Expressions of CLDN1 and insulin-like growth factor 2 are associated with poor prognosis in stage N2 non-small cell lung cancer  

作　　者：ZHANG Zhen-fa PEI Bao-xiang WANG An-lei ZHANG Lian-min SUN Bing-sheng JIANG Ri-cheng WANG Chang-li 

机构地区：[1]Department of Lung Cancer , Lung Cancer Center, Tianjin Medical University CancerInstitute & Hospital, National Clinical Research Center of Cancer, KeyLaboratory of Cancer Prevention and Therapy, Tianjin 300060, China

出　　处：《Chinese Medical Journal》2013年第19期3668-3674,共7页中华医学杂志（英文版）

基　　金：Thiswork was supported by grants from National Natural Science Foundation of China （No. 30801377, No. 81000899, No. 81201649） and Tianjin Municipal Science and Technology Commission Key Application Research Project （No. 11JCZDJC 18900）.

摘　　要：Background Patients with single station mediastinal lymph node （N2） non-small call lung ccancer （NSCLC） have a better prognosis than those with multilevel N2.The molecular factors which are involved in disease progression remain largely unknown.The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.Methods Gene expression analysis was performed using Agilent 4x44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients.Real-time reverse transcription （RT）-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed.Immunohistochemical staining for these validated genes was performed on formalin-fixed,paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.Results We identified a 14 gene expression signature by comparative analysis of gene expression.Expression of these genes strongly differed between single station and multilevel N2 NSCLC.Four genes （ADAM28,MUC4,CLDN1,and IGF2） correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients.Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.Conclusions Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC.Further,CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.Background Patients with single station mediastinal lymph node （N2） non-small call lung ccancer （NSCLC） have a better prognosis than those with multilevel N2.The molecular factors which are involved in disease progression remain largely unknown.The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.Methods Gene expression analysis was performed using Agilent 4x44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients.Real-time reverse transcription （RT）-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed.Immunohistochemical staining for these validated genes was performed on formalin-fixed,paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.Results We identified a 14 gene expression signature by comparative analysis of gene expression.Expression of these genes strongly differed between single station and multilevel N2 NSCLC.Four genes （ADAM28,MUC4,CLDN1,and IGF2） correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients.Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.Conclusions Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC.Further,CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.

关 键 词：stage N2 non-small cell lung cancer CLDN1 insulin-like growth factor 2 

分 类 号：Q57[生物学—生物化学] S852.43[农业科学—基础兽医学]