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Z. Zhang
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-004 - Long Non-Coding RNA XLOC_000090 Promotes Lung Cancer Migration Through Modulation of miR-4505 (ID 9285)
09:30 - 09:30 | Author(s): Z. Zhang
- Abstract
Background:
Many studies have shown that long non-coding RNAs (lncRNAs) are implicated in cancer progress including lung cancer. In our previous studies, we screened the differentially expressed lncRNAs between lung adenocarcinoma with lymph node metastasis and lung adenocarcinoma without lymph node metastasis by microarray analysis. XLOC_000090, an lncRNA without a known function, was identified. Here, we investigated the functions of XLOC_000090 in lung cancer.
Method:
The expression of XLOC_000090 was detected by qRT-PCR in 96 pairs of NSCLC tissues and the adjacent normal lung tissues. Then, we investigated the correlation between XLOC_000090 expression and clinicopathological variables and prognosis. Cell invasion and migration assay was used to detect cell invasion and migration ability in vitro. Murine model of lung cancer was used to detect the effect of XLOC_000090 on pulmonary metastasis in vivo. Dual luciferase reporter assay was used to determine the direct binding between XLOC_000090 and miR-4505.
Result:
Compared with normal lung tissues, XLOC_000090 expression was higher in NSCLC tissues (P<0.05). XLOC_000090 expression was associated with lymph node metastasis (P<0.05) and pathological stage (P<0.05). Patients with high XLOC_000090 expression exhibited significantly poorer disease-free survival and overall survival (P<0.05). XLOC_000090 overexpression increased tumor cell migration and invasion ability, whereas downregulation of XLOC_000090 expression decreased tumor cell migration and invasion ability in both A549 and Calu3 lung cancer cells. Murine model of lung cancer also showed that XLOC_000090 promoted metastasis of lung cancer cells in vivo. Furthermore, a potential XLOC_000090-targeting miRNA, miR-4505, was identified by ceRNA regulatory network prediction analysis. miR-4505 expression was significantly downregulated in lung cells transfected with XLOC_000090, and significantly upregulated in lung cells transfected with sh-XLOC_000090. Dual-luciferase reporter assay showed the direct binding between miR-4505 and XLOC_000090. XLOC_000090-promoted cell migration and invasion ability was diminished in miR-4505 overexpressed cells.
Conclusion:
Our results demonstrated that XLOC_000090 promoted the migration and invasion of lung cancer cells through regulating miR-4505. XLOC_000090 could be served as a new molecular marker for the progression and prognosis of patients with NSCLC.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-040 - EGFR T790M Mutation Detection and Osimertinib Treatment Response Evaluation by Liquid Biopsy in Advanced NSCLC Patients (ID 9448)
09:30 - 09:30 | Author(s): Z. Zhang
- Abstract
Background:
Lung cancer remains the leading cause of cancer-related death worldwide. Though most patients with EGFR activating mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs), tumors will inevitably acquire resistance to first generation EGFR TKIs. EGFR T790M mutation accounts for about 50% of these resistance cases. Droplet digital PCR (ddPCR) and cobas enables quantification of specific mutated ctDNA. In this study, these methods were used to detect and evaluate the ctDNA response after Osimertinib treatment.
Method:
In the screening period of ASTRIS (D5160C00022) study in single center, tumor and blood samples from 69 stage ⅢB-Ⅳ NSCLC patients defined as acquired resistance to first generation EGFR TKIs (Gefitinib, Elortinib or Ecotinib) were collected. The cobas® Mutation Test v2 kit was used to detect EGFR mutations in FFPE or plasma samples. Plasma T790M mutation of both Osimertinib naïve and treated patients were quantified by Droplet digital PCR (ddPCR).
Result:
The T790M mutation rate of FFPE tissue cobas, plasma cobas and plasma ddPCR testing were 54.5%, 21.3% and 30.4% respectively. Taking the FFPE tissue cobas testing as gold standard, the sensitivity and specificity of plasma ddPCR to detect T790M mutation was 66.7% and 63.6%. Taking all testing methods into account, the T790M positive rate was 52.2%. In all of the plasma cobas positive cases, T790M mutation was detected by ddPCR. In 10 tumor biopsy cobas negative cases, 3 were positive defined by ddPCR. In 23 patients received Osimertinib treatment, the OOR was 60.9%, quantification of T790M after 6 weeks of treatment decreased to very low level, no association was observed between response status and T790M mutation decrease.
Conclusion:
ddPCR is more sensitive in plama ctDNA testing and should be performed even tumor tissue biopsy yielded negative results in certain cases. Osimertinib significantly decreased plasma T790M level, but not associated with clinical response.
