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Yuqing Lou



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    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.03-05 - Transcriptome Landscape of Lung Adenocarcinoma Patients Revealed Distinct Trajectory Patterns (ID 12025)

      16:45 - 18:00  |  Presenting Author(s): Yuqing Lou

      • Abstract
      • Slides

      Background

      The hallmarks of cancer was proposed to elucidate the common trajectory of tumors of different tissues of origin and genetic makeups, which were expected to attributed to disruption of regulatory pathways conferring survival and growth advantages to tumor tissues. However, the specific biological processes involved in each milestones in the trajectory of development of lung adenocarcinoma, particularly regarding tumor stages, remain elusive. The datasets of The Cancer Genome Atlas (TCGA) project lend potential for discovering the distinctive expressional patterns of differentiated subpopulations, and exploring the dynamic evolution of biological activities within tumor cells.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      RNA sequencing level 3 data of 56 pairs of tissue and adjacent normal samples were obtained from TCGA. Differential expression analysis was conducted using ‘edgeR’ package across the each tumor stage. Differentially expressed genes were derived with fold change>=4 and FDR <= 0.01, followed by KEGG pathway analysis. Odd ratios (ORs) were extracted to indicate the degrees of dysregulation of each pathway.

      4c3880bb027f159e801041b1021e88e8 Result

      After removing non-cancer associated pathways from the 77 pathways identified as dysregulated in those samples, we arrived at 35 pathways. In “Cell cycle” and “Pathways in cancer”, ORs display positive correlation with tumor stages, and the Stage IV showed appreciably higher OR than other stages. Noteworthily, Stage IV has very high Ors in “PPAR signaling pathway”, “Renin-angiotensin system” and “p53 signaling pathway”, which represents canonical pathways implicated in cancer pathologies.

      figure.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      We identified pathways that display correlation with tumor stages, although some deviations are expected to stem from differences in treatment, complicated disease, and health conditions, etc. These results display considerable linear correlation between the degree of dysregulation of cancer pathways, which promise applying RNA sequencing in characterizing the bona fide cell fate of tumor tissues.

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      P1.03-16 - Anlotinib Inhibits Angiogenesis of Refractory Advanced Non-Small Cell Lung Cancer via Blocking CCL2 Expression (ID 12406)

      16:45 - 18:00  |  Author(s): Yuqing Lou

      • Abstract
      • Slides

      Background

      Anlotinib has been demonstrated to be effective in prolonging progression free survival (PFS; Anlotinib: 5.37 months vs Placebo: 1.40 months) and overall survival (OS; Anlotinib: 9.63 months vs Placebo: 6.30 months) of refractory advanced Non-Small Cell Lung Cancer (NSCLC) patients in clinical trials. Clinical evidences suggested that Anlotinib-induced anti-tumor efficacy could be attributed to anti-angiogenesis. However, the underlying molecular mechanisms and predictive biomarker of Anlotinib are still unclear.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      437 patients with advanced NSCLC enrolled in clinical study, and 294 patients received Anlotinib therapy. Retrospectively analysis of the Anlotinib-administrated 294 NSCLC patients was performed to screen out underlying biomarker for Anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the anti-tumor molecular mechanism of Anlotinib in vitro. CCL2 levels and their roles in angiogenesis were evaluated by ELISA detection, RT-qPCR quantification, and immunofluorescence assay, in vivo. Changes in serum CCL2 levels were analyzed to reveal the correlation of Anlotinib response between responders and non-responders.

      4c3880bb027f159e801041b1021e88e8 Result

      Anlotinib therapy is more beneficial to prolong OS for NSCLC patients harboring positive driver gene mutations, especially for patients harboring EGFRT790M mutation. Moreover, our data indicated that Anlotinib-induced cell viability downregulation, cell apoptosis induction, cell invasion inhibition, cell cycle arrest, and cell migration inhibition are associated with CCL2 levels in vitro. We demonstrated that Anlotinib inhibits angiogenesis of NCI-H1975 derived xenografts model via inhibiting CCL2 in vivo. Lastly, we found that Anlotinib-induced serum CCL2 level decreases are associated with the benefits of PFS and OS, in refractory advanced NSCLC patients (n = 28).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study reports a novel anti-angiogenesis mechanism of Anlotinib via inhibiting CCL2 in NCI-H1975 derived xenografts model, and suggests the changes in serum CCL2 levels may be used to monitor and predict clinical outcome in Anlotinib-administered refractory advanced NSCLC patients. The biomarker of serum CCL2 alteration may guide precision therapy of Anlotinib for NSCLC patients at third-line or over third-line.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.03-30 - The Number of Mutated Repair Genes as Predictor for Tumor Mutation Burden of Lung Adenocarcinoma (ID 12027)

