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Q. Zhou
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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Track:
- Presentations: 6
- Moderators:
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
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P033 - A Fusion-Protein Approach Enabling Mammalian Cell Production of Tumor Targeting Protein Domains for Therapeutic Development (ID 171)
00:00 - 00:00 | Author(s): Q. Zhou
- Abstract
Background:
Background: Single chain Fv fragment (scFv) is kind of fusion protein of the variable regions of heavy (VH) and light chains (VL) of immunoglobulins, and it is an important element of chimeric antigen receptors (CARs) for cancer therapy.
Method:
Methods: We sought to produce a panel of 16 extracellular protein domains of tumor markers for use in scFv yeast library screenings. We developed a series of vectors comprising various combinations of expression elements and made GC content optimization of the signal peptide.
Results:
Results: Overall, expression was unpredictable and more than half of the protein domains could not be produced using any of the constructs. Here we described a novel fusion expression system based on mouse TEM7 (tumor endothelial marker 7), which could facilitate protein expression. With this approach we could produce all but one of the tumor marker domains that could not otherwise be expressed. In addition, we demonstrated that the tumor associated antigen hFZD10 produced as a fusion protein with mTEM7 could be used to enrich scFv antibodies from a yeast display library.
Conclusion:
Conclusion: Collectively our study demonstrates the potential of specific fusion proteins enabling mammalian cell production of tumor targeting protein domains for therapeutic development. -
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P039 - Clinical Characteristics and Survival of Patients with Lymphoepithelioma-Like Carcinoma in Lung and Bronchus and Other Sites (ID 159)
00:00 - 00:00 | Author(s): Q. Zhou
- Abstract
Background:
Lymphoepithelioma-like carcinoma (LELC), an unusual histological type of malignancy, occurs in almost all anatomic sites of body including lung and bronchus. Although with strong ties to Epstein-Barr virus infection, LELC at different sites has distinct clinical characteristics. Because of the rarity, it is however largely unclear whether LELC at different sites would lead to different prognosis, independent of clinical characteristics.
Method:
Based on the population-based cancer cohort from the Surveillance, Epidemiology, and End Results database (SEER), we identified all LELC patients from year 1973 to 2015. According to tumor sites, we classified LELC patients into lung and bronchus, nasopharynx, and another eight most common sites. We studied overall survival as the primary outcome, while tumor characteristics as the secondary outcome.
Results:
In total, we identified 2079 LELC patients, of which 86 (4%) were positioned at lung and bronchus and 1208 (58%) at nasopharynx (Figure 1A). Patients with lung and bronchus LELC were older at diagnosis and with more advanced stage, as compared to nasopharyngeal LELC. The 5-year overall survival rates of LELC of lung and bronchus as well as nasopharynx were 35.8% and 59.5% in patients with localized stage (Figure 1B), while 35.1% and 55.5% in patients with regional stage (Figure 1C), respectively. After controlling for tumor characteristics and treatment modes, patients with lung and bronchus LELC were associated with increased risk of overall mortality as compared with LELC of nasopharynx (HR 1.72, 95% CI 1.03 to 2.88).
Conclusion:
The demographics and clinical features of LELC greatly differ by organ of origin. Site may be an important predictor for survival in patients of LELC. Compared with LELC of nasopharynx, pulmonary LELC is associated with worse prognosis, independent of common prognostic factors. -
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P042 - LincRNA00494 Suppresses Non-Small Cell Lung Cancer Cell Proliferation by Regulating SRCIN1 Expression in A ceRNA Manner (ID 182)
00:00 - 00:00 | Author(s): Q. Zhou
- Abstract
Background:
Lung cancer has been recognized as the leading cause of cancer-related deaths throughout the world . Due to failing early diagnosis and severe chemotherapy response, the 5-year survival rate of lung cancer has been staggering at about 15% . Therefore, searching for new biomarkers for metastatic progression of non-small cell lung cancer (NSCLC) is urgent. Recent studies have demonstrated the association between long non-coding RNA (LncRNA) and multiple cancer types. LincRNA00494, a novel long intergenic non-protein coding gene, its function has not been fully expounded. In the present study, we found that LincRNA00494 was down-regulated in non-small cell lung cancer tissue compared with the corresponding adjacent non-tumor tissue. Our findings might reveal the underlying mechanism by which LincRNA00494 aberrant expression conferred NSCLC tumorigenesis.
Method:
We compared the expression level of LINCRNA00494 by RT-PCR in 163 patients with non-small cell lung cancer with the tumor tissue and the normal tissue of distant cancer. We compared the association between LINCRNA00494 and SRCIN1 mRNA in tumor tissues by RT-PCR. Plasmid knockdown and overexpression of LINCRNA00494 were used to compare the effects of changes in LINCRNA00494 expression on SRCIN1 mRNA. To verify the role of miR-150-3p in NSCLC cells, we cloned the 3 -
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P063 - STE029 Overcomes EGFR-TKI Resistance in Human Lung Adenocarcinoma (ID 121)
00:00 - 00:00 | Author(s): Q. Zhou
- Abstract
Background:
STE029 is a novel anticancer drug which consists of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor and novel cancer cell membrane targeting molecular. This study aimed to investigate the effect and mechanism of STE029 on overcoming the EGFR-TKI resistance in NSCLC.
