Virtual Library
Start Your Search
Xiaotong Duan
Author of
-
+
EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.03-08 - MiR-744 Facilitates Non-Small Cell Lung Cancer Progression by Transcriptional Regulation of c-FOS (Now Available) (ID 1806)
08:00 - 18:00 | Author(s): Xiaotong Duan
- Abstract
Background
Metastasis is the leading cause of lung cancer associated death. Here, we focused on the function and downstream molecular mechanism of miR-744 and its potential clinical application in non-small cell lung cancer (NSCLC) progression.
Method
The clinical cohort and data from TCGA were analyzed for the correlation of miR-744 and clinical outcomes. Multiple NSCLC cell lines and a NSCLC xenograft model were applied for the functional studies in vitro and in vivo respectively. Reporter assays were used for transcriptional regulatory mechanism study.
Result
It was confirmed that the overexpression of miR-744 was significantly correlated with lymph node metastasis and poor prognosis in NSCLC. It was an independent prognostic molecular marker for NSCLC. Both in vitro and in vivo studies revealed that miR-744 overexpression aggravated the invasion and metastasis of NSCLC cells. MiR-744 positively regulated c-FOS by directly binding to the promoter of c-FOS. We also identified -358 to -332 bp and -221 to -192 bp upstream of c-FOS gene as the direct and efficient miR-744 binding site in c-FOS promoter region. MicroRNA-744 could regulate MAPK signaling and enhanced the resistance of lung cancer cells to radiotherapy and paclitaxel.
Conclusion
Our findings uncover the function of miR-744 in NSCLC and reveal a novel mechanism of miR-744 in mediating growth and metastasis of NSCLC cells. Our data suggests that miR-744 may serve as a possible therapeutic target for NSCLC. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.
-
+
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.01-37 - Radiotherapy Changed the Subclonal Composition of Brain Metastasis from Non Small Cell Lung Cancer: NGS-Based Analysis of Cerebrospinal Fluid (ID 544)
09:45 - 18:00 | Author(s): Xiaotong Duan
- Abstract
Background
Radiotherapy（RT） is an effective treatment for brain metastasis (BM) of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) can be used for dynamic monitoring the oncogenic mutations of BM from NSCLC.
Method
A total of 22 CSF samples from 8 patients with BM from NSCLC were collected at three time points（before the start, in the middle and at the end of RT）and analyzed using NGS.
Result
Five patients (D01, D03, D04, D07, D08) exhibited a significantly decreased mutation number after RT, and new mutation was detected in two patients (D03, D07). A large number of new copy number variations (CNVs) were detected after RT in one patient (D06), and the mutation abundance of the primary clone also increased significantly. One patient (D08) showed a slight increase in mutation abundance of the primary clone after RT. Mutation detections at all time points were negative in two patients (D02, D05).
