope, with a size between 30-150 nm. Scale = 200nm.(D) Particle size analysis shows exosomal size distribution.(E) The expression of TSG101 and CD63 in supernatant-derived exosomes of the two cells was detected by western blot, and 20 μg of protein was loaded each.
Conclusion
Exosomes miR-184 and miR-3913-5p are key molecules involved in resistance to Osimertinib, and may participate in resistance through a mechanism of alternative activation.
