Analysis on risk factors of lung cancer complicated with pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PE) is a potentially fatal complication and its morbidity together with fatalness will further increase when in patients with malignant tumors. Fast and accurate early diagnosis of PE thus seems considerably important. OBJECTIVE: To explore the risk factors of lung cancer complicated with PE. MATERIALS AND METHODS: A retrospective cohort study consisted of 40 lung cancer patients with PE (PE group) and 60 lung cancer patients without PE (non-PE group) were analyzed. RESULTS: The white blood cell (WBC) count, D-dimer and low-density lipoprotein (LDL) were higher in PE group than those in non-PE group (P < 0.05), whereas the arterial partial pressure of oxygen (PaO2 ) in PE group was lower than that in non-PE group (P < 0.05). Carcinoembryonic antigen (CEA) level between two groups also exhibited statistical difference (P < 0.05). Those lung adenocarcinoma patients with stages III and IV tumor, coupled with deep venous thrombosis (DVT), having experienced bevacizumab treatment or platinum-based chemotherapy more likely suffered from PE (P < 0.05). The multivariate analysis revealed that high D-dimer, chemotherapy, DVT, stages III to IV, adenocarcinoma were independent risk factors associated with PE (P < 0.05). The overall survival time of patients in case group was significantly shorter than that in the control group with a median survival duration being 10.5 months (95%CI, 8.95-12.05) and 16.8 months (95%CI, 14.62-18.98), respectively, (P < 0.01). CONCLUSIONS: High D-dimer, chemotherapy, DVT, stages III to IV and adenocarcinoma might have a positive correlation with PE, meanwhile, PE always predicted a poor prognosis in lung cancer patients.

Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line.

Lung cancer is the leading cause of malignancy-related death worldwide, and metastasis always results in a poor prognosis. However, therapeutic progress is hampered by a deficiency of appropriate pre-clinical metastatic models. To bridge this experimental gap, we developed an in vivo metastatic model via subcutaneous (s.c.) injection. The original cell line (XL-2) adopted in this model was newly isolated from the ascites of a patient with extensive metastases of lung adenocarcinoma, thereby avoiding any alteration of its initial molecular biology features from artificial serial cultivation. After comprehensive phenotypical and histological analysis, it was identified as a lung adenocarcinoma cell line. Additionally, the drug test showed that XL-2 cell line was sensitive to docetaxel, and resistant to doxorubicin, indicating it might serve as a cell line model of drug resistance for identifying mechanisms of tumors resistant to doxorubicin. Through this s.c. model, we further obtained a highly metastatic cell line (designated XL-2sci). The metastatic rate of mice in XL-2 group was 3/10, in contrast to the rate of 9/10 in XL-2sci group. Optical imaging, micro-computed tomography (micro-CT) scanning and Transwell assays were further applied to identify the enhanced metastatic capacity of Xl-2sci cells both in vivo and in vitro. Compared with XL-2 cells, ITRAQ labeled proteomics profiling study showed that some tumor metastasis-associated proteins were upregulated in XL-2sci cells, which also indicated the reliability of our model. Proliferation ability of XL-2 and XL-2sci were also evaluated. Results showed that highly metastatic XL-2sci possessed a decreased proliferation capacity versus XL-2, which demonstrated that its increased metastatic activity was not facilitated by a faster growth rate. In conclusion, we successfully developed an in vivo metastatic model using a newly established lung adenocarcinoma cell line, which will be beneficial to further investigations of lung cancer metastasis and to the development of anti-metastasis drugs.

Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC.

To discover metastasis-associated proteins within cancer cells, we used the isobaric tags for relative and absolute quantitation (iTRAQ) approach combined with nano liquid chromatography-tandem mass spectrometry (NanoLC-MS/MS) analysis to identify proteins that were differentially expressed between lung adenocarcinoma cancer cell lines SPC-A-1sci cells with high metastatic potential and parent SPC-A-1 cells with low metastatic potential. By employing biological and technical replicates, we identified 5818 nonredundant proteins and quantified 5443 proteins, 256 of which were differentially expressed in the two cell lines. Through si-RNA-mediated functional screens, Myosin heavy chain 9 (MYH9) and Copine III (CPNE3) were indicated as positively correlating with the migration and invasion properties of SPC-A1sci cells, and the same function of CPNE3 was confirmed in another lung cancer cell line, H1299. Furthermore, overexpressing CPNE3 promoted nonsmall-cell lung cancer (NSCLC) cell line (SPC-A-1 and XL-2) migration and invasion in vitro. Moreover, the targeted knock-down of CPNE3 inhibited the in vivo metastatic abilities of H1299 cells in mouse models. Lastly, immunohistochemistry revealed that the CPNE3 expression level was positively correlated with the clinical stage and TNM classification in NSCLC patients. Taken together, our results indicate that CPNE3 could play a critical role in NSCLC metastasis.