Transcriptome-based Integrated Analysis And Research Of Pan-gynecological Tumor Immune Infiltration

Gynecological tumors,such as breast cancer,ovarian cancer and cervical cancer,have been seriously endanger the health of women all over the world,and how to effectively treat them has always been a worldwide problem.Immunotherapy can be combined with chemotherapy,targeted therapy and radiotherapy.How to rationally apply immunotherapy in combination therapy is one of the important development directions for cancer treatment in the future.The purpose of tumor immunity is to stimulate or mobilize the body’s immune system,enhance the anti-tumor immunity of the tumor microenvironment,and thereby control and kill tumor cells.Chemokines,autophagy genes,and tumor mutation burden(Tumor Mution Burden,TMB)can directly or indirectly affect the immune process,but their specific effects on immune infiltration in the occurrence and development of cancer are still unclear.The effects of chemokines and mutations in autophagy gene on tumor immune invasion and prognosis also need further evaluation.Herein,the common gynecological tumors as the research objects,this study integratively analyzes the relationships between immune infiltration and chemokines,autophagy genes,TMB,respectively,and discusses the potential values in prognostic research from the three perspectives.We aim to provide data references for subsequent immunotherapy and potential drug targets.In this study,breast cancer,cervical cancer,endometrial cancer,uterine sarcoma and ovarian cancer were selected as the research objects.Based on the transcriptome and mutation data,the Estimate algorithm was used to calculate the immune scores of the samples and perform immune groupings.Differentially expressed genes were screened,and genes related to prognosis were then screened using multi-factor regression based on clinical data.The key prognostic genes were determined using survival analysis and then constructed a risk scoring model.Based on these crucial genes and the risk scoring model,we developed a prognostic analysis system that was easy to query and analyze using java.Finally,the associations of crucial genes and immune infiltration were estimated using Spearman correlation coefficients.The results showed that among chemokines and autophagy genes,CCR7,CXCL11,IFNG and TP53 had common or specific effects on immune infiltration and prognosis in multiple cancer types:(1)The analysis of the correlation between Chemotaxis and immune cells showed that CCR7 and others were positively correlated with high infiltration of T Cells and CD8 cells in many cancer types.High expression of CCR7 and high infiltration of T cells and CD8 were found in cervical cancer,endometrial cancer,and ovarian cancer.There was a significant positive correlation between cancer and breast cancer.At the same time,the high expression of CCR7 in cervical cancer,ovarian cancer and breast cancer was significantly positively correlated with the survival rate of patients,which was beneficial to the prognosis of patients.In addition,the risk prognosis software was constructed based on the multi-factor regression model.This software could easily visualize the clinical factors that affected the survival of the patient,and displayed the survival rate of the patient.(2)The correlation between autophagy genes and immune cells showed a significant positive correlation between IFNG and the degree of Macrophages M1 cell infiltration in cervical cancer,ovarian cancer and breast cancer,and the high expression level of IFNG was conducive to the prognosis of patients.The expression of CCR2 was significantly negatively correlated with the degree of activated dendritic cells in cervical cancer and endometrial cancer.(3)Furthermore,the results also showed that the mutations of chemokines and autophagy genes had a directly important impact on immune invasion and prognosis.For example,the mutation of CXCL9 in ovarian cancer might reduce the degree of Macrophages M1 invasion and lead to poor prognosis.IFNG mutations in endometrial cancer also reduced the degree of T cells regulatory infiltration.The results of the relationship between TMB content and survival of five gynecological tumors showed that in ovarian cancer and breast cancer,the higher the TMB content,the higher the survival rate of patients.T cell CD8,as a cytotoxic T cell,played an important role in recognizing specific antigens,and it was positively correlated with high TMB levels in ovarian cancer,cervical cancer,and endometrial cancer,which also implied that these patients might be more sensitive to immunotherapy drugs with better prognosis.In summary,to understand the role of immune infiltration-related factors in different cancer types and the impact on the prognosis,this study performs an integrative analysis of the relationship between immune infiltration and chemokines,autophagy genes,TMB from the three perspectives based on the transcriptome and mutation data of breast cancer,cervical cancer,endometrial cancer,uterine sarcoma and ovarian cancer,and simultaneously assesses the impact on the prognosis and developed related prognosis evaluation system.The results can provide theoretical guidance and data support for the immunotherapy of related gynecological tumors,and also provide new ideas for developing more effective clinical immunotherapy strategies.