Expression And Significance Of ABCG2，VEGF-C And Cyclin-D1in Human Lung Cancer And Their Relationships

Background: Lung cancer is the first course of death associated with tumorthroughout the world. And the mortality rate of lung cancer ranks first among all thediseases. Lung cancer is the focus of chest imaging. Traditional imaging can onlymanifest the morphological features of lung cancer while the continuous developmentof modern cytology, molecular biology, molecular immunology and the proposing ofthe concept of cancer stem cell provide a new direction for the early diagnosis andtreatment of lung cancer, and the research of the mechanism of tumor recurrence.Besides, the researchers indicate that the stem cells with ability to escape radiotherapyand chemotherapy are the main course leading to tumor recurrence and metastasis.Since Goodell found SP cells(Side population cells) sub-group in the bone marrowand enriched stem cells in the SP sub-group, people have found SP cells sub-group inall kinds of solid tumors and enriched cancer stem cells in the SP cellssub-group.ABCG2ATP-binding cassette transporter gene is one of the specialbiomarkers derived from the hematopoietic stem cells. As the evidences show，the geneis expressed with a high specificity in the non-small cell lung cancer cell lines. AndABCG2has gradually become the candidate gene to isolate the lung cancer stem cellsand apply to targeting therapy after surgery.Previous research has shown that cyclinD is the important regulatory protein ofthe G1/S restriction point during the cell cycle. It plays an important role in promotingcell proliferation and cell cycle entry. Now many subtypes have been found andCyclinD1is one of the subtypes.Some studies have indicated that vascular endothelial growth factor-c (VEGF-C)not only has the ability to promote cancer lymphangiogenesis and angiogenesis, but alsoincreases the affinity of tumor cells for lymph and blood vessels, which can promote theinvasion and metastasis by way of the blood vessels or lymphatics, and offer favourable terms for tumor spread. But it is still not very clear whether VEGF-C contributes to thecharacteristic of certain tumor-specific organ metastasis.Objective: Investigate the expression and significance of ABCG2, VEGF-C andCyclin-D1in the lung squamous cell carcinoma and their relationships between eachother.Method: Lung cancer tissues (all from lung squamous cell carcinoma) wereobtained from50patients (No patients had received chemotherapy or radiotherapybefore bio-autopsy or surgery) by bio-autopsy or surgery. ABCG2, Cyclin-D1, VEGF-Cproteins expression of50lung cancer specimens were analyzed byimmunohistochemistry. Negative controls had the primary antibody eliminated. Humanplacenta tissues were used as positive control. In addition, ten specimens of normal lungtissues were included for comparative study. Use SPSS13.0to count data and analyzethe correlation.Results:1, The present study confirmed the predominant localization of ABCG2transporter in plasma membrane. some of ABCG2-positive tumors showed mixedmembranous and cytoplasmic staining; the predominant localization of CyclinD1transporter mainly distributed in nucleus, and the predominant localization of VEGF-Ctransporter was in the cytoplasm.2, Compared with normal lung tissue, ABCG2, Cyclin-D1, and VEGF-C showhigh expression in lung squamous cell carcinoma, and the positive expression rate ofthem were72%,66%,82%,significantly higher than that of normal lung tissure.3, There was a significant positive correlation between the expression of VEGF-Cand ABCG2in lung squamous cell carcinoma; the same with the expression ofCyclin-D1and ABCG2and the expression of Cyclin-D1and VEGF-C.4, There was closely correlation between the expression of ABCG2and tumordifferentiation and the lymphatic metastasis of the lung cancer, but it had no correlationwith the gender, age, smoking, tumor size and tumor’s clinical stages of the patients; theexpression of the VEGF-C and the CyclinD1were associated with the tumordifferentiation, lymphatic metastasis and clinical stages of the lung cancer, but they hadno relationship with the gender, age, smoking and tumor size of the patients.5, Patients with positive expression of two or more indicators had higher risk oflymph node metastasis, while patients with positive expression of only one indicator orall negative expressions had lower risk of lymph node metastasis. Conclusion: In lung squamous cell carcinoma, ABCG2, VEGF-C, CyclinD1arehighly expressed. They play an important role in development, invasion and metastasisof the lung Squamous Cell Carcinoma. They will become important indicaters to assessthe risk of recurrence and metastasis after surgery and the target of treatment in thefuture.