The Expression And Significance Study Of LncRNA In Esophageal Squamous Cell Carcinoma

Backgroud Esophageal cancer is a highly lethal gastrointestinal malignancy,and the incidence of EC rank the eighth among all tumors.Despite treated aggressively, the overall five-year survival rate remains poor which is only10-20% after operation.The evidence indicated that the oncogenesis and development of esophageal cancer is the result of multifactors and multigenes,but the concrete oncogenic mechanism is not illuminated.Therefore, exploring the biological behavior and pathogenesis of EC is necessary for the development of better diagnostic methods, therapeutic strategies and survival.Long noncoding RNA is more than 200 nucleotides in length,without protein coding capacity and highly conserved in evolution,which abnormally regulate the gene expression through many ways.Lnc RNAs play important roles in diverse biological process including development,cell differentiation,proliferation,apoptosis,hormone secretion and oncogenesis.Recently,cumulative evidences have shown that the generation and dysfunction of lncRNAs are associated with the occurrence and development of tumors and function as oncogenes or tumor suppressor genes.Objective Review of the literature reveales that the study about the pathological process of esophageal carcinoma in tumorigenesis and progression is still blank.Therefore,this study would screen the lncRNA expression spectrum of esophageal cancer through the microarray, then further study of lncRNA expression spectrum and aberrant expression of lncRNAs in EC would be helpful to reveal the mechanism of EC and provide new ideas for early diagnosis, prognosis and therapeutic strategies.Methods We first use Human Lnc RNA Array v3.0 to screen the abnormal expression of lncRNA and corresponding RNA in five esophageal squamous cell carcinoma and matched normal tissues,then through real-time fluorescent quantitative polymerase chain reaction technology verifying and determining the special lncRNA.Subsequently,according to the microarray results and literature reports, we selected 12 out of 45 candidate lncRNAs to perform real-time quantitative PCR(q RT-PCR) in same five pairs of samples and found that four lncRNA(HOXA11-AS?LINC00467?GAS5?SACS-AS1) are abnormally expressed. Then, we verificated the four lncRNAs and confirmed their specificity in ESCC from another 42 pairs of samples. Combination with the clinical data,we analyse the significance of the specific abnormal expression of lncRNAs in ESCC stage,prognosis and chemotherapy and so on.Results The microarray indicates that there are 1607 up-regulated lncRNAs and 2099 down-regulated lncRNAs(fold-change > 2.0and P-value<0.05)in five esophageal squamous cell carcinoma tissues comparing with the normal esophageal tissues.Then they use real-time fluorescent quantitative polymerase chain reaction technology to identify the lncRNAs in the five same samples,implying that there are four abnormally special expression lncRNAs.That is to say,the high expression of lncRNA LINC00467?HOXA11-AS and GAS5 and the low expression of lncRNA SACS-AS1 in esophageal caricinoma comparing with the noncancerous tissues are statistical difference.But our data indicates that the long noncoding RNA HOXA11-AS has higher positive rate in the cancer tissues than the noncancerous tissues,at the same time,the difference is statistically significant(P<0.05). But the long noncoding RNA SACS-AS1 has higher negative rate in the cancer tissues than the noncancerous tissues and the difference is statistically significant(P<0.05).They are consistent with each other.The relative expression of the two lncRNAs in cancer tissues and noncancerous tisses are connected with the stage of tumor,lymph node metastasis,the degree of tumor differentiation,the location of tumor(P<0.05),but it has nothing to do with the age and sex(P>0.05).Conclusions We uncovered the profiles of differentially expressed lncRNAs between normal and esophageal carcinoma tissues by using the microarray techniques, and found that the lncRNA HOXA11-AS is up-regulation in esophageal carcinoma and the lncRNA SACS-AS1 is down-regulation in esophageal cancer. The relative expression of the two lncRNAs in cancer tissues and noncancerous tisses are connected with the stage of tumor,lymph node metastasis,the degree of tumor differentiation,the location of tumor.But it has nothing to do with the age and sex.This study affords expression profiles of lncRNAs between esophageal squamous cell carcinoma tissues and normal esophageal tissues, which could provide database for further research about the function and mechanism of key-lncRNAs in esophageal squamous cell carcinoma, and may be helpful to explore potential diagnosis factors and therapeutic targets for esophageal squamous cell carcinoma.