Study On The Predictive Value Of Absent In Melanoma 2 In Predicting The Prognostic And Immunotherapy Response Of Clear Cell Renal Cell Carcinoma

Background:With the development and diversification of cancer treatment,especially the rise of immunotherapy,great breakthrough has been made in the treatment of clear cell renal cell carcinoma(ccRCC).In order to guide the cancer treatment and improve the therapeutic response,biomarkers are widely used to predict the prognosis of cancer patients and the therapeutic value of cancer-related therapies.However,there is still a lack of an economical and effective biomarker to predict the effect of immunotherapy in ccRCC patients.As an indispensable component of the inflammasome,absent in melanoma 2(AIM2)plays an essential role in the initiation of the innate immune response,while its effects on clear cell renal cell carcinoma(ccRCC)still remain unclear.In this research,we aimed to evaluate the predictive value of AIM2 on prognosis and immunotherapy effects in patients suffering from ccRCC.Methods:In this study,raw data obtained from The Cancer Genome Atlas(TCGA)database,Gene Expression Omnibus(GEO)database and International Cancer Genome Consortium(ICGC)database,and ccRCC patient samples from Department of Urology,NanFang hospital were collected for exploring the correlation between AIM2 and ccRCC progression.The methylation and copy number variation(CNV)levels of AIM2 were investigated to explore the reasons for the differential expression of AIM2 in ccRCC patients.Meanwhile,Cox regression analyses were performed to confirm the prognostic value of AIM2 on the survival outcomes of ccRCC patients.In addition,gene-set enrichment analysis(GSEA),single sample gene set enrichment analysis(ssGSEA),ESTIMATE algorithm,CIBERSORT algorithm,single-cell sequencing analysis and other bioinformatics methods were used to investigate the correlation between AIM2 and tumor immune microenvironment(TIME)in ccRCC patients.Finally,the accuracy of AIM2 in predicting the efficacy of immunotherapy response in ccRCC patients was demonstrated by several methods,including T-cell inflammation signature(TIS)scores,immunologically tumor typing,and Submap algorithm.The above results were then verified in multiple cohorts.Results:In our study,we demonstrate that AIM2 expression is significantly higher in clear cell renal cell carcinomas in comparison to adjacent normal tissues with the potential contributing factors including low methylation level and high copy number amplification level of AIM2.Moreover,a high expression level of AIM2 is considered to be an effective predictor of poor prognosis in ccRCC patients,showing a remarkably positive correlation with tumor progression,invasion and metastasis.Further analysis suggested that AIM2 was implicated in tumor immune microenvironment with a majority of immune cells infiltrating and immune-related pathways up-regulating in AIM2 high-expression subgroup.However,overexpression of AIM2 is also found to be closely correlated with the high expression level of most immune checkpoints.Thus,we further discovered that the ccRCC patients with higher expression level of AIM2 was inclined to more probably respond to immunotherapy,confirming that AIM2 could accurately predict the therapeutic response of immune checkpoint inhibitors(ICIs)in ccRCC patients.Conclusion:This research determined the predictive value of AIM2 in predicting the prognostic and immunotherapy effects of ccRCC patients,which revealed that AIM2 expression levels can be utilized to efficiently pick out certain patients that may benefit from cancer immunotherapy.