Clinical Features Of Bronchioloalveolar Carcinoma And Preliminary Study Of MicroRNA Related To Metastasis Of Lung Cancer

Part1:Preliminary Study in Clinical Features of Bronchioloalveolar CarcinomaObjective:The incidence of bronchioloalveolar carcinoma (BAC) has risen steadily over the last decades along with the increasing frequency of adenocarcinomas. The objective of our study was to retrospectively review the clinical features of bronchiloloalveolar carcinoma.Methods:160 patients of BAC who were adimitted to Chinse PLA General Hospital from January 2003 to December 2007, were used to analyze the clinical features. The baseline characteristics, clinical symptoms, misdiagnosis, diagnosis methods, TNM stage, pathologic types and imaging types were assessed. For 136 patients with complete clinical data, we performed survival analysis by SPSS 13.0.Results:160 patients were identified for this retrospective practice review.1. Male/Female ratio:1.08:1; Age range:28.30～76.70, the average age:57.28; Smoker/Non-smoker ratio:1:2.33.2. Due to lacking of specific clinical symptoms, BAC were often misdiagnosed. In our study,73 cases (45.6%) were diagnosed based on physical examination and 70 cases (43.7%) were misdiagnosed.3. Postoperative pathologic diagnosis was the most common diagnosis method.4.63 cases were phasel and 27 cases were phaseⅡ.5. Consolidation type and single nodular type were the most common chest CT imaging types.6. For 136 cases with survival analysis, survival rates of 1-year,2- year,3-year,4-year,5-year were 88%,76%,69%,55% and 50%, repectively; 7. Single factor regression analysis showed that smoking history, clinical stage, imaging type, molecular targeted therapy affected the prognosis of patients.8. COX regression analysis results showed that smoking history, history of targeted therapy and TNM stage were independent factors affecting the long-term survival of the patients. After adjusting the other two factors,the mortality risk of smoking patients was 2.555 times of non-smokers, while the mortality risk of non-targeted therapy patients was 2.377 times of targeted therapy patients. Each additional tumor stage would increase the mortality risk by 1.977-fold.Conclusions:1.BAC patients were lack of distinct clinical features and were along with diversity of imaging, so they were tended to be misdiagnosed. Bronchorhea was not commonly seen in BAC.2.BAC progressed relatively slowly,so most of them were diagnosised at earlier stages, with good surgical opportunities. Surgery should be the first therapeutic option, combined with comprehensive treatment of chemotherapy, radiotherapy and molecular targeted therapy. The prognosis of BAC was better than that of other NSCLC. Molecular targeted therapy to BAC showed better efficacy and tolerance.Part 2:Preliminary Study of microRNA Related to Metastasis of Lung CancerObjective:By comparing microRNA expression of lung cancer cells 95D and 95C, we found out microRNAs related to metastasis of lung cancer and predicted target genes of them, which are necessary for the further study of mechanism and signal pathways regulated by the miRNAs.Methods:Microarray was used to find out different microRNAs between 95D and 95C. Then,qRT-PCR was then used to confirm the results. Finally, we predicted target genes of these microRNAs by searching in several famous target genes prediction website.Results:1. The microRNAs associated with metastasis of lung cancer were hsa-miR-7, hsa-miR-29a, hsa-miR-29b, hsa-miR-26b, hsa-miR-30c, hsa-miR-25 and hsa-miR-222.2. EGFR, PAK1, RAFland MMP20 were the predicted target genes of hsa-miR-7.3. DNMT3A/DNMT3B, SPARC, CDC42, VEGFA, IGF1 were the predicted target genes of hsa-miR-29 (hsa-miR-29a,hsa-miR-29b).4. ZEB2, MAPK1 and HGF, MAPK1 and DNMT3A, MMP1 and ZEB2 were the predicted target genes of hsa-miR-25,hsa-miR-26b,hsa-miR-30c,hsa-miR-222, respectively.Conclusion:1. It has been confirmed that hsa-miR-7 prevented metastasis of lung cancer by repressing the expression of EGFR. At the same time,hsa-miR-7 may prevent metastasis of lung cancer by regulating PAK1,RAF1 and MMP20. We need to confirm that and discover the mechanism and signal pathway.2. Abroad studies have confirmed that in non-small cell lung cancer, hsa-miR-29 through regulating DNMT3A/DNMT3B, made abnormal methylation silence tumor-suppressor genes to express, thus inhibiting tumor proliferation and metastasis. Our study showed that hsa-miR-29 may also downregulate the expression of SPARC,VEGFA and IGF1, which repressed the metastasis of lung cancer. The regulating mechanism and signal pathway were needed to be furtherly studied.3. Hsa-miR-25,hsa-miR-26b,hsa-miR-222,hsa-miR-30c may prevent the metastasis of lung cancer by regulating ZEB2,MAPK1 and HGF,MMP1 and ZEB2,MAPK1andDNMT3A, respectively. Further researches are needed to confirm it.