Method:
CCK8 test was used to test the cell viability and survival rate of EGFR mutated PC9 cell (Gefitinib sensitive), PC9/BB4 cell (acquired Gefitinib resistant), and EGFR wild type A549 cell after treatment of STE029, Gefitinib or combination of both. Edu test was applied to detect changes in cell cycle and Hoechst 33258 was applied to detect apoptosis rate in treatment groups. We examined the activity of EGFR/PI3K/Akt, cell cycle and apoptosis signal pathways. In vivo, nude mice were exposed to STE029, Gefitinib and STE029+Gefitinib for 5 weeks, tumor volume was measured, tumor weight was obtained on the last day. P value less than 0.05 would be considered statistically significant.
Results:
PC9 Cells was highly sensitive to Gefitinib , while PC9/BB4 and A549 cell showed significant resistance to Gefitinib treatment, the IC50 of Gefitinib in PC9, PC9/BB4 and A549 cell was 0.12 -
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P084 - Musashi-2 Expression Is an (ID 148)
00:00 - 00:00 | Author(s): Q. Zhou
- Abstract
Background:
Most patients with non-small cell lung cancer (NSCLC) would have local or distant metastases at the time of diagnosis and lose the chance of cure. Currently, there is no reliable biomarker to predict the lymph node metastasis and prognosis of NSCLC. As an RNA-binding protein, the Musashi-2 gene blocks translation by binding to mRNA non-translated region and plays an important role in regulating biological procedures of cell. Existing studies have suggested that Musashi-2 protein associates with the development and poor prognosis of various solid tumors and was reported overexpressed in lung cancer tissue compared with normal lung tissue. Our study aimed to assess the role of Musashi-2 expression in lymph node metastasis and postoperative survival.
Method:
In this present study, immunohistochemistry (IHC) was performed to characterize expression of Musashi-2 protein in NSCLC patients who underwent radical surgeries in our hospital between 2008 and 2013. The expression of Musashi-2 protein in human lung cancer tissues, paracancerous tissues, and metastatic lymph nodes was detected by IHC. The relationship between Musashi-2 protein expression and clinicopathological features, including gender, age, smoking history, pathological type, tumor size, TNM classification, lymph nodes metastasis, and postoperative survival, was analyzed. Kaplan-meier survival analysis and multivariate analysis were used to evaluate the significance of Musashi-2 overexpression as an independent adverse prognostic factor for NSCLC patients received surgery.
Results:
The results revealed that Musashi-2 protein expression was significantly lower in adjacent non-tumor tissues than that in primary lung cancer tissues (P?0.001). The Musashi-2 protein expression was lower in primary lung cancer tissues than that in metastatic lymph nodes (P?0.001). Chi-square test showed that Musashi-2 protein expression was correlated to tumor size (P?0.05), pathological type (P?0.05), tumor stage (P?0.001), and lymph node metastasis (P?0.001), but not to gender, age, smoking history or tumor grade. Kaplan-Meier survival analysis indicated an association of high Musashi-2 protein overexpression with worse postoperative survival in patients with NSCLC (P?0.001). Multivariate COX regression analysis furtherly confirmed that Musashi-2 protein overexpression is an independent predictor for postoperative survival (P?0.001).
Conclusion:
Therefore, Musashi-2 protein overexpression significantly correlates with lymph node metastasis and predicts poorer postoperative survival of NSCLC patients. It may serve as a novel prognostic marker in these patients. -
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P093 - DNA Methylation in CTC And ctDNA is A Promising Marker for Early Detection of Lung Cancer Metastasis (ID 183)
00:00 - 00:00 | Author(s): Q. Zhou
- Abstract
Background:
Lung cancer is the leading cause of cancer-related death worldwide and metastatic dissemination of lung cancer cells represents a significant clinical obstacle to cure the the disease. Aberrant DNA methylation represses gene expression and correlates with cell proliferation, angiogenesis, invasion and metastasis. Many DNA methylation markers have already been used in the early detection of lung cancer. The role of DNA methylation in lung cancer metastasis remains poorly understood and no satisfied marker predicting metastasis were found up to date. We will try to screen out usable methylation markers to improve our diagnosis for metastasis in lung cancer.
Method:
Scientific literature databases were exhaustively searched to retrieve published studies relevant to DNA methylation and NSCLC metastasis. Retrieved studies published in English and Chinese languages were screened according to the stringent predefined inclusion and exclusion criteria, and high quality studies were selected for further analysis. Genes were screened and sorted for further validation.
Results:
A total of 45 published studies were selected in the present analysis. 23 genes or microRNAs were studied in the relationship between methylation and tumor metastasis. The genes include metastatic genes, metastasis suppressor genes , EMT-related genes, microRNAs and noncoding RNA. The methylation rate of these genes and tumor metastasis were studied. Genes with intensive research include P16, Rassf1, DAPK, HOXA5, SOX9, MALAT1 and microRNAs such as mir-182, mir-139. mir-224. No further studies were regarded in the prediction value of these markers in serum and CTC in lung cancer metastasis. These markers might be validated in metastasis prediction in further studies.
Conclusion:
Our analysis results reveal that methylation might be associated with tumor metastasis and poor prognosis in NSCLC patients, and might be good markers in liquid biopsy for early detection of lung cancer metastasis.
