Explore Genomics In Locally Advanced CSCC And The Relationship With Chemosensitivity And Prognosis Based On Bioinformatics Analysis

Objective:Cervical cancer is one of the most common malignant tumors in women and major cause of cancer death in women.Although concurrent chemoradiotherapy has improved the treatment of cervical cancer,due to the heterogeneity of the tumor to chemotherapy or radiation therapy,even in patients with similar physical conditions and pathological characteristics,the patients respond differently to the same therapeutic regimen,furthermore some patients get rapid progression.In recent years,it has become a research hotspot to explain this phenomenon of individual differences from the perspective of molecular biology.Therefore,we attempted to analyze the potential relationship between genomic mutation and cisplatin sensitivity and survival in stage IIB-? Cervical Squamous Cell Carcinoma(CSCC)patients.Methods:Clinical information and sequencing data of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma(CESC)in Genomic Data Commons(GDC)data portal were obtained through TCGAbiolinks.Only patients with stage IIB-IV CSCC who received concurrent chemoradiotherapy based on cisplatin were included.Then the gene mutation data of these patients were analyzed.First,univariate Cox regression analysis was used to find out the factors affecting PFS and OS.Next,multivariate Cox regression analysis was used to analyze the factors that had independent influence on survival and prognosis under the condition of controlling variables.Cisplatin sensitivity data and sequencing data of CESC cell lines were obtained from the Genomics of Drug Sensitivity in Cancer(GDSC)to analyze the relationship between gene mutation and cisplatin Sensitivity.Finally,Kaplan-Meier survival analysis,differentially expressed gene analysis,GO annotation analysis and KEGG fiunctional enrichment analysis were used to further explore the role of mutation in survival prediction and cisplatin treatment sensitivity.Results:A total of 52 patients with stage IIB-? CSCC were enrolled.77 genes with mutation frequency>10%were included in final analysis.Multivariate Cox regression analysis showed that the mutation of Rbl was an independent predictor of overall survival(OS)(HR=0.06,95%CI 0.01-0.59;P=0.02).Patients with mutant Rbl had better overall survival(134.2 versus 86.8 months)compared with patients with wild-type Rbl,The half maximal inhibitory concentration(IC50)of the mutant Rbl cell line to cisplatin was significantly lower than that of the wild-type cell line(3.49 versus 10.15?M,P = 0.038).A total of 332 differently expressed genes(DEGs)were identified and the KEGG pathway enrichment analysis showed that most DEGs were enriched in the PI3K/AKT pathway(P = 0.015).Conclusions:We found that Rbl mutation was an independent survival predictor in stage IIB-IV CSCC,and patients with Rbl mutation may be more sensitive to cisplatin.The varied sensitivity of CSCC to cisplatin may be caused by regulating PI3K/AKT pathway.