Expression Pattern Of WNT Signaling In Different Cancers And Mining Of Tumor Biomarks Characterized By Multiple Genes Co-expression Pattern

The mining of tumor specific biomarkers is important for the research of tumor development mechanism and tumor prevention or treatment.Tumor biomarkers include nucleic acid,protein,metabolite,etc.As tumor types are diverse,and there are various differences in tissue specificity and tumor heterogeneity.Digging the molecular characteristics of different types of tumor should be of benefit to provide theoretical support for the research and prevention of tumor regulation mechanism.Our previous work found that WNT signaling pathway is related to the development of many kinds of malignant tumors.In this study,we attempts to explore whether the WNT signaling pathway has tumor specific expression patterns.Based on this,we will discuss whether it can be used as a biomarker to characterize specific tumors.Firstly,we combined TCGA(the Cancer Genome Atlas)tumor sequencing data with GTEX(genotype tissue expression)human normal tissue sequencing data,and found that ligands and receptors or co-receptors of WNT signaling pathway have specific expression patterns in different types of tumors.Compared with normal tissues,the expression of WNT3 and WNT4 m RNA in melanoma decreased;WNT3 m RNA increased significantly in chronic lymphoblastic leukemia;WNT5A m RNA and WNT7 B m RNA were upregulated in a variety of epithelial squamous cell carcinomas(ESCC).Compared with normal tissues,SDC3 m RNA was up-regulated in melanoma and glioma;LRP5 m RNA was up-regulated in various adenomas;However,GPC1 m RNA,FZD6 m RNA,FZD7 m RNA and PTK7 m RNA were up-regulated in a variety of ESCC.Then,we used immunohistochemical method to detect the expression of WNT5 A,WNT7B,GPC1 and FZD7 in lung squamous cell carcinomas tissue chips.The results showed that the expression of WNT5 A,WNT7B,GPC1 and FZD7 in lung squamous cell carcinoma was significantly higher than that in adjacent normal tissues.In addition,considering that the secretory proteins of this pathway may exist in the exosomes,we used lung squamous cell carcinoma celllines to investigate the relationship between exosomes and WNT signal proteins.WNT7 B,GPC1,SDC1 and FZD7 were expressed in NCI-H226 and SK-MES-1 cell lines.Furthermore,GPC1 was highly abundant in the exosomes of the two cell lines,suggesting that GPC1 may be a potential circulating tumor marker candidate for lung squamous cell carcinoma.Since both the sequencing data and clinical sample verification showed that WNT7 B and WNT5 A were up-regulated in ESCC,we then tried to explore the possible coexpression regulation mechanism from the perspective of transcriptional regulation by means of bioinformatics analysis.With ALGGEN(http://alggen.lsi.upc.es/)And Cistrome Data Browser(http://cistrome.org/db/),we predicted some co-regulation transcription factors of WNT7 B and WNT5 A.Then,the expression of these predicted transcription factors in tumor samples of patients with lung squamous cell carcinoma in TCGA database was analyzed.We found that MYC,RAD21,H2AZ2,H2AZ1,NFE2L2 were all highly expressed in lung squamous cell carcinoma;while POLR2 A,NFE2L2and YAP1 were positively correlated with the expression of WNT5 A and WNT7 B.In addition,in order to develop more accurate multi-parameter tumor markers,based on TCGA sequencing data,we introduced t-distributed stochastic neighbor embedding(tSNE)dimensionality reduction and visualization analysis method to preliminary explore multi-dimensional and specific tumor marker spectrum.