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Yang Wo



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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-03 - Immune Cell Filtration as a Biomarker for the Diagnosis and Prognosis of Lung Adenocarcinoma (Now Available) (ID 2243)

      08:00 - 18:00  |  Presenting Author(s): Yang Wo

      • Abstract
      • Slides

      Background

      Since tumor-infiltrating immune cells provides meaningfully information of prognosis in lung adenocarcinoma, we aimed to construct a novel prognostic immune model on the basis of a systematic assessment of the immune landscape calculated from cancer transcriptomes of lung adenocarcinoma patients.

      Method

      We used an advanced algorithm, which named “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)”, to estimate the 22 immune cell types from public datasets. The selection operator model and least absolute shrinkage and random forest method were then applied to develop immune scores for tumor diagnosis and prognosis.

      Result

      355 lung adenocarcinoma patients and 204 normal controls were obtained to develop a diagnostic model and the diagnostic immune risk score (dIRS) suggested high sensitivity and specificity in both the training sets (AUC= 0.93, P<0.01) and validation sets (AUC=0.89). A prognostic immune score (pIRS) was also established and served as an independent prognostic factor for overall-free survival, which showed better prognostic value than TNM stage. Additionally, by integrating the pIRS with clinical information in a complete nomogram, the result suggested higher accuracy of recurrence risk prediction with well-calibrated curves.

      Conclusion

      In summary, we studied the potential application of immune cells in cancer diagnosis, prognosis and treatment. The proposed diagnostic and prognostic model (dIRS and pIRS) might provide integrative and meaningful signatures for precision medicine and personal management of lung adenocarcinoma patients.

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    MA05 - Update on Clinical Trials and Treatments (ID 123)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA05.02 - Log Odds of Positive Lymph Nodes Predicts Overall Survival and the Benefit of Postoperative Radiotherapy in Malignant Pleural Mesothelioma (Now Available) (ID 1059)

      13:30 - 15:00  |  Presenting Author(s): Yang Wo

      • Abstract
      • Presentation
      • Slides

      Background

      Nodal categories of malignant pleural mesothelioma (MPM) are mostly adopted from lung cancer staging criteria and the N descriptors in the eighth edition of TNM staging system have not been fully verified. We aimed to evaluate the effectiveness of the current N descriptors and a novel prognosticator—the log odds of positive lymph nodes (LODDS)—in predicting overall survival (OS) and postoperative radiotherapy (PORT) benefit in MPM.

      Method

      Patients in the Surveillance, Epidemiology, and End Results (SEER) database with MPM undergoing surgery and lymph nodes examination were extracted and restaged according to the 8th edition TNM staging system. LODDS was calculated as loge[(positive nodes count+0.5)/(negative nodes count+0.5)]. X-tile software determined the optimal cut-point for LODDS. Log-rank tests along with Cox regression analyses were adopted for survival analyses. Harrell's C-index statistic measured discriminatory ability and prognostic performance.

      Result

      A total of 534 patients were enrolled in this study. N descriptors were unevenly distributed. Most cases were staged as N0 (51.9%) and N1 (47.0%), with only 1.1% staged as N2. The eighth edition N descriptors failed to clarify the survival difference between adjacent categories and were incapable of predicting PORT benefit. The cut-points for LODDS were classified as follows: LODDS1 (≤-2.61), LODDS2 (-2.56≤LODDS≤0.62), and LODDS3 (≥0.87). The median survival of LODDS1 was 23.1 months compared with 17.9 months (HR=1.397, P=0.005) and 13.0 months (HR=2.317, P<0.001) for LODDS2 and LODDS3, respectively. The survival curves stratified by LODDS separated nicely without overlapping and the benefit of PORT was limited to cases with LODDS3 (≥0.87). LODDS also provided better C-index than the conventional N descriptors.

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      Conclusion

      LODDS performs better than N descriptors for predicting survival and benefits of PORT in resected MPM, and it could be considered as a potential parameter to compensate for defects in the 8th AJCC TNM staging for MPM.

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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
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-128 - Choice of Postoperative Radiotherapy for Resected IIIA-N2 Non-Small Cell Lung Cancer: Impact of Log Odds of Positive Lymph Nodes (Now Available) (ID 1342)

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

      • Abstract
      • Slides

      Background

      Surgical resection alone results in poor survival in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) owing to high incidence of locoregional recurrence and distant metastasis. One possible way to improve surgical outcome is the administration of postoperative radiotherapy (PORT). However, the benefit and indication of administrating PORT remains controversial for stage IIIA-N2 NSCLC. We aimed to assess log odds of positive lymph nodes (LODDS) as a predictor of the benefit of PORT.

      Method

      Patients with resected stage IIIA-N2 NSCLC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. LODDS was defined as loge[(metastatic nodes count+0.5)/(negative nodes count+0.5)]. X-tile software determined the optimal cut-points for LODDS based on minimal p value method. Survival analyses were conducted with log-rank tests and Cox proportional hazard models.

      Result

      Among patients enrolled in this study (n=4197), 1630 (38.8%) received PORT. LODDS was categorized into four groups: LODDS1 (LODDS≤-1.61), LODDS2 (-1.58≤LODDS≤-0.85), LODDS3 (-0.83≤LODDS≤0.00), and LODDS4 (LODDS≥0.01). The median survival in LODDS group 1, 2 ,3, and 4 was 53, 44, 35, and 25 months, respectively. PORT conferred significant improved survival for stage IIIA-N2 NSCLC. According to multivariate Cox regression analyses, PORT and LODDS were both identified as independent prognostic factors. When analyzed by LODDS group, the benefit of PORT was limited to patients with LODDS4 (LODDS≥0.01), whereas the PORT benefit was not observed in LODDS1-3.