      16:45 - 18:00  |  Presenting Author(s): Yuqing Lou

      • Abstract
      • Slides

      Background

      Disruption of repair gene products will result in higher risk of mutation events and genetic instability. Despite some repair genes such as BRCA1 and FANCA being intensively reported in breast cancer, ovarian cancer, and the predisposition to cancers, the effects of protein dysfunction of repair genes on mutation events have not been quantified. The established repair pathways are responsible for different mutation events and may account for respective mutation patterns. Therefore, we conducted an in-depth investigation of effect of individual repair pathways or individual repair genes on tumor mutation burden (TMB).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We obtained level 4 variant datasets from The Cancer Genome Atlas (TCGA) which comprises of 568 samples. The TMB of each individual was calculated and the population was divided into subgroups as per the status of harboring mutations in repair genes as well as the specific repair pathways.

      4c3880bb027f159e801041b1021e88e8 Result

      In the 568 lung adenocarcinoma patients, 434 patients have somatic mutations in any of the 112 DNA repair genes. The individuals harboring mutations in repair genes have significantly higher TMB (Mean=3.019, S.E.=0.206) than those do not (Mean=11.085, S.E.=0.493), and we derived a 3.81-fold increase in TMB for mutations occuring in an additional repair gene. Those that harbor mutations in TP53 account for 63% of the population, and ATM and PRKDC account for 11% and 10, respectively.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      We identified most highly mutated repair genes and quantified the increase in risk for each additional mutated repair gene. Although the TMB of individuals with mutations in specific repair gene or pathway show no significant difference, a larger dataset that comprises adequate number of samples within each explanatory variables such as incidence of cell division, tumor stages to be taken into model, can be expected to derive a more robust predictor.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.11 - Screening and Early Detection (Not CME Accredited Session) (ID 943)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.11-19 - Expression of TNFRII in Serum is Correlated with the Significant Risk of Subcentimeter Lung Adenocarcinoma (ID 12954)

      16:45 - 18:00  |  Author(s): Yuqing Lou

      • Abstract
      • Slides

      Background

      With the rapid advances of low-dose computed tomography (LDCT) screening for lung cancer, the opportunity to detect subcentimeter non-small cell lung cancer (NSCLC) is gradually increasing. The results of many previous studies have shown that even subcentimeter NSCLCs are not always in the early stage. Thus, it is quite important for us to judge the possibility of malignancy for these patients, even the tumor size is less than 10mm. However, subcentimeter lung cancer is hard to diagnose only via biopsy and imaging features because of its tinny size. Chronic inflammation is well established as a hallmark in lung carcinogenesis. In our previous study, B lymphocyte chemoattractant (BLC), is found to be slightly associated with the risk of subcentimeter lung adenocarcinoma. The aim of the present study is to evaluate the correlation between TNF receptor type II (TNFRII) and the risk for subcentimeter lung adenocarcinoma, and the efficacy of diagnosing subcentimeter lung cancer after combining TNFRII and BLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Inflammatory biomarkers were measured in 71 subcentimeter lung adenocarcinoma patients and 71 age-, sex- and smoking-matched healthy controls by using the Luminex bead-based assay.

      4c3880bb027f159e801041b1021e88e8 Result

      The mean (standard deviation or SD) age of patients was 56.01 (8.91) years, and 73.20% of them were female patients (n=52). Never smokers accounted for 85.96% of patients (n=57). The expression level of TNFRII is significantly down-regulated in subcentimeter lung adenocarcinoma patients compared with the healthy controls (P<0.001). And the results were validated by oncomine data mining analysis.

