Prognostic significance of SPARC expression in pan-cancer and its relationship with immune microenvironment
Objective To investigate the gene expression level of secreted protein acidic and rich in cysteine(SPARC)in various human tumor tissues and its prognostic significance as well as its relationship with immune microenvironment.Methods The transcriptome profiles,somatic mutation data and clinical prognostic data were obtained by using multiple data sources,including The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx)and Cancer Cell Line Encyclopedia(CCLE)databases.The ESTIMATE and TIMER algorithms were applied to evaluate the immune microenvironment in pan-cancer.On this basis,the gene expression level of SPARC in pan-cancer and its relationship with tumor prognosis,immune infiltration,immune checkpoint genes,tumor mutation burden and microsatellite instability were analyzed.Functional enrichment analysis was performed on SPARