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B. Han



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    Imaging and locally advanced NSCLC (ID 41)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      61PD - Recurrence risk-scoring model for resected stage I lung adenocarcinoma with solid component (ID 326)

      14:45 - 15:45  |  Author(s): B. Han

      • Abstract

      Background:
      The presence of solid histologic pattern in lung adenocarcinoma (ADC) is associated with early recurrence. However, individualized prognosis in patients with solid component is still unclear. This study aimed to develop a nomogram predicting the recurrence probability in stage I lung ADC patients with solid component.

      Methods:
      A total of 5904 patients with stage I lung ADC who underwent curative surgical resection from January 2008 through December 2014 at Shanghai Chest Hospital were retrospectively reviewed. Tumors were subtyped by using the IASCL/ATS/ERS classification. Of these patients, 708 contained a solid component. Prognostic value of gender, age at diagnosis, smoking history, operation type, tumor location, tumor size, pathological subtype, cell differentiation, lymphovascular and visceral pleural invasion were investigated. Multivariate Cox regression analysis of recurrence-free survival (RFS) in patients with solid component was performed and a nomogram to predict RFS was constructed. The nomogram was internally validated.

      Results:
      The overall recurrence rate in patients with solid component was 25.0% (177/708), with predominant solid subtype and minor solid component in 49.2% (87/177) and 50.8% (90/177) of cases, respectively. Larger tumor size (P = 0.002), predominant solid component (P = 0.003), advanced age at diagnosis (P = 0.015), and visceral pleural invasion (P = 0.040) were associated with an increased risk of recurrence and were included in the nomogram. The predictive model had a concordance index of 0.643 (95% confidence interval, 0.601-0.685) and showed good calibration.

      Conclusions:
      The nomogram model including identified risk factors for RFS is applicable in treatment decision-making for early stage lung ADC with pathological solid component. External validation is required to recommend this nomogram in routine practice.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      Shanghai Chest Hospital

      Disclosure:
      All authors have declared no conflicts of interest.

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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 5
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      128P - Serum DKK-1 as a clinical and prognostic factor in non-small cell lung cancer patients with bone metastases (ID 192)

      12:30 - 13:00  |  Author(s): B. Han

      • Abstract

      Background:
      The Wnt/β-catenin pathway plays a crucial role in tumor pathogenesis, specifically in cell proliferation, angiogenesis, motility and invasiveness. The activity of Wnt family ligands is antagonized by several secreted factors including Dickkopf (DKK). A member of the Dickkopf family, DKK-1, is a 35 kDa secreted protein that is a potent inhibitor of Wnt/β-catenin signaling. The study was designed to evaluate the association between serum Dickkopf-1(DKK-1) and non- small cell lung cancer(NSCLC) bone metastases.

      Methods:
      Serum DKK-1and CEA levels were quantified in 318 NSCLC patients, 140 with osseous metastases and 178 with extraosseous metastases. We used receiver operating characteristics (ROC) to evaluate the predictive qualities of these parameters for bone metastases.

      Results:
      Serum DKK-1 levels were significantly higher in patients with osseous metastases compared with patients with extraosseous metastases (P < 0.001). ROC curves showed that the optimum cutoff was 311.8 ng/ml (area under curve [AUC] 0.791, 95% confidence interval [CI] 0.739–0.843, sensitivity 77.1% and specificity 71.4%). ROC analysis also showed that testing both DKK-1 and CEA increased the detection accuracy for NSCLC bone metastases compared with CEA alone (AUC 0.797, 95% CI 0.746–0.848, sensitivity 82.9% and specificity 68.9%; DKK-1 plus CEA vs. DKK-1 alone P = 0.370; DKK-1 plus CEA vs. CEA alone P = 0.0001). Thus, serum DKK-1 correlated with the number of bone lesions (P = 0.042). In osseous metastases group, Kaplan–Meier analysis showed that patients with high serum DKK-1 levels had poorer overall survival than patients with low serum DKK-1 levels (P = 0.025), and multivariable analyses showed serum DKK-1 to be an independent prognostic factor for overall survival (P = 0.029).

