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Min Li
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-037 - Circulating Tumor DNA Clearance During Treatment Associates with Improved Progression-Free Survival (ID 9653)
09:30 - 16:00 | Author(s): Min Li
- Abstract
Background:
Therapeutic selection has been shown to lead to marked clonal evolution, thus revealing limitations in imaging scan as a monitoring method, which does not reflect biological processes at a molecular level. However, currently, response assessment of patients with non-small cell lung cancer (NSCLC) primarily relies on imaging scans, necessitating the development of methodologies for dynamic monitoring of treatment response. We evaluated ctDNA as a tumor clonal response biomarker.
Method:
We screened 831 advanced NSCLC patients with a mixture of prior treatment exposure by performing capture-based ultra-deep targeted sequencing on plasma samples using a panel consisting of 168 NSCLC-related genes. Eighty-six patients with driver mutations and a minimum of 2 evaluation points in addition to baseline were included for further analysis.
Result:
At baseline, 79.9% patients harbored at least one mutation from this panel; the remaining 20.1% had no mutation detected. Sixty-nine percent of patients (570/831) harbored driver mutation. Patients harboring 2 mutations or fewer at baseline had a median progression-free survival (PFS) of 7.4 months; in contrast, patients harboring more than 2 mutations had a median PFS of 3.8 months (P=6.6x10[-5 ]HR=0.34), suggesting a significant inverse correlation between number of mutations at baseline and PFS. Next, we evaluated the ability of ctDNA as a tumor clonal response biomarker in 86 patients with a minimum of 2 follow-ups. After a median follow-up of 314 days, 64 patients (74.4%) reached disease progression. During treatment, 46 patients, treated with either matched targeted therapy (MTT) or chemotherapy, had a minimum of one time of ctDNA clearance, occurring from 1.6 months to 7.5 months after the commencement of treatment, with a median PFS of 8.07 months, an overall response rate (ORR) of 41% and a disease control rate (DCR) of 93%. Median overall survival (OS) for this group has not reached. In contrast, 40 patients who had consistent detectable ctDNA throughout the course of treatment had a median PFS of 3.47months, a median OS of 425 days, an ORR of 20% and a DCR of 53%. Our data revealed that patients with a minimum of one time ctDNA clearance are associated with a better ORR (p=0.05), DCR (p=5.9x10[-5]), a longer PFS (p=5.4x10[-10 ]HR=0.21) and OS (p=2.3x10[-5 ]HR=0.21), regardless the type of treatment commenced and the time of evaluation.
Conclusion:
This real world study comprising a heterogeneous population reveals the predictive and prognostic value of ctDNA and warrants further investigations to explore its clearance as a surrogate endpoint of efficacy.
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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 - 16:00 | Presenting Author(s): Min Li
- 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.