      Elevated levels of TNFRII were associated with an 89% reduced risk for subcentimeter lung adenocarcinoma. (OR=0.11, 95% CI: 0.04-0.30, P=2.4*10-5). BLC was associated with a 2.70-fold (95% CI: 1.31-5.58, P=7.0*10-3) increased risk of subcentimeter lung adenocarcinoma for the comparison of patients in the higher-level group with the lower-level group. To yield more information, the BLC/TNFRII ratio was created to examine their prediction for the risk of subcentimeter lung adenocarcinoma, and as expected there was a 35- fold increased risk for patients in the higher-level group relative to patients in the lower-level group. Further ROC curve analysis revealed that TNFRII was a significant diagnostic biomarker for subcentimeter lung adenocarcinoma, with the area under the curve of 0.73 (95% CI: 0.65-0.82, P=2.0*10-6). The sensitivity, specificity and accuracy were 0.75, 0.72 and 0.73, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings demonstrated that TNFRII was associated with the significant risk of subcentimeter lung adenocarcinoma, and could be a promising biomarker for accessorily diagnosing subcentimeter lung adenocarcinoma.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-37 - The Efficiency of Octamer-4 Specific Cytotoxic T Cells Induce By CD40-B Cells in Killing Lung Cancer Stem-Like Cells (ID 12399)

      16:45 - 18:00  |  Author(s): Yuqing Lou

      • Abstract
      • Slides

      Background

      This study aimed to investigate the correlation of Octamer-4 (OCT4) expression with clinicopathological features and prognosis in lung adenocarcinoma patients, and to further explore the killing effect of OCT4 specific cytotoxic T cells (CTLs) on lung cancer stem cells (LCSCs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      257 lung adenocarcinoma patients underwent thoracic surgery were enrolled in this study and tissue samples were obtained during the operation. OCT4 expression was detected by immunofluorescence staining assay. CD154+ feeder cells were constructed to transfect CD40-B cells, and then mixed with OCT4 antigen peptides and CD8+ T lymphocytes extracted from peripheral blood of lung adenocarcinoma patients, subsequently the OCT4 specific CTLs were co-cultured with PC9 LCSCs to detect the killing efficacy. OCT4+ phenotype was illuminated to be associated with poor differentiation, worse disease free survival (DFS) and overall survival (OS). And Cox’s analysis revealed OCT4+ was an independent predictive factor for shorter DFS and OS.

      4c3880bb027f159e801041b1021e88e8 Result

      CD40-B-cells with antigen presenting capacity was successfully constructed indicated by elevated CD86+, human leukocyte antigens (HLA)-A+ and CD80+ cells percentage, and OCT4 specific CTLs was successfully activated suggested by increased CD3+, CD4+ and CD8+ cells percentage as well as elevated interleukin (IL-2) and interferon (IFN)-γ expressions. OCT4 specific CTLs presented an elevated cytotoxic activity on LCSCs at percentage 75.5% ± 8.2% compared with CMV pp65 CTLs (25.6% ± 5.1%) and blank control CTLs (20% ± 4.7%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, OCT4 expression could be served as a convincing risk biomarker for prognosis in lung adenocarcinoma patients and potential target of CTLs as immuntherapy in killing LCSCs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.12-17 - Prophylactic Cranial Irradiation Can Not Provide Survival Benefits for Resected Small Cell Lung Cancer Without Lymph Node Involvement (ID 13996)

      16:45 - 18:00  |  Author(s): Yuqing Lou

      • Abstract

      Background

      Currently, prophylactic cranial irradiation (PCI) was recommended for all patients after resection small-cell lung cancers, even those without lymph node metastasis. However, there is no directly evidence supporting this recommendation. The purpose of the present study is to assess the role of PCI for this subset of patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively identified completely resected SCLC without lymph node involvement (N0M0) at the Shanghai Chest Hospital between January 2006 and May 2017.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 146 patients (44 patients received PCI, 102 patients did not) were identified in the study. During the observation period, 8.8 % (9/102) patients in the non-PCI-treated cohort and 11.4 % (5/44) patients in the PCI-treated cohort developed brain metastases. There was no significant difference in the risk of cerebral recurrence between the two cohorts with regard to the time to recurrence (P = 0.677). What is more, neither overall survival benefit (HR = 0.88, 95% CI: 0.47–1.65, P = 0.700) nor disease-free survival (HR = 0.95, 95% CI: 0.55–1.62, P = 0.835) was significant between the PCI-treated and non-PCI-treated cohorts.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The present study did not support using PCI in surgically resected small cell lung cancer without lymph node involvement. A relatively lower risk of brain metastasis in this particular subset might explain the inferior efficacy of PCI.

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