      Conclusions:
      Our data shows that serum DKK-1 levels are increased in NSCLC patients with bone metastases. More importantly this is the first report to show that high serum DKK-1 levels are associated with the extent of bone metastases and poor survival in NSCLC patients with bone metastases.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      The Science and Technology Development Fund of Shanghai Chest Hospital (Grant No. 2014YZDC10101)

      Disclosure:
      All authors have declared no conflicts of interest.

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      15P - PLGF regulates crosstalk between non-small cell lung cancer cells and tumor-associated macrophages in cancer vascularization and growth (ID 253)

      12:30 - 13:00  |  Author(s): B. Han

      • Abstract

      Background:
      The growth and invasion of non-small cell lung cancer (NSCLC) require assistance of tumor-associated vascularization, the underlying molecular mechanisms of which remain eluted. Recently, we reported that placental growth factor (PLGF) was expressed by NSCLC cells, and promoted the metastasis of NSCLC cells. Here, we showed that NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through the surface expression of the receptor for PLGF, Flt-1, on macrophages.

      Methods:
      Ten week-old male NOD/SCID mice were used for transplantation of 10[7] AAV-transduced/labeled A549 cells by tail vein injection. Bones from 12-week-old male C57BL/6 mice were flushed with macrophage culture media. Isolated bone-marrow-derived macrophages (10[5]) were co-cultured either with equal number of A549 cells (10[5]) with/without of 10µmol/l SB431542, or with/without recombinant PLGF (100ng), or with/without of 10 µg/l sFlt-1. Two days after co-culture, the changes in A549 cell number were determined with an MTT assay, and the macrophage subtypes were determined by flow cytometry.

      Results:
      In a transwell co-culture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete transforming growth factor β 1 (TGFβ1) to enhance the growth of endothelial cells in a HUVEC assay.

      Conclusions:
      Thus, our studies suggest that the cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFβ receptor signaling may promote the growth and vascularization of NSCLC.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      This work was supported by the National Natural Science foundation of China (81402378).

      Disclosure:
      All authors have declared no conflicts of interest.

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      168P - Clinical and prognostic characteristics of primary pulmonary non-Hodgkin’s lymphoma: A retrospective analysis of 38 cases in a Chinese population (ID 194)

      12:30 - 13:00  |  Author(s): B. Han

      • Abstract

      Background:
      Primary pulmonary non-Hodgkin’s lymphoma(NHL) is very rare, and although the prognosis is favorable, clinical features, beneficial diagnostic procedures, prognostic factors and optimal management have not been clearly defined.

      Methods:
      In this study, thirty-eight cases of primary pulmonary NHL treated in Shanghai Chest Hospital during a 10-year period were retrospectively reviewed, and clinicopathological features and prognosis were analyzed.

      Results:
      There were twenty-eight patients with mucosa-associated lymphoid tissue (MALT) lymphoma, three with diffuse large B-cell lymphoma, one with peripheral T-cell lymphoma, one with mantle cell lymphoma and five with unclassified B-cell lymphoma. The cohort consisted of 21 male and 17 female patients with a median age of 57.5 years. At presentation, 36.8% of patients were asymptomatic, and unilateral tumors occurred more frequently than bilateral and predominantly in the right lung. Thirty-three patients underwent surgical resection single or combination chemotherapy, and five patients received combination chemotherapy alone. Overall survival(OS) was significantly longer in patients with MALT lymphoma than that of non-MALT lymphoma (129.9 vs. 71.5 months, P = 0.019 by log-rank test). Patients who had received surgical resection had a better OS (126 vs. 65.4 months, P = 0.036 by log-rank test). Additionally, multivariate analysis showed that elevated serum lactate dehydrogenase (LDH) level was independently associated with a poor OS (P = 0.048).

      Conclusions:
      Primary pulmonary NHL has atypical clinical manifestations and non-specific imaging changes. Surgical resection is vital in clarifying the diagnosis and obtaining a favorable prognosis. Serum LDH level was an independent prognostic factor.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      Shanghai Chest Hospital

      Disclosure:
      All authors have declared no conflicts of interest.

