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C. Hu
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-008 - Snai1-Expression Cancer-Associated Fibroblast Induce Epithelial-Mesenchymal Transition of Lungcancer Cells through miR-33b (ID 8390)
09:30 - 09:30 | Author(s): C. Hu
- Abstract
Background:
Lung cancer patients often have poor prognosis, on account of high propensity for metastasis. Cancer-associated fibroblasts (CAFs) are the main type of stromal cells in lung cancer tissue, which are activated by tumor cells, play a significant role in tumor development. However, it is uncertain whether CAFs induce lung cancer cells metastasis and which pathway is involved. Snail1 is a transcriptional factor and its expression in the stroma associates with lower rates of survivors in cancer patients. Nevertheless, it has not been determined how Snail1 regulate the crosstalk between stromal and tumor cells when it expresses in stroma. Altered expression of microRNA (miRNA) correalates with lung carcinogenesis and metastasis. Our previous study of miRNAs showed that the level of miR-33b was obviously decreased in lung adenocarcinoma cell lines and lung cancer tissues, and when miR-33b was elevated, it can suppressed tumor cell growth and EMT in vitro and in vivo experiments.
Method:
(1) We co-culcured four different human lung cancer cells (A549, H1299, SPC-a-1, LTEP-a-2) with control medium, NFs and CAFs，then we examined lung cancer cells motility, migration, invasion, miR-33b expression level, relevant mRNAs and proteins expression levels. (2) A549 and H1299 cells was transfected with miR-33b mimics or with miR-NC prior to CAF stimulation, then subjected to wound healing assay, Transwell assay, qRT-PCR, immunoblotting assay. (3) Using coculture lung cancer cell lines with SNAI1 transfected CAFs models, we explore the role of Snail1 in CAFs cells.
Result:
(1) Cocultivation of CAFs with lung cancer cells induced downregulation of miR-33b in lung cancer cells and promoted epithelial cells epithelial-mesenchymal transition (EMT). (2) MiR-33b overexpression by transfecting cancer cells with miR-33b mimics reverted CAFs induced EMT. (3) Transfection of CAFs with SNAI1 enhanced CAFs modulation on lung cancer cells EMT when CAFs co-cultured with A549 and H1299 cells, whereas si-SNAI1 attenuated CAFs modulation role.
Conclusion:
The induction of cancer cells EMT by CAFs is a key mechanism underlying the acquisition of cancer cells aggressive propensity. And CAFs induce lung cancer cells EMT in a miR-33b-mediated manner. Expression of Snail1 in fibroblasts was essential for the induction effect of CAFs on lung cancer cells EMT.
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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)
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P3.01-052 - The Prevalence and Genotype Distribution of Dual in Cis EGFR Mutations in Chinese Advanced Non-Small Cell Lung Cancer Patients (ID 9721)
09:30 - 09:30 | Author(s): C. Hu
- Abstract
Background:
The prevalence of EGFR mutation has been well elucidated in different ethnicities. Recently, increasing attention has been given to dual EGFR mutations. However, less attention has been invested in dual in cis EGFR mutations. Until now, none of retrospective or prospective research has focused on dual in cis EGFR mutations except case reports.
Method:
In this real world study, we performed capture-based ultra-deep targeted sequencing on circulating tumor DNA to identify and investigate the prevalence and genotype distribution of dual in cis EGFR mutations in 3,000 Chinese advanced NSCLC patients. This cohort consisted of both treatment-naïve and previously treated patients. Ten milliliter of peripheral blood was collected from every patient and a minimum of 50ng of ctDNA was needed for library construction. The panel covered critical exons and introns of 168 genes (160kb of human genomic regions).
Result:
1,266 patients harbored EGFR mutant in this cohort; among them, 501 patients harbored 19 deletions, 489 harbored L858R, and the remaining harbored other EGFR mutations. We identified 1.5% patients (19/1,266) harboring dual in cis EGFR mutations. Among them 37% (7/19）carried two rare EGFR mutations and the remaining 63% (12/19) carried EGFR L858R in combination with a rare mutation. No patient carried EGFR 19 del in combination with other rare mutations was identified in this cohort, suggesting EGFR 19del is a stronger oncogenic driver than EGFR L858R (p=0.000197, Fisher’s exact test). For patients carried two rare mutations, both mutations were either located on exon 18 or exon 21. The allelic fractions (AF) of both mutations were similar. The AF of either EGFR mutations was the maximum AF in all patients, demonstrating the clones harboring EGFR mutations were major clones. Interestingly, 1 patient carried additional KRAS mutation and 2 patients had EGFR amplification.
Conclusion:
In cis dual EGFR mutation was rare (1.5%) in EGFR mutant Chinese advanced NSCLC patients. EGFR L858R was significantly more likely to couple with a rare in cis dual mutation than 19 del. EGFR 19del might be a stronger oncogenic driver than EGFR L858R.
