Prognostic And Immunological Role Of PDLIM2

Purpose:The protein PDLIM2 regulates the stability of various transcription factors and is required for polarized cell migration.The expression of PDLIM2 is dysregulated in a variety of cancers.Studies have proved that it plays an important role in the occurrence and development of some cancers.However,the prognosis,metastasis and immune infiltration of PDLIM2 in pan-cancer are not well-understood.At the same time,the PDZ domain of PDLIM2 is considered to be a valuable drug target for tumor diseases,and PDLIM2 is considered to be a target for epigenetic drugs in lung cancer.This paper aims to use bioinformatics analysis methods to clarify the role of PDLIM2 in tumor development,explore the regulatory mechanism of PDLIM2 in immune infiltration,observe the ability of PDLIM2 to predict the efficacy of tumor immunotherapy,explore the potential association between PDLIM2 and immunotherapy,and detect the feasibility of PDLIM2 as a drug target for combination therapy.This paper aims to provide reference for realizing personalized anti-tumor immunotherapy strategies.Methods:Gene expression profiles,mutation data,and clinical information of 33 kinds of tumors in TCGA was downloaded from UCSC Xena.The Wilcoxon test was used to analyze the differential expression of PDLIM2 between normal tissues and tumor tissues in 33 kinds of cancers,and GEPIA2 database was utilized to supplement the analysis.The "survival"package was used for survival analysis to find the cancer types related to survival of PDLIM2 expression.The "limma" package was used to analyze the differential expression of PDLIM2 in different clinical stages.The TIMER database was utilized to detect associations of PDLIM2 with levels of immune infiltration of six immune cells in urothelial carcinoma of the urinary bladder,colon carcinoma,and renal papillary cell carcinoma.The"limma" package was used to estimate the co-expression of PDLIM2 with immunologic markers.The "ESTIMATE" package was used to calculate the immune and matrix scores in renal papillary cell carcinoma and bladder carcinoma.The correlation between PDLIM2 and two immune scores was calculated.Then,the value of tumor mutational burden was calculated from the mutation data of 33 kinds of tumors in TCGA database.The correlation between PDLIM2 and tumor mutational burden,microsatellite instability,immune score and stromal score was analyzed.At last,the co-expression relationship between PDLIM2 and immune checkpoint was assessed.Results:Compared with cancer tissues,PDLIM2 was highly expressed in normal paraneoplastic tissue of various cancers.PDLIM2 significantly affected the prognosis of various cancers based on the analysis of three survival indicators.PDLIM2 was significantly correlated with the clinical stage in seven types of tumors.The expression level of PDLIM2 was positively correlated with macrophages and dendritic cells in bladder cancer;CD4+T cells,macrophages,neutrophils and dendritic cells in colon cancer;and B cells,CD8+T cells,and dendritic cells in papillary renal cell carcinoma,and negatively correlated with tumor purity in three tumors.The co-expression analysis revealed that the expression levels of most immunerelated genes in monocytes,tumor-associated macrophages,M2 macrophages,dendritic cells,and T cell exhaustion were positively correlated with the expression of PDLIM2.In the analysis with immunotherapeutic indicators,PDLIM2 expression was associated with the tumor mutation burden in 12 cancer types and microsatellite instability in 5 cancer types.Furthermore,PDLIM2 expression levels were positively correlated with stromal scores in 21 tumors and with immune scores in 17 tumors.The co-expression analysis showed that the level of PDLIM2 was closely related to the expression of various immune checkpoints in many cancers.Conclusion:PDLIM2 may be associated with the development,progression and invasion of various cancers.PDLIM2 significantly affects the prognosis of various cancers.Its dysregulated expression has both pro-and anti-cancer effects,and has different prognosis depending on the cancer type.PDLIM2 is involved in immune regulation in the tumor microenvironment,and it may interact with immune checkpoints to affect the efficacy of immunotherapy,proving the feasibility of PDLIM2 as an epigenetic drug target for combination therapy.