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C. Xie
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MA02 - RNA in Lung Cancer (ID 377)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 1
- Moderators:E. Brambilla, M. Noguchi
- Coordinates: 12/05/2016, 14:20 - 15:50, Stolz 2
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MA02.07 - Evaluation of Exosomal miRNAs from Plasma as Potential Biomarker for NSCLC (ID 5120)
15:08 - 15:14 | Author(s): C. Xie
- Abstract
- Presentation
Background:
Non-small-cell lung cancer (NSCLC) is one of the most common and high mortality rate carcinoma in China which biomarkers for diagnosis are limited. Therefore, novel biomarkers and methods with increased specificity for diagnosis are explored and required. For now, liquid biopsy for lung cancer oncogenes and next generation sequencing technique are extensive employed in NSCLC. However, increasing evidence illustrates that exosomal microRNAs in circulating fluids provide a promising way as biomarkers for noninvasive cancer diagnosis. Exosomes are 30–150 nm particles which are released from cells into the extracellular environment and stable miRNAs have been identified in plasma exosomes, which play important role in cell communication. Furthermore, exosomal miRNAs present different profiles between patients with cancer and healthy individuals. Whether exosomal miRNAs could benefit NSCLC patient diagnosis remains to be explored.
Methods:
Blood samples were collected from 40 NSCLC patients and 24 healthy volunteers matched with age, gender and blood collection time. Plasma exosomes were accessed by 110,000×g ultracentrifugation and visualized by NS300 equipment. The raw data of exosomal miRNA profiles of NSCLC patients and healthy individuals were generated by NGS around 400× read depth and its expression were measured by Taqman probe quantitive PCR
Results:
In the present study, we revealed that nearly half of exosome RNA was miRNA and NSCLS patients expressed a set of exosomal miRNAs with specificity compared with healthy volunteers. We demonstrated that miR-126-5p and miR-21-3p were down-regulated in NSCLC patients. In addition, we showed that the expression level of miR-124-3p and miR-99a-3p in NSCLC patients was higher than that of healthy individuals. Furthermore, we found miR-99a-3p was clinical stages related in NSCLC patient plasma and miR-375-3p was a potential biomarker for diagnosis and prognosis in NSCLC.
Conclusion:
Exosomal miRNAs in plasma could indicate the progress of NSCLC and a combination of the explored miRNA could serve as a promising biomarker for NSCLS diagnosis and prognosis.
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-033 - Exosomal Proteomics Analysis Reveal New Targets for Radiation-Induced Lung Toxicity Diagnosis (ID 5121)
14:30 - 14:30 | Author(s): C. Xie
- Abstract
Background:
radiation-induced lung toxicity (RILT) are observed today in patients who have undergone thoracic irradiation for the treatment of lung malignancy. Radiation-induced damage to normal lung parenchyma remains the dose-limiting factor in chest radiotherapy. However, the radiative dosage is not effective for most of patients because of avoiding RILT. Therefore, novel diagnosis methods reveal individual potential RILT are required. For now, increasing evidence illustrates that exosomes in circulating fluids provide a promising way as biomarkers for noninvasive disease diagnosis. Exosomes are 30–150 nm particles which are released from cells into the extracellular environment and thousands of proteins have been identified in plasma exosomes. Whether exosomal proteomics analysis could benefit lung cancer patients with appropriate radiative dosage and prevent RILT remains to be studied.
Methods:
Plasma samples were collected from RILT patients with grade I and II, and no RILT individuals matched with age, gender and blood collection time after 10 to 30Gy radiation within 6 months. Plasma exosomes were accessed by 110,000×g ultracentrifugation and visualized by NS300 equipment. The raw data of exosomal proteomics profiles of RILT patients and no-RILT individuals were generated by LC-MS and its expression were verified by western blot.
Results:
In the present study, we revealed 17 exosomal protein participated in wounding response and two of them were correlated with RILT clinic stage. A2M (Alpha-2-macroglobulin) was decreased in RILT patients and FGB (Fibrinogen beta chain) was increased in RILT patients. Furthermore, A2M was decreasing from no radiative damage patients to that of RILT grade I to II, and the FGB expression in exosomes showed positive correlation with RILT from low to high level. The patients with low FGB expression in plasma exosomes could tolerate higher radiative dosage until the FGB was upregulated in plasma.
