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Tang Feng Lv



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
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      P1.01-006 - Effect of EML-Alk Fusion Variant and Fusion Abundance on the Efficacy of Crizotinib in Non-Small Cell Lung Cancer (ID 8552)

      09:30 - 09:30  |  Presenting Author(s): Tang Feng Lv

      • Abstract

      Background:
      EML4-ALK fusion gene is a molecular subtype of non-small cell lung cancer (NSCLC), which is carcinogenic both in vitro and in vivo. Most of the EML4-ALK-positive NSCLC patients have effectively sensitivity with an ALK tyrosine kinase inhibitor (TKI), such as crizotinib. However, the treatment outcomes and duration of response are heterogeneous. EML4-ALK has several variants. The effects of ALK fusion variants on the efficacy of crizotinib is still unclear, although many scientists are committed to this work. In addition, we also unknown the effects of ALK variants allele fraction (AF) on the efficacy of crizotinib.

      Method:
      Among 54 patients with advanced NSCLC were treated with crizotinib as the first-line or further-line ALK-TKI between 2013 and 2017, eventually, we identified 48 patients whose the tumor samples were detected by IHC(38), FISH(2), NGS(5),PCR(1) and ARMS(2). Through retrospective analysis, we assumed the efficacy of crizotinib on the basis of the PFS according to the ALK variants and its allele fraction.

      Result:
      Among the 29 ALK-positive patients, the most common ALK variants was variant 1 in 13 patients (44.9%), followed by variant 3 in 7 patients (24.1%), variants 2 in 2 patients (6.9%), other variants in 7 patients (24.1%). We divided all variants into two subgroups: V1/3 and V2/others. We found 35.4% of the samples test results between the next generation sequencing (NGS) and hospital immunohistochemical were not concordence. Further analysis found that patients who did not match that PFS were shorter (p=0.036). By the NGS, we observed from the figure that the variant 2/others group, the median PFS had a longer trend than V1/3 group, although not statistically significant（p>0.05. The level of AF was no correlated with PFS (P=0.346).

      Conclusion:
      The above results show that next-generation sequencing (NGS) can identify ALK variants and AF, therefore, NGS can be used as a supplement to a detection method. The type of EML4-ALK fusion variants may has a certain correlation with PFS in patients who oral crizotinib treatment. Since the sample size of this study is small, we have not yielded accurate results and found only these phenomena. We believe that in the near future, most NSCLC patients can be detected by NGS detection of gene mutations, especially EML4-ALK fusion gene, and according the different of the fusion gene variant type which can be estimated the efficacy of the ALK-TKIs, to provide the basis of individualized treatment options for NSCLC patients.

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      P1.01-073 - Over-Expression of GGPPs Contributes to Tumor Metastasis and Correlates with Poor Prognosis of Lung Adenocarcinoma (ID 8473)

      09:30 - 09:30  |  Author(s): Tang Feng Lv

      • Abstract

      Background:
      This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma

      Method:
      GGPPS expression was detected in lung adenocarcinoma tissues by qRT-PCR, tissue microarray (TMA), and western blotting. The relationship between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients was assessed. GGPPS was downregulated in SPCA-1, PC9, and A549 cells, using siRNA, and upregulated in A549 cells, using an adenoviral vector. The biological role of GGPPS in cell proliferation, apoptosis, migration, and invasion was determined by MTT and colony formation assays, flow cytometry, and transwell and wound-healing assays, respectively. In addition, the regulatory role of GGPPS on the expression of several EMT markers was determined

      Result:
      GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Over-expression of GGPPS correlated with patients with large tumors, high TNM stage, lymph node metastasis and poor prognosis. Knockdown of GGPPS inhibited migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E-cadherin, and reduced the expression of N-cadherin and vimentin in lung adenocarcinoma cells

      Conclusion:
      Over-expression of GGPPS correlates with poor prognosis of lung adenocarcinoma, and contributes to metastasis through the regulation of EMT

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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-019 - The Necessity of Contrast-enhanced CT before CT-Guided Percutaneous Transthoracic Needle Biopsy for Lung Lesions (ID 8392)

      09:00 - 09:00  |  Presenting Author(s): Tang Feng Lv

      • Abstract

      Background:
      To evaluate the effect of pre-biopsy contrast-enhanced CT scanning on hemorrhage complicating percutaneous transthoracic needle biopsy

