| Background Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death and one of the most common malignant tumors in the world. The five-year survival rate is less than fifteen percent, and the mortality rate can be obviously decreased by early detection. Lung adenocarcinoma is concerned as a major subtype of non-small cell lung cancer which confirmed by the research of pathology and molecular mechanism. However, the key of early detection is to identify the abnormity of genetic and molecular in lung adenocarcinome. Recently, several researchers demonstrated that more than ninety percent of DNA is transcribed, but only 2% of the transcripts are protein-coding genes, and the most of the transcripts are non-coding RNAs. New evidences suggest that non-coding RNA might play vital role in many biological processes. The non-coding RNAs include small RNA,long non-coding RNA(lncRNA), and circRNA etc. In recent years, emerging evidences indicated that lncRNAs were dysregulated in tumourigenesis and tumor progression of many cancers, such as lung cancer, liver cancer and prostate cancer. In the present study, our goal is to screen the key lncRNAs which play important roles in the occurrence and development of lung adenocarcinoma. We used two meta-analysis methods to analysis 9 microarray data sets which were downloaded from GEO database, validated the lncRNA expression by quantitative real time PCR, and provided a new idea and scientific basis for molecular diagnosis and treatment of lung adenocarcinoma.Methods 1. Use two meta-analysis methods to analysis the microarray data sets and screen several long non-coding RNAs which may influence the occurrence and development of lung adenocarcinoma.2. Use quantitative real time PCR to validate the expression abundance of LINC00968 in ten lung adenocarcinoma samples and paired adjacnet lung tissues.Results Use effect size and rank products methods to analysis 9 microarray data sets which were produced from Affymetrix U133 Plus 2.0 platform and to screen twenty-seven lncRNAs which may related with the occurrence and development of lung adenocarcinoma. Among these lncRNAs, eight are up-regulated and twenty-one are down-regulated. They are LINC00551, LOC100507632, FOXF1-AS1, LOC145837, LOC338758, LOC100505989, ENSG00000259071, ENSG00000241732, BRE-AS1, LOC100288911, TBX5-AS1, LOC401093, KDM5B-AS1, RNF157-AS1, ENSG00000261658, PGM5-AS1, LOC285812, LOC100505495, ENSG00000261685, ENSG00000261179, LOC100499467, ENSG00000224220, LOC731424, ENSG00000250280, LOC731424, ENSG00000250280, LOC731424, LOC285043, and LOC644242. A meta-analysis of 9 independent NSCLC datasets identified four genes (RP11-38P22, ENSG00000248771, ENSG00000245750) which are significantly and consistently over-expressed in ADC across all datasets, and are able to distinguish ADC samples from normal lung samples or SCC. The expression of LINC00968 in lung adenocarcinoma is significantly down-regulated (P value 8.47E-17).Conclusions 1. According to the NetAffx annotation of probe sets and the Ref-seq and Ensembl annotations of lncRNAs, we identified 2935 probe sets corresponding to lncRNA genes on the Affymetrix HG-U133 Plus 2.0 arrays.2. A meta-analysis of 9 independent NSCLC datasets identified three genes (RP11-38P22, ENSG00000248771, ENSG00000245750) which were significantly and consistently over-expressed in ADC across all datasets, and were able to distinguish ADC samples from normal lung samples or SCC. The results indicate these lncRNAs may play an important role in lung adenocarcinoma occurrence and development.3.The obvious down-regulation of LINC00968 in lung adenocarcinoma tissues suggests that it may be an anticancer non-coding RNA.4. The low expression of LINC00968 may increase mutation, promote cell proliferation and accelerate the carcinogenic process, which has a potentially important value for the treatment and prognosis of lung adenocarcinoma. |
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