Patients
gender
Pathology
Baseline mutation status
(Sample type)
Radiotherapy
regime
concurrent systematic treatment
Brain metastasis
Changes of CSF mutation status
Pre-radiation
Post-radiation
Common driven mutation
mutation abundance
mutation number
New mutations
D01
Male
Squamous cell carcinoma
Unknown
SIB-IMRT:
WBRT 40Gy/20F, GTV 56Gy/20F
No
Newly diagnosed
No
↓
↓
No
D02
Female
Adenocarcinoma
C-MET（+++）
(Tissue from BM)
SIB-IMRT:
WBRT 40Gy/20F, GTV 56Gy/20F
Pem+Cis
Newly diagnosed
No
—
—
—
D03
Male
Adenocarcinoma
EGFR 19-Del
(Tissue from lung lesion)
SIB-IMRT:
WBRT 36Gy/20F, GTV 54Gy/20F
Erlotinib
Newly diagnosed after TKI
No
↓
↓
EGFR 19del
D04
Male
Unknown
Unknown
3D-CRT:
WBRT 40Gy/20F
No
Newly diagnosed
EGFR 19-Del
↓
↓
No
D05
Female
Adenocarcinoma
EGFR 19-Del
(Tissue from lung lesion)
SIB-IMRT:
WBRT 36Gy/20F, GTV 56Gy/20F
Erlotinib
Progressed after TKI
No
—
—
—
D06
Male
Adenocarcinoma
EGFR 21 L858R（+）
(Tissue from lung lesion)
WBRT 40Gy/20F
SRS 16Gy
Erlotinib
Progressed after TKI
EGFR 21 L858R（+）
↓ at first and then ↑
↑
CNVs
D07
Female
Adenocarcinoma
EGFR 21 L858R（+）
(Blood plasma)
3D-CRT:
WBRT 30Gy/10F
No
Newly diagnosed after TKI
EGFR 21 L859R（+）
MET amp
↓
↓
MAP3K13 p.R585Q
D08
Female
Adenocarcinoma
ALK(+)
(Tissue from lung lesion)
SIB-IMRT:
WBRT 40Gy/20F, GTV 56Gy/20F
Crizotinib
Newly diagnosed after TKI
ALK(+)
slightly ↑
↓
No
M:Male, F: Female, SCC:Squamous carcinoma, AD: Adenocarcinoma, NO: Unknown, ND:Newly diagnosed, PD: Progressed, N: No, E: Erlotinib
Figure 1.Mutation profiling of CSF
Conclusion
RT changed the subclonal composition of BM from NSCLC. Further timing mutational process during RT may provide insight into the optimization of the combination of RT and targeted therapy for BM from driven mutation-positive NSCLC. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.
-
+
P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.03-59 - The Role of Radiation Dose-Dependent Lipid Metabolism Reprogramming on Radiation Survival/Resistance in Lung Cancer Cells (ID 2051)
10:15 - 18:15 | Author(s): Xiaotong Duan
- Abstract
Background
Radiotherapy plays a more and more important role in the management of lung cancer. However, radioresistance still limits the long-term control of tumors. Exploration of the dynamic changes of metabolic reprogramming in surviving/resistant lung cancer cells exposed to increased doses of radiation is helpful to elucidate the metabolic mechanism of radiation resistance in lung cancer cells, to develop new targets for the clinical intervention and the early detection of radiation resistance.
Method
Lung cancer cells A549, H520 and H460 were treated in vitro with fractionated radiation (2 Gy) to a cumulative total dose of 40Gy, 60Gy or 80Gy. Cellular radiation sensitivity was verified by colony survival assay and comet experiments. Cell proliferation was determined by EdU assay. Transcriptome sequencing and metabolomic analysis were performed to identify differentially expressed genes and metabolites in radiation-resistant cells and their parental cells. Oil Red O staining was used to detect lipid droplet content. RT-PCR and WB were used to detect the expression of genes related to lipid metabolism.
Result
Lung cancer cell sublines that had been exposed to 20, 30 or 40 fractions of 2Gy had a significant increase in radioresistance as compared with their parental cells. Furthermore, this radioresistance of cells increased with the increase of previous radiation dose exposure. We found that lipid droplet deposition and the expression of lipid metabolism genes, such as fatty acid oxidation-related genes and glycerol metabolism-related genes, showed an increasing trend with previous radiation dose in surviving/resistant lung cancer cells exposed to radiation. Metabolomic analysis revealed that lipid metabolites such as glycerol and oxaloacetic acid also increased significantly. Inhibition of carnitine palmitoyltransferase 1A (CPT1A) by Etomoxir, a fatty acid oxidation inhibitor, significantly enhanced the radiosensitivity and decreased the DNA repair ability of various surviving/resistant lung cancer cells exposed to radiation.
Conclusion
The surviving/resistant lung cancer cells generated by sequential irradiation provide models for future investigations of the dose-dependent mechanisms of radioresistance in a preclinical setting. Radiation dose-dependent lipid metabolism reprogramming may contribute to radiation survival/resistance in lung cancer cells. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.