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      Conclusion

      Our study validates LODDS as a significant prognostic factor in stage IIIA-N2 NSCLC. It is worth noting that LODDS may predict which group of patients could benefit from PORT.

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    P1.11 - Screening and Early Detection (ID 177)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.11-20 - Identification of a Thirteen-Gene Prognostic Signature for Lung Adenocarcinoma (Now Available) (ID 2213)

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

      • Abstract
      • Slides

      Background

      The incidence of lung adenocarcinoma has gradually surpassed that of lung squamous cell carcinoma. It is especially important for the diagnosis and treatment of lung adenocarcinoma. Therefore, we used the GEO and TCGA databases to assess the integration of several gene signatures and clinical stages associated with survival.

      Method

      RNA sequencing was performed on LUAD-affected tissues and paired with non-cancerous tissue samples, and the intersection of differentially expressed genes was obtained using the Gene Expression Omnibus datasets GSE117370 and GSE19188, and a protein-protein interaction network was constructed to obtain the hub genes. Then corresponding overall survival information of LUAD patients from The Cancer Genome Atlas project-LUAD were included in the present study. An analysis of the Kyoto Encyclopedia of Genes and Genomes database and Gene Ontology were carried out to study the signature mechanism.

      Result

      In this study, we identified thirteen candidate genes (SPP1, SMAD6, NUF2, NEK2, MMP1, KRT6A, HMMR, GJB2, FAM83A, DEPDC1, COL11A1, CENPF, CCNB1) closely related to survival in LUAD. A linear prognostic model of the eight genes was constructed and weighted by the regression coefficient (β) from the multivariate Cox regression analysis of The Cancer Genome Atlas-LUAD cohort to divide patients into low- and high-risk groups. The prognostic ability of the signature was validated in LUAD patients at our hospital. Patients assigned to the high-risk group exhibited poor overall survival compared to patients in the low-risk group. Finally, functional enrichment analysis showed that cell division played a vital role in the development of LUAD.

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      Conclusion

      Our results highlighted a mRNA signature including thirteen genes, which may serve as a potential prognostic marker of LUAD.

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    P2.12 - Small Cell Lung Cancer/NET (ID 180)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.12-25 - Surgical Management of Pulmonary Carcinoid ≤3cm: Extent of Resection and Lymph Nodes Examination (Now Available) (ID 1778)

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

      • Abstract
      • Slides

      Background

      Early stage lung cancer is being detected at a higher frequency with the development of advanced screening programs. We aimed to investigate the optimal surgical approach in pulmonary carcinoid ≤3cm.

      Method

      Patients with microscopically confirmed pulmonary carcinoid tumors ≤3cm were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2015. Cancer specific survival (CSS), defined as the survival time from cancer diagnosis to death specific to cancer-related death, was the primary outcome variable. Survival curves were plotted with Kaplan-Meier analysis and the difference in survival was estimated by log-rank tests. Multivariate Cox regression methods determined the independent prognostic factors after adjusting for other confounding factors.

      Result

      A total of 2986 patients were included in this study, which comprised 2785 typical carcinoids (TC) and 201 atypical carcinoids (AC). AC histology was associated with larger tumor size and increased risk of nodal metastasis. Lobectomy was performed for bigger carcinoid and correlated with more resected lymph nodes. Sublobectomy was noninferior to lobectomy with regards to CSS. Although lymph nodes involvement conferred significantly decreased survival, lymph nodes resection did not improve survival in either typical or atypical carcinoids.

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      Conclusion

      For patients with T1-sized pulmonary carcinoids, sublobar resection results in similar survival rate compared with lobectomy. Lymph nodes examination did not independently predict survival.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-31 - Melatonin Inhibits Proliferation and Invasion Through Downregulating CircRNA NID1 in Non-Small Cell Lung Cancer Cells (Now Available) (ID 2181)

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

      • Abstract
      • Slides

      Background

      Melatonin could product anti-cancer effects via several mechanisms, including by induction of apoptosis. In this way, it has been shown to be of use, in combination with chemoradiotherapy, for cancer treatment. More and more circular RNAs (circRNAs) revealed to play a critical role in the initiation and progression of cancer, however, the effects of circRNAs on non-small cell lung cancer (NSCLC) remain largely undetermined. The study described here has evaluated effects of melatonin on dysregulated circRNAs and how to affect cell viability, proliferation and apoptosis in human lung adenocarcinoma cell lines (A549, H1299, and H460), which previously had only limited data.

      Method

      The dysregulated circular RNA after melatonin treatment was examined. Cells were treated with melatonin alone at 1 nM, 1 μM and 100 μM concentration for 0, 12, 24, 48 and 72 h in culture. Cytotoxicity was measured by CCK-8 assay. Apoptosis induction was detected by annexin V/PI staining using flow cytometric analysis and DAPI nuclear staining. Transwell assay was used to detect the invasion of lung adenocarcinoma cell lines after treating. Western blot for detection of protein levels regulated by circular RNA.

      Result

      In the present study, we screened the dysregulated circRNAs in human lung adenocarcinoma cell lines after treating and identified circRNA NID1 was to be significantly up-regulated in NSCLC and demonstrated it promotes NSCLC progression in vitro and in vivo. Then, we revealed the expression of miR-16-5p, a downstream factor of circRNA, was significantly down-regulated in NSCLC and acted as a tumor inhibitor, Yes-associated protein 1 was examined up-regulated in cancer and associated with proliferation.

      Conclusion

      Our results highlighted circRNA NID1 promoted NSCLC cell proliferation, invasion, and migration by increasing Yap1 expressions through direct inhibition of miR-16-5p, which may serve as a potential prognostic marker of LUAD.

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