Conclusion:
LC-MS is an efficient method for exosomal proteomics analysis and we reveal two stable targets A2M and FGB, which could indicate the potential of patients suffering RILT after radiotherapy. The two novel targets could serve as promising diagnosis biomarkers for avoiding RILT.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-002 - Treatment Outcome Comparison between Exon 19 and 21 EGFR Mutations after Second-Line TKIs in Advanced NSCLC Patients (ID 5113)
14:30 - 14:30 | Author(s): C. Xie
- Abstract
Background:
Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity. The sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. the purpose of this study is to investigate the clinical outcome of NSCLC patients with and without brain and/or bone metastases in different EGFR tumor genotypes receiving EGFR-TKIs as a second-line treatment.
Methods:
The treatment outcomes of 166 NSCLC patients harboring either the exon 19 deletion or the L858R point mutation of EGFR treated by second-line TKIs were retrospectively reviewed.
Results:
The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. The median PFS and OS for NSCLC patients with bone metastasis were 4.8 months (95% Cl, 4.0-5.6 months) and 12.9 months (95% Cl, 8.7-17.1 months), respectively. No significant difference was observed for patients with bone metastasis for different mutations. EGFR genotype and ECOG PS were independent predictors of PFS for both NSCLC patients with and without brain metastasis. Never smoking (P=0.001), exon 19 deletion (P=0.03), EGOC PS (0-1) (P<0.001) and no brain metastasis (p=0.01) were correlated with longer OS for all NSCLC patients. For patients with brain metastasis, age at disease progression (p=0.009), genotype (p=0.02) and EGOC PS (p<0.001) were independent predictors of OS. For patients with bone metastasis, EGOC PS (p<0.001) was an independent predictor for both PFS and OS. Female (P=0.01), never smoking (P=0.005), number of bone metastases (P=0.03) and EGOC PS (0-1) (P=0.002) were related to a longer PFS. EGOC PS (0-1) (P<0.001) was associated with a longer OS. Rash, fatigue, and anorexia were the three most frequent side effects observed No significant side effects difference between exon 19 and 21 mutation groups were observed.
Conclusion:
NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutations are significant prognostic factors for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment.
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P3.02b-089 - Treatment of NSCLC Patients with Malignant Pleural Effusion Harboring Exon 19 and 21 EGFR Mutations after First-Line and Second-Line TKIs (ID 5114)
14:30 - 14:30 | Author(s): C. Xie
- Abstract
Background:
Recent studies demonstrated a significantly increased frequency of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs). However, the sensitivity of tyrosine kinase inhibitors (TKIs) in NSCLC patients with MPE for different EFGR mutations was less reported. The purpose of this study is to investigate the effect of first-line and second-line EGFR-TKIs in the treatment of NSCLC with MPEs harboring exon 19 deletion and L858R mutation.
Methods:
From 2010 to 2015, 203 NSCLC patients with MPEs harboring EGFR mutation treated with EGFR- TKIs were reviewed. The efficacy were evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model.
Results:
The objective response rate (ORR) and disease control rate (DCR) for patients treated with first-line and second-line EGFR-TKIs were 21.9%, 91.4% and 14.7%, 85.3%, respectively. The overall median PFS and OS of enrolled NSCLC patients with MPE were 9.3 months (95% Cl, 8.4-10.2 months), 20.9 months (95% Cl, 18.9-22.9 months) after first-line TKIs, and 7.6 months (95% Cl, 6.6-8.6 months), 15.3 months (95% Cl, 13.6-15.9 months) after second-line TKIs, respectively. The exon 19 deletion arm had a longer median PFS (9.4 vs. 7.1 months, p=0.003) and OS (16.8 vs. 13.8 months, p=0.003) compared with the L858R mutation arm after second-line TKIs. ECOG PS (PFS: P=0.004; OS: P=0.01) and TNM stage (PFS: P<0.001; OS: P=0.002) were independent predictors of PFS and OS for NSCLC patients with MPE treated by first-line TKIs. ECOG PS (0-1) (PFS: p=0.004; OS: p<0.001) , TNM stage (Ⅳa) (PFS: p=0.04; OS: p=0.007) and exon 19 deletions (PFS: p=0.02; OS: p=0.02) were related to a longer PFS and OS for patients treated with second-line TKIs. Gender was also an independent predictor of OS (p=0.04) for patients treated with second-line TKIs. There was no significant difference on side effects between NSCLC patients with exon 19 and 21 mutations in the first or second-line EGFR-TKIs.
Conclusion:
EGFR genotype was an independent predictor of PFS and OS. No significant side effects differences between the two mutation groups was observed for first or second-line EGFR-TKIs. This study demonstrated that EGFR mutations are significant predictors for advanced NSCLC patients with MPE receiving second-line EGFR-TKIs treatment.