      Method:
      This retrospective study was approved by the institutional review board. We reviewed 1282 biopsy procedures, Chi-square test and multivariate analysis. We conduct propensity score matching by using MatchIt package in R with nearest-neighbor 1-to-1, 2-to-1 and 3-to-1 matching ,respectively

      Result:
      The incidence of pulmonary hemorrhage was 20.2% (259/1282), including 247(19.2%) mild hemorrhage, 7 (0.5%) moderate hemorrhage, and 5 (0.4%) severe hemorrhage. Pre-biopsy CECT scan was significantly associated with pulmonary hemorrhage, and had a positive effect (p=0.008, OR=0.671, 95% CI: 0.499-0.902). When matching hemorrhage and non-hemorrhage cases in proportion of 1 to 1, 1 to 2, and 1 to 3, the correlation of CECT and hemorrhage showed significancy and CECT was indeed a protective factor (p=0.039, 0.028 and 0.013, respectively). Additionally, biopsy position (p=0.016,OR=2.734, 95% CI: 1.207-6.194 for supine, lateral as reference), lesion sizes (p=0.005, OR=0.990, 95% CI: 0.983-0.997), puncture depth (P=0.000, OR=1.017, 95% CI: 1.009-1.025), number of pleural passes (P<0.05, for twice, third, fourth, OR= 1.546, 1.673, 8.746, 95% CI: 1.065-2.244, 1.082-2.588, 2.891-26.456, respectively ) were also related with hemorrhage.

      Conclusion:
      Pre-biopsy contrast-enhanced CT scan is a protective factor for hemorrhage. To reduce the incidence of hemorrhage to the greatest extent. We strongly suggest the patients scheduled to perform percutaneous transthoracic needle biopsy do pre-biopsy contrast-enhanced CT scan routinely.

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    P3.07 - Immunology and Immunotherapy (ID 723)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P3.07-004 - GSDMD Is Required for Effector CD8+ T Cell Responses to Lung Cancer Cell (ID 8461)

      09:30 - 09:30  |  Presenting Author(s): Tang Feng Lv

      • Abstract

      Background:
      Cytotoxic T lymphocytes (CTLs) play a critical role in protection against intracellular pathogens and tumor. To induce target cell death, CTL mainly use two major contact-dependent cytotoxic pathways that are dependent on Fas ligand (FasL) and lytic granules. CTLs eliminate malignantly transformed cells principally by releasing the contents of cytotoxic granules into the immune synapse formed with their target cell. The granule serine proteases, known as granzymes (Gzms), induce apoptosis after they are delivered into the target cell cytoplasm by the pore-forming granule protein perforin. Therefore, we hypothesized that other pore-forming protein, especially those can form pores from within mammalian cells, may be implicated in the target cell killing process of CTL. Since GSDMD is a recently discovered pore-forming protein whose N-terminal domain can insert the inner leaflet of the cell membrane and form extensive pores, we speculate that GSDMD may participate in the CTL attack. GSDMD is a recently discovered pyroptosis executioner in monocyte, whose N-terminal domain can insert the inner leaflet of the cell membrane and form extensive pores. Although the role of GSDMD in the pyroptosis has been clear, the function of GSDMD in other biological system remains elusive. In the present study, we investigated the role of GSDMD during CTL responses to NSCLC cancer cells.

      Method:
      3LL and H1299 cells were cultured in RPMI-1640 (HyClone, USA) supplemented with 10% fetal bovine serum, Ovalbumin-expressing 3LL cells (3LL-OVA) were generated by transfection with a lentiviral plasmids harbouring cytosolic chicken ovalbumin. C57BL/6 mice and TCR-transgenic OT-1 mice. Mouse CD8[+] T cell isolation and stimulation, Human CD8[+] T cell isolation and stimulation, Real-time PCR analysis, Western blot analysis, Immunofluorescence cell staining, Immunohistochemistry, Lentiviral vectors transduction, In vitro cytotoxicity assays, Bioinformatics analysis,

      Result:
      We showed that GSDMD expression was consistently correlated with CD8[+] T cell markers in TCGA cohorts. The expression of GSDMD protein could be detected in the tumor infiltrating lymphocyte. GSDMD cleavage increased both in the OT-1 CTLs and the human activated CD8[+] T cells. Moreover, Colocalization of GSDMD with granzymeB was observed in proximity of immune synapse. GSDMD deficiency reduced the cytolytic capacity of human CD8[+] T cells.

      Conclusion:
      These results identified a previously unknown role of GSDMD in CTL and demonstrated that GSDMD is required for an optimal CTL response to lung cancer cell.