A Study On DNA Copy Number Alterations Related To Metastasis In Lung Squamous Cell Carcinomas

Background:It has been considering that the survival of the patients with lung cancer depends upon staging of the disease.Lymph node status has played an important role in predicting stage and progression of lung cancer.Most patients suffering from lung cancer die from metastasis.However,there are no powerful cancer metastasis related molecular biomarkers used in clinical yet. Histopathologicaily,squamous cell carcinoma is the major type of lung cancers.The objective of this study was to identify a cluster of gain/loss genes from the profile of DNA copy number aberrations in lung squamous cell carcinoma(LSCC) as candidate tumor markers for the human lung cancer lymph node metastasis.Methods: Surgical resected specimens form 18 patients with lung squamous cell carcinoma were studied.According to lymph node status,18 cases were divided into two groups. Patients in low-risk group had no lymph node metastasis during operation and survival in four years while patients in high-risk group had lymph node metastasis when operation and died during two years.The genomic DNA fragments isolated from formalin-fixed and paraffin-embedded tumor tissues were hybridized to Agilent CGH microarray.Results:Many chromosome mutations were happened in our research including many large scale changes and small scale changes.The copy number change in large scale include deletions of 3p,4p,4q,5q,9p,13q,18q and gains of 3q,16p,16q, 17q,19p,19q,22q,while the small scale change including loss of 1p12-34.2, 3p12.1-12.3,8p22-23.2,12q21.31-21.33,18q12.3-22.3,21q1.1-21.3 and amplification of 1p22.2,7p22.2,7q22.2,7q21.11,8q24.23,9q33.3-34.2,17q24.3-25.2.Some of the changes were in accordance with two groups,such as deletions of 4q,5q,13q, 8p22-23.2,21q21.1-21.3 and gains of 3q,17q,19p,8q24.23.But the frequency of aberration occurred in the two groups were different oberviously.Some mutations were most happened in high risk group.They are losses of 3p,4p,9p,18q,1p12-34.2, 12q21.31-21.33 and gains of 16p,16q,22q,1p22.2,7p22.2,7q22.2,7q21.11, 9q33.3-34.2,17q24.3-25.2.Gain of 19q was the only mutation that happened frequently in low risk group.Moreover,ten candidate marker genes(SLC30A7,PTBP2,CCDC99, KIF13A,Cllorf59,SLC12A4,LOC348180,CDH15,ZCCHC2,AF315098) for distinguishing the two groups were identified.Conclusion:The DNA copy number alterations closely associate with lymph node metastasis in LSCC and may play an important role in prediction of metastasis and patient survival.