Downregulation Of KLK13 Promotes The Invasiveness And Metastasis Of Esophageal Squamous Cell Carcinoma

Background: Esophageal cancer occurs globally,leading eighth incidence rate and sixth mortality rate among all the cancers,and the overall five year survival rate remains below 20%.Esophageal cancer includes two general pathological types: esophageal squamous cell carcinoma(ESCC)accounts for about 70% of reported worldwide esophageal cancer cases,and esophageal adenocarcinoma(EAC)30% respectively.In the developing world,such as eastern Asia,ESCC has a elevated incidence rate;however,in North America and Europe,the incidences of ESCC are low.The lack of characteristic symptoms at the early onset stage and the lack of non-invasive screening tests lead to the high mortality among ESCC patients.However,if diagnosed earlier,the five year survival rate can be significantly improved to 80–90%.Thus,the identification of new potential molecular markers may help to elucidate,detect and treat this disease.Based on our previous studies,we analysed the m RNA levels of KLK13 in the tissues from 138 ESCC patients and the functions of KLK13 on the invasive and migratory potential of a series of ESCC cell lines.Methods and materials: KLK13 m RNA expression levels in both ESCC cancerous tissues and adjacent noncancerous tissues collected from 138 patients were measured using real-time reverse transcription-polymerase chain reaction(q RT-PCR).Then,the correlation between KLK13 and ESCC clinicopathologic features was analysed.In addition,use Kaplan-Meier method for overall survival curves,with the log-rank test for comparison,and Cox proportional hazards model for multivariate analysis.Furthermore,in vitro studies were performed to analyse the effects of KLK13 in ESCC cells.Results: KLK13 m RNA levels decreased notably in tumour tissues compared with those in adjacent noncancerous tissues.And decreased KLK13 m RNA levels indicated significant correlations with higher tumour grade,elevated TNM(UICC,2009)stage classification,deeper infiltration and more lymph node metastases.Decreased KLK13 m RNA levels also correlate with poor survival,which indicates that KLK13 m RNA expression may be a potential prognostic marker,although it could not be an independent prognostic factor by multivariate analysis.In vitro experiments of the ESCC cell lines KYSE150 and KYSE450 demonstrated that overexpression of KLK13 inhibits cell invasion and migration.Conclusion: KLK13 m RNA level may be a potential marker for diagnosis.KLK13 m RNA level could not be used as a prognostic factor.KLK13 could inhibit invasion and migration of ESCC cells and KLK13 activators may be therapeutic targets for ESCC.