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Sen Yang



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    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA03.02 - Genetic Variants in ERAP1 and NCF2 in the MHC Class I Related Genes Are Associated with Non-Small Cell Lung Cancer Survival (Now Available) (ID 1491)

      10:30 - 12:00  |  Presenting Author(s): Sen Yang

      • Abstract
      • Presentation
      • Slides

      Background

      Adaptive immunity, particularly the presence of tumor-infiltrating CD8+ T cells, is crucial in the control of tumor cells and preventing overall cancer progression. However, the process of CD8+ T cells recognizing and killing tumor cells depends on the expression of MHC class I (MHCI) complex presented on tumor cell surface.

      Method

      In the present study, we performed a two-phase analysis of two independently published genome-wide association studies (GWASs) to evaluate associations between genetic variants in the MHCI-related gene-set and overall survival (OS) of patients with non-small cell lung cancer (NSCLC). In the discovery GWAS dataset, we performed multivariate Cox proportional hazards regression with Bayesian false-discovery probability for multiple test corrections and evaluated associations between 9,718 single-nucleotide polymorphisms (SNPs) in 102 genes and survival of 1,185 NSCLC patients. After validation in another GWAS dataset, we performed linkage disequilibrium, function prediction and a multivariate stepwise Cox proportional hazards regression analysis.

      Result

      We found that two independent, potentially functional SNPs in two genes (ERAP1 rs469783 T>C and NCF2 rs10911362 C>T) were significantly associated with NSCLC survival, and their meta‐analysis showed an adjusted hazards ratio (HR) of 0.83 [95% confidence interval (CI) =0.77–0.89] and P meta =  8.2×10-7; 1.31 (1.06-1.73) and P meta = 0.0009; respectively. A genetic score of unfavorable genotypes of these two SNPs revealed a decreased OS in a dose–response manner (P trend < 0.0001). Further expression quantitative trait loci (eQTL) analysis showed significant associations between the genotypes and mRNA expression levels. Furthermore, the expression levels of these genes in tumor and normal tissues were different and had an effect on patient survival as well.pdf转图片- 老版.jpgpdf转图片- 老版11.jpg

      Conclusion

      Taken together, the genetic variant of the ERAP1 rs469783 and NCF2 rs10911362 from the MHCI pathway genes may be a promising predictor of survival in NSCLC patients via ERAP1 and NCF2 expression alteration.

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    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
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      P1.01-33 - Genetic Variants in FIG4 and IGF1R in the Endosome-Related Genes Are Associated with Non-Small Cell Lung Cancer Survival (ID 1483)

      09:45 - 18:00  |  Author(s): Sen Yang

      • Abstract

      Background

      The endosome is a membrane-bound organ inside most eukaryotic cells and is known to play an important role in the adaptive immunity of mammals. The endocytosed antigens in the antigen presenting cells are delivered to both MHC class I and MHC class II pathways via the endosome.

      Method

      In the present study, we performed a two-phase analysis of two independently published genome-wide association studies (GWASs) to evaluate associations between genetic variants in the endosome-related gene-set and overall survival (OS) of patients with non-small cell lung cancer (NSCLC). In the discovery GWAS dataset, we performed multivariate Cox proportional hazards regression with Bayesian false-discovery probability ( 0.80) for multiple testing corrections and evaluated associations between 49,179 (3,735 genotyped and 45,444 imputed) single-nucleotide polymorphisms (SNPs) in 256 genes and survival of 1,185 NSCLC patients. After further validation in the Harvard Lung Cancer Susceptibility study, we performed linkage disequilibrium, functional prediction and a multivariate stepwise Cox model.

      Result

      We found that two independent, potentially functional SNPs in two genes (FIG4 rs6899506 C>A and IGF1R rs3743254 C>T) were significantly associated with NSCLC survival, and their meta‐analysis showed an adjusted hazards ratio (HR) of 1.16 [95% confidence interval (CI) =1.06–1.26, Pm = 0.001] and 0.78 (0.67-0.91, Pm = 0.002); respectively. A genetic score of unfavorable genotypes of these two SNPs revealed a decreased OS in a dose–response manner (P trend = 0.007). Further expression quantitative trait loci (eQTL) analysis showed significant associations between the genotypes and mRNA expression levels. It was found that the survival-associated FIG4 rs6899506C allele, but not the IGF1R rs3743254T allele, was significantlpdf转图片- 老版.jpgy associated with decreased mRNA expression levels of FIG4 in 373 lymphoblastoid cell lines.

