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H. Zhong
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-046 - MFN2 Regulates Lung Adenocarcinoma Cell Proliferation and Invasion (ID 2231)
09:30 - 09:30 | Author(s): H. Zhong
- Abstract
Background:
Mitofusin-2 gene (MFN2) encodes a mitochondrial protein which is critical for mitochondrial fusion process. MFN2 was initially identified as a hypertension-associated gene and implicated in the pathogenesis of multiple cancer types. However, roles and underlying mechanisms of MFN2 in lung adenocarcinoma development remain to be determined.
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 effects of MFN2 knockdown on cell proliferation, cell cycle process, cell migration and invasion was investigated in A549 cells. Then MFN2-knockdown induced gene expression changes in A549 cells was analyzed by microarray assay and then functional pathway enrichment analysis was performed to identify critical pathways involved in MFN2-mediated lung adenocarcinoma development. The expression changes of downstream factors were further determined in A549 cells by western blot.
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 (Fig. 1A, B). Furthermore, MFN2 knockdown inhibited cell proliferation (Fig. 1C), induced cell cycle arrest (Fig. 1E) and blocked invasion behavior (Fig. 1D) in A549 lung adenocarcinoma cells. Microarray analysis revealed that a lot of genes were deregulated in A549 cells with MFN2 knockdown (Fig. 1F). Then functional pathway enrichment revealed six pathways were enriched in deregulated genes including Cell cycle, DNA replication, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Chemokine signaling pathway (Fig. 1G). Furthermore, the downregulation of RAP1A and upregulation of RALB and ITGA2 identified in MFN2-knockdown cells by microarray analysis were confirmed by western blot (Fig. 1H).Figure 1
Conclusion:
Our results confirmed the involvement of MFN2 in the pathogenesis of lung adenocarcinoma and revealed that MFN2 was critical for cell proliferation and invasion in lung adenocarcinoma cell line A549. Furthermore, microarray analysis identified multiple pathways deregulated in MFN2-knockdown cells, providing valuable insights about the mechanisms underlying MFN2-associated lung adenocarcinoma development.
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P1.04-090 - Roles of MLF1IP in the Proliferation of Lung Adenocarcinoma Cells (ID 2234)
09:30 - 09:30 | Author(s): H. Zhong
- Abstract
Background:
MLF1IP was initially identified as a MLF1 interacting protein, which encodes a centromere protein essential for cell cycle and mitosis. It has been reported that MLF1IP depletion impaired the interaction between centromere and microtubules, finally inducing defects in cell mitosis. However, the involvement of MLF1IP in lung adenocarcinoma development and related mechanisms remain to be elucidated.
Methods:
MLF1IP expression at mRNA level in 15 pair lung adenocarcinoma/adjacent normal lung samples was examined with real-time PCR assay. Then the expression of MLF1IP in human lung adenocarcinoma cells A549 was inhibited with lentiviral-mediated shRNA strategy. Effects of MLF1IP knockdown on cell proliferation was analyzed by Cellomics cell counting method and MTT assay. Then the impact of MLF1IP knockdown on colony formation, cell cycle process and cell survival was determined in A549 cells by colonogenesis assay, PI staining and Annexin V-APC staining respectively.
Results:
MLF1IP expression was significantly increased in lung adenocarcinomas as compared to adjacent normal lung tissues (fold change=2.50, P<0.05), with higher MLF1IP expression observed in 66.7% (10/15) samples while lower expression observed in only 20% (3/15) samples (Fig. 1A). Furthermore, MLF1IP knockdown impaired cell proliferation (Fig. 1B, C), inhibited colony formation ability (Fig. 1D), induced cell cycle arrest (Fig. 1E) and promoted cell apoptosis (Fig. 1F) in A549 lung adenocarcinoma cells.Figure 1
Conclusion:
Our study showed that MLF1IP expression is correlated with lung adenocarcinoma development and MLF1IP expression is critical for cell proliferation and survival in lung adenocarcinoma cell line A549. MLF1IP represents a novel potential target for lung adenocarcinoma therapy.
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P3.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 211)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.02-004 - PD-L1 Overexpression in NSCLC Inversely Correlated with Survival of NSCLC Patients (ID 1100)
09:30 - 09:30 | Author(s): H. Zhong
- Abstract
Background:
Programmed cell death protein 1, also known as PD1, is a 288 amino acids cell surface protein in the immunoglobulin superfamily. [[1]] PD-1 is expressed on T-cells and pro-B cells, plays a pivotal role in their differentiation. [[2]] PD-1 has two ligands, PD-L1 and PD-L2, which are the members of a peripheral membrane protein family called B7. [[3][4]] PD-L1 can suppress immune system in some special events such as pregnancy and auto immune disease. Binding of PD-L1 with its receptor PD-1 on T cells delivers a signal that inhibits TCR-mediated activation of IL-2 production and T cell proliferation. [[5]] PD-L2’s expression is more restricted compare to PD-L1 and mainly in antigen-presenting cells like Dendritic Cells and microphages. [[4]] Here we report a study of 139 NSCLC patients diagnosed and undergone primary surgery in Shanghai Chest Hospital. The expression of PD-L1 was exanimated by immunohistochemistry, and has a positive correlation with the stage of NSCLC. We also observed a significant correlation between PD-L1 over expression and EGFR mutation, which has the potential to be an favorable prognostic factor. High PD-L1 expression and EGFR mutation also correlated with a significant longer survival time of patients
Methods:
One pathologist examined the H&E- and IHC-stained slides and evaluated the results. The evaluation were done blinded as to the clinical pathologic characteristics and patient outcome. A series of 139 patients diagnosed with NSCLC and undergone primary surgery at Shanghai Chest Hospital (Shanghai, China) from January to December of 2008 were selected in this study. All the patients received lobectomy standard with systematic lymph node dissection. Immunohistochemistry staining for PD-L1 were performed both for tumor and tissue surrounding the tumor.PD-L1 positivity (PDL1+) was defined as 5% tumor cell membrane staining at any intensity.One pathologist examined the H&E- and IHC-stained slides and evaluated the results. The evaluation were done blinded as to the clinical pathologic characteristics and patient outcome. Overall survival data were obtained for each patient by following up visit performed on 2014.
Results:
A total of 139 tumors were examined after exclusion of uninformative slides. There were 72 patients (54.1 %) with stage II, and 61 (45.9 %) with stage III disease. For histological subtypes, there were 90 with adenocarcinoma, 43 with square carcinoma, and 6 with others. Of these, positive evaluation of PD-L1 staining was present in 81 (61.8 %) specimens, while 50 ( 38.2 %) specimens showed negtive/low PD-L1 staining, while the tumor adjacent tissue showed also negtive/low PD-L1 expression .We also did genotyping for the specimens and found about one third of them (50 in a total 133 specimens, 33.3%) carry EGFR mutation. Among the mutations,15 are happened on exome 19 and 33 are on exome 21. PD-L1 positively expression imply a longer survival time compared with PD-L1negatively expression.
Conclusion:
Our results suggest a prognostic value of PD-L1 expression evaluation, which can also be a potentiall immuno-target therapy for lung cancer
