Virtual Library
Start Your Search
C. Choi
Author of
-
+
P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.01-034 - Liquid Biopsy for EGFR Genotyping Using Cell-Free DNA and Extracellular Vesicular DNA of Pleural Effusion in Pulmonary Adenocarcinoma Patients (ID 9201)
09:30 - 09:30 | Author(s): C. Choi
- Abstract
Background:
Pleural effusion is a highly efficient sample for liquid biopsy due to cancer cell enriched components. Liquid biopsy for EGFR genotyping is mostly being done using cell-free DNA. Extracellular vesicles (EVs) are known to carry oncogenic double stranded DNA that is considered as a noble biomarker. We set up to investigate the liquid biopsy using cell-free (cf) DNA and extracellular vesicular (EV) DNA of pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients.
Method:
Forty nine pleural effusion samples of pulmonary adenocarcinoma patients were evaluated. Non-cellular components after removing cell pellets by centrifuge (400g, 10 min, 4[0]C) were used for liquid biopsy and EVs were isolated by ultracentrifuge method (200,000g, 1 hr, 4[o]C). EV DNA and cf DNA were extracted separately and EGFR genotyping was done by PNA-clamping method. For the analysis of T790M detection, cell block slides were used as rebiopsy sample, when compared with liquid samples.
Result:
Among 31 EGFR-TKI naïve patients with known tissue EGFR genotyping, liquid biopsy using effusion EV DNA showed 100% matching with tissue EGFR genotyping in 19 EGFR mutant cases and detected 3 more EGFR mutant cases in tissue wild type (WT) patients, while liquid biopsy using effusion cf DNA missed 2 cases of tissue-based EGFR mutant patients and found 2 more EGFR mutant cases in tissue WT patients. In 18 patients with acquired resistance to EGFR-TKI, EGFR genotyping using effusion EV DNA detected T790M mutation in 13 of 18 (72.2%) patients, while 11 of 18 (61.1%) patients were detected by using effusion cf DNA, respectively. In contrast, only 3 patients were found to have T790M when using cell block slides.
Conclusion:
Liquid biopsy using pleural effusion is particularly effective for EGFR genotyping than conventional cytology or cell block sample. Liquid biopsy using effusion EV DNA is highly promising for EGFR genotyping, especially detecting T790M mutation, when compared with cf DNA.
-
+
P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.02-088 - Enhanced Glycolysis Is Critical for Maintaining Inactivation of JNK and Stability of EGFR Leading to the Survival of EGFR-Mutant Lung Cancer Cells (ID 8134)
09:30 - 09:30 | Author(s): C. Choi
- Abstract
Background:
Metabolic reprogramming is required for cancer cells to meet the demands of enhanced cell proliferation. In this study, we investigated how altered cell metabolism is associated with oncogenic mutant EGFR in lung cancer.
Method:
Metabolomics and measurement of metabolites in glycolytic pathway and TCA cycle were done using lung cancer cells with mutant EGFR and wild-type EGFR.
Result:
EGFR-mutant lung cancer cells showed enhanced glycolysis with elevated glucose uptake and lactate production which resulted in high extracellular acidification rate compared to cancer cells with wild-type EGFR. EGFR-TKI treatment or knockdown of EGFR caused a significant decrease in the metabolites of glycolysis. They are much more sensitive to glucose deprivation, but not to glutamine deprivation. Glutamine is usually utilized to fuel the TCA cycle supporting tumor cell growth. However, glucose was the main source of TCA cycle to produce ATP in EGFR-mutant cells. This mutant EGFR-enhanced glycolysis was critical for EGFR stability. The failure to sustain ATP production in mitochondria by glucose deprivation or suppression of glycolysis induced ROS accumulation which resulted in JNK activation. Activated JNK mediated EGFR degradation causing apoptosis while SP600125, a JNK inhibitor, could rescue cells from apoptotic cell death. Importantly, almost same effects could be observed in EGFR-TKI-resistant cells by T790M.
Conclusion:
Together, our data showed that EGFR-mutant lung cancer cells require the enhanced glycolysis for maintaining inactivation of JNK and EGFR stability regardless of T790M. This could be an attractive target for treatment of EGFR-mutant lung cancer, especially with resistance to EGFR-TKI.