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      62P - Risk factors associated with early vs late recurrence in stage I lung adenocarcinoma (ID 436)

      12:30 - 13:00  |  Author(s): B. Han

      • Abstract

      Background:
      Patients with stage I lung adenocarcinoma (ADC) develop recurrences after complete surgical resection, both early and over the long term. This study aimed to identify and compare risk factors for early and late recurrence after surgery in stage I lung ADC patients.

      Methods:
      We analyzed recurrences among 5904 patients with stage I lung ADC who underwent curative operations at Shanghai Chest Hospital between January 1, 2008 and December 31, 2014. Recurrences were classified as within 2 years (early), and more than 2 years (late) after surgery. The clinicopathologic findings were compared between patients with early and late recurrences. Both univariate and multivariate analyses were performed, incorporating factors of gender, age at diagnosis, operation type, tumor location and size, pathologic subtype, cell differentiation, lymphovascular invasion, visceral pleural invasion, and smoking history.

      Results:
      Recurrence occurred in totally 628 (10.6%) patients, with early and late recurrence in 300 and 328 patients, respectively. Early and late recurrences shared common risk factors of advanced age at diagnosis (P = 0.013 and P = 0.006, respectively), poorly cell differentiation (both P = 0.000), larger tumor size (both P = 0.000), and visceral pleural invasion (both P = 0.000). Early recurrence was additionally associated with male (HR, 1.327; 95%CI, 1.042-1.690; P = 0.022), sublobar resection (HR, 2.353; 95%CI, 1.634-3.387; P = 0.000), tumor located in the right middle lobe (HR, 1.711; 95%CI, 1.634-3.387; P = 0.005) and solid, micropapillary or variant subtypes (HR, 5.437; 95%CI, 1.258-23.509; P = 0.023).

      Conclusions:
      These findings suggest the existence of different risk factors accounting for early vs late recurrences among patients with stage I lung ADC.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      Shanghai Chest Hospital

      Disclosure:
      All authors have declared no conflicts of interest.

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      9P - Knockdown of MFN2 gene expression inhibits lung adenocarcinoma cell proliferation (ID 254)

      12:30 - 13:00  |  Author(s): B. Han

      • Abstract

      Background:
      Mitofusin-2(MFN2) was initially identified as a hyperplasia suppressor in hyper-proliferative vascular smooth muscle cells of hypertensive rat arteries, which has also been implicated in various cancers. There exists a controversy in whether it is an oncogene or exerting anti-proliferative effect on tumor cells. Our previous cell cycle analysis and MTT assay showed that cell proliferation was inhibited in MFN2 deficient A549 human lung adenocarcinoma cells. MFN2-knockdown induced gene expression changes in A549 cells was analyzed by microarray assay and then functional pathway enrichment analysis revealed that six pathways were enriched in deregulated genes including Cell cycle, DNA replication, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Chemokine signaling pathway, as we previously reported.

      Methods:
      MFN2 expression at protein level was examined in 30 pair lung adenocarcinoma/adjacent normal lung samples with immunohistochemistry staining. Then MFN2 knockdown was performed in human lung adenocarcinoma cells A549 with lentiviral-mediated shRNA strategy. The expression changes of downstream factors were determined in A549 cells by western blot. Furthermore, tumor models in nude mice were generated and tumor formation and progression in these mice were analysed.

      Results:
      As compared to adjacent normal lung tissues, MFN2 expression was significantly higher in lung adenocarcinoma tissues with positive MFN2 signals in 90% (27/30) lung adenocarcinoma tissues and only in 26.7% (8/30) adjacent normal tissues. The downregulation of RAP1A and upregulation of RALB and ITGA2 identified in MFN2-knockdown cells by microarray analysis were confirmed by western blot. In vivo, tumor models in nude mice were generated. Tumor formation and progression in nude mice suggested that MFN2 knockdown reduced tumorigenesis of A549 cells.

      Conclusions:
      The current study confirmed the anti-proliferative effect of MFN2 deficiency and its risk in lung adenocarcinoma.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      This work was supported by the National Natural Science foundation of China (81572249 and 81201839).

      Disclosure:
      All authors have declared no conflicts of interest.