      Conclusion

      Taken together, the genetic variant of the FIG4 rs6899506A allele and IGF1R rs3743254T allele from the endosome pathway genes may be a promising predictor of survival in NSCLC patients via FIG4 and IGF1R expression alteration.

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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-54 - Previous Therapy Strategy Impact on Efficiency of Anlotinib Hydrochloride as 3rd Line Treatment: A Subgroup Analysis of ALTER0303 Trial (Now Available) (ID 1078)

      09:45 - 18:00  |  Presenting Author(s): Sen Yang

      • Abstract
      • Slides

      Background

      Lung cancer remained one of the deadest cancers throughout worldwide. ALTER0303 trial revealed anlotinib might be used as a third-line or further treatment in non-small-cell lung cancer patients. While previous therapy strategy would have impact on efficiency of anlotinib still remained unknown.

      Method

      The subgroup of patients in ALTER0303 were analyzed by using Kaplan-meier estimates, Pearson X2 or Fisher exact test.

      Result

      There is no statistical significance on progression-free survival (PFS) and overall survival (OS) among patients in different previous antiangiogenic treatments groups. Patients in the chest radiotherapy (CRT) group had longer median PFS than non-CRT group (5.93m vs. 4.63m, P=0.027). No matter what kind of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) and chemotherapy regimens used previously, all patients gained longer PFS from anlotinib. While only patients treated with vinorelbine/platinum in EGFR wild type group, pemetrexed/platinum, vinorelbine/platinum and gefitinibin in EGFR mutation group, EGFR TKI used as the first line group could benefit from anlotinib on OS. When the OS was calculated from the time of diagnosis to death, anlotinib may improve about 6 months median OS (33.8m vs.27.8m, P<0.001) compared to placebo with HR (95%CI): 0.77 (0.60, 1.00).figure 1.jpgfigure 2.jpg

      Conclusion

      This study indicated previous bevacizumab or endostatin treatments had no impact on the efficiency of anlotinib. Patients with CRT history benefited more from anlotinib on PFS. EGFR TKI and chemotherapy treatments history had more impact on OS than PFS in patients treated with anlotinib compare to placebo.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-42 - ALK-Rearrangement May Promote VTE by Increasing the Expression of TF in Advanced Lung Adenocarcinoma (Now Available) (ID 1075)

      10:15 - 18:15  |  Presenting Author(s): Sen Yang

      • Abstract
      • Slides

      Background

      Patients with lung cancer are at an increased risk for venous thromboembolism (VTE). About 8% to 15% of patients with advanced none small-cell lung cancer (NSCLC) experience a VTE throughout the course of the disease. However, the incidences of VTE in different molecular subtypes of NSCLC are rarely reported though they have big differentiation in clinical feature and prognosis. Tissue Factor (TF) expressed in many solid tumors could trigger the downstream coagulation cascade and lead to thrombin generation and clot formation.

      Method

      Here we extracted retrospective data from electronic medical records at Henan Cancer Hospital in China between January 2015 and January 2017. Advanced lung adenocarcinoma patients with ALK-rearranged, EGFR mutation and both negative were classified. The incidence of VTE of these patients were calculated. Then we randomly selected ALK-rearranged positive and negative lung adenocarcinoma tissues (N = 29, N = 26, respectively) and detected TF protein expression of the tissues with immunohistochemistry.

      Result

      The present study work flow in shown in Figure 1. At a median follow-up of 2.5 years, 5.85% (30 in 513) patients with advanced lung adenocarcinoma experienced VTE. ALK-rearranged patients (Figure 2A) were more likely to occur VTE than EGFR mutation and both negative patients (Figure 2C) (6 in 29, 20.69%; 11 in 218, 5.05%; 13 in 266, 4.89%, respectively P=0.018). In ALK-rearranged positive tissues, 41.67% (10 in 24) of them had a high expression of TF protein (Figure 2B) – the incidence was significantly higher than that of ALK-negative tissues’ TF protein expression (11.54%, 3 in 26, P=0.015) (Figure 2D). figure 1.jpgfigure 2.jpg

      Conclusion

      ALK positive NSCLC patients are more likely to occur VTE and this might be due to higher expression of TF in tumor tissues.

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