Genomic Research Of Preoperative Neoadjuvant Chemoradiotherapy Resistance In Rectal Cancer And Esophageal Carcinoma

Part1 Genomic Research of Neoadjuvant Chemoradiotherapy Resistance in Rectal CancerObjective Based on weighted gene co expression network analysis(WGCNA),we searched for markers to predict the efficacy of radiotherapy and chemotherapy for rectal cancer at the molecular level.Methods The genome-wide expression data(GSE119409)of patients receiving radiotherapy and chemotherapy were obtained from the Gene Expression Omnibus(GEO).The network modules of pathological complete response(p CR)group and non pathological complete response(non PCR)group were constructed by WGCNA method,and the network modules were tested KEGG analysis.Netrep method was used to evaluate the conservatism of the network module and determine the characteristic module.The pivot genes of the constructed network module were screened by analyzing the gene related attributes in the network,the hub genes of the constructed network module are screened.RT-PCR was used to verify the relationship between the selected genes and chemoradiotherapy resistance of rectal cancer.Results In this study,11 network modules of p CR group and 10 network modules of np CR group were constructed by WGCNA method.Five modules including black,blue,green,yellow and purple were obtained from the conservative evaluation of network module,which were considered to be related to chemoradiotherapy resistance.Five core hub genes including SLC22A14、SIDT2、CABP4、EPHB6 and RAB11 B were further obtained.RT-PCR was used to verify the above five hub genes: Compared with n PCR group,the expression of EPHB6 and RAB11 B was higher in PCR and lower in SIDT2(t=2.661,P=0.0238;t=2.334,P=0.0418;t=2.478,P=0.0326).The difference was statistically significant;Sl C22A14 and CABP4 were highly expressed in PCR group(t=1.674,P=0.1252;t=1.818,P=0.0992),and the difference was not statistically significant.Conclusions The enrichment of five key modules GO and KEGG showed that the modules were involved in biological processes such as non homologous recombination repair and organic matter transport;It is significantly enriched in Ras signaling pathway,PI3K-Akt signaling pathway and other pathways.PCR verification found that the expression of EPHB6,SIDT2 and RAB11 B in p CR group and np CR group was statistically significant,which was closely related to the radiotherapy resistance of rectal cancer and may be a predictor.Part2 Chemoradiotherapy Sensitivity of Esophageal Squamous Cell Carcinoma Based on Weighted Gene Co-expression Network AnalysisObjective Based on the method of weighted gene co expression network analysis(WGCNA),the pivotal genes affecting the prediction of chemoradiotherapy sensitivity of esophageal squamous cell carcinoma(ESCC)were found at the molecular level.Methods The whole genome expression data(GSE45670)of ESCC patients receiving radiotherapy and chemotherapy were obtained from the Gene Expression Omnibus(GEO).The WGCNA method was used to construct the network module of pathological complete response(p CR)group and non pathological complete response(non PCR)group.GO and KEGG analysis of the constructed modules.Using the combination of zsummary and medianrank measurement methods to evaluate the conservatism of each module and determine the characteristic network module.By analyzing the gene related attributes in the network,the hub genes of the constructed network module are screened.Results Eight modules were detected in PCR group and five modules were detected in n PCR group.Five characteristic modules of yellow,blue,black,green and red were obtained by conservative evaluation method.Five hub genes related to chemoradiotherapy sensitivity of esophageal squamous cell carcinoma,such as MICAL2,EPHB6,COMMD8,EPS15L1 and RBPMS,were screened.Conclusion The enrichment of five key modules go and KEGG showed that: clearing apoptotic cells,positive regulation of cell growth and other biological processes;It is significantly enriched in multiple signal pathways such as oxidative phosphorylation and p53 signal pathway.Through comprehensive analysis of the attributes of network members,five molecules such as MICAL2,EPHB6,COMMD8,EPS15L1 and RBPMS may be used to predict the effect of preoperative radiotherapy and chemotherapy of ESCC.