SP140 Is Selected As A Potential Prognostic Biomarker For Kidney Renal Clear Cell Carcinoma (KIRC) Based On Bioinformatic Analysis

Objective:This study aimed to explore the relationship between speckled protein 140(SP140)and prognosis in kidney renal clear cell carcinoma(KIRC)and explore the underlying mechanism,which will provide basis for SP140 as a prognosis biomarker in KIRC patients.Methods:(1)The difference expression of SP140 in various types of cancers was analyzed through TIMER and UALCAN database.(2)GEPIA and UALCAN databases were used to evaluate the relationship between SP140 and prognosis in cancer patients.(3)TIMER database was used to analyze the correlations between SP140 and prognosis biomarkers of KIRC,and UALCAN database was utilized to further analyze the expression and prognosis effects of reported prognosis biomarkers in KIRC.(4)GSEA was utilized to identify the main function of SP140 in KIRC.(5)TIMER database was performed to analyze the relationships between SP140 and tumor immune infiltration and immune marker genes.(6)Experimental verification.Results:(1)The differential expression analysis showed that SP140 was higher expression in breast invasive carcinoma(BRCA),head and neck squamous cell carcinoma(HNSC),KIRC,kidney renal papillary cell carcinoma(KIRP),and uterine corpus endometrial carcinoma(UCEC)compared to the normal tissues,but significantly lower expression in colon adenocarcinoma(COAD),kidney chromophobe(KICH),lung squamous cell carcinoma(LUSC)and rectum adenocarcinoma(READ).(2)Survival analysis showed that high SP140 expression was associated with poor prognosis in KIRC patients.(3)The correlation analysis showed that SP140 expression was positively correlated with adverse prognostic biomarkers like CXCL13,CEP55,CD44,EZH2,RRM2,CDC20 and FOXM1,while negatively correlated with the favorable prognostic biomarker TSPAN7.Besides,CXCL13,CEP55,CD44,EZH2,RRM2,CDC20,and FOXM1 were highly expressed and positively correlated with poor prognosis in KIRC,while TSPAN7 was lowly expressed and positively correlated with better prognosis in KIRC.(4)Gene set enrichment analysis showed that SP140 was mainly involved in immune signaling pathways such as activation of“leukocyte”,“lymphocyte”,“adaptive immune response”,“myeloid leukocyte”and“natural killer cell”;proliferation of“leukocyte”and“T cell”;production of“interleukin 1”;differentiation of“lymphocyte”and so on in KIRC.(5)Immune infiltration analysis showed that SP140 expression was positively associated with infiltration levels of B cells,CD4~+T cells,CD8~+T cells,neutrophils,macrophages,dendritic cells(DCs),and most immune cells’markers in KIRC.(6)Western blotting analysis showed that compared with human normal renal cells 293T,SP140 was highly expressed in human KIRC cells ACHN and Caki-1,which was consistent with the results of bioinformatics analysis.Conclusions:In KIRC,SP140 might influence the prognosis of KIRC patients by regulating tumor immune infiltration,and SP140 may be a poor prognosis biomarker in KIRC patients.