Exploration Of An Autophagy-related Long Noncoding RNA Prognostic Signature And Analysis Of Immune Infiltration In Cervical Cancer

【Background】In this study,we aimed to investigate the signature of the autophagy-related lnc RNAs(ARLs)and perform integrated analysis with immune infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC).【Methods】The UCSC Xena and HADb databases provided the corresponding data.The ARLs were selected via constructing a coexpression network of autophagy-related genes(ARGs)and lnc RNAs.Univariate Cox regression analysis combined with LASSO regression and multivariate Cox regression analysis were utilized to screen lnc RNAs.The ARL risk signature was established by Cox regression and tested if it was an independent element bound up with patient prognosis.Time-dependent receiver operating characteristics curve analysis was used to evaluate the effectiveness of the model in predicting clinical patient outcomes,and the accuracy was assessed by using decision curve analysis,calibration curve and consistency index.Multivariate Cox regression was later used to analyze independent impact factors associated with prognosis and,meanwhile,whether treatment outcome and pathological classification were associated with risk scores.Gene enrichment analysis was used to identify potential pathways associated with the prognostic assessment model.We used the x Cell algorithm and ss GSEA to clarify the pertinence between immune infiltration and the expression of ARLs.Finally,we predicted the sensitivity of drug treatment as well as the immune response.The expression of target lnc RNAs was measured in cervical squamous cell carcinoma and adenocarcinoma cell lines by q RT-PCR.【Results】1.Three lnc RNAs related with autophagy(SMURF2P1,MIR 9-3 HG and AC005332.4)were selected and a prognostic risk assessment model based on autophagy was constructed.2.The risk score calculated using Cox regression analysis was an independent factor that could be assessed(HR=2.82,95%CI=1.874.30;p<0.001).3.Gene set enrichment analysis explored potential pathways related to the prognosis assessment model,and a total of six related pathways were obtained.4.The results of the immune-infiltration analysis showed that CD8~+naive T-cells(p=2.07 e-02),Endothelial cells(p=1.48 e-02),and Preadipocytes(p=3.14 e-03)were prominently enhanced in the group with higher risk scores.5.There were 10 therapeutic agents that varied significantly in their estimated half-maximal inhibitory concentrations in the two groups.6.According to the experimental validation,we found that SMURF2P1 belongs to the co-stimulatory genes and might assume greater importance in the development of cervical adenocarcinoma.MIR9-3HG and AC005332.4 belonged to the tumor-suppressor genes and they may play a more positive role in cervical squamous cell carcinoma.【Conclusions】The prognosis risk assessment signature based on three autophagy-related lnc RNAs(SMURF2P1,MIR9-3HG,and AC005332.4)could effectively predict patient outcomes.SMURF2P1 belonged to the onco-stimulating gene,and might have a greater role in the development of cervical adenocarcinoma.MIR9-3HG and AC005332.4 belonged to the tumor suppressor genes and they might play a more positive role in the development of cervical squamous cell carcinoma.And MIR9-3HG was highly expressed in tumors,but it was a protective gene.In terms of immune infiltration,CD8~+Tem might exert a positive immunological effect in the opposite side of CESC patients to inhibit distant tumor metastasis.Although the immune infiltration level of CD8~+Tem was negatively relevant to MIR9-3HG expression,it still showed the protective effect of CD8~+Tem.However,CD8~+Tcm may have a role in promoting tumor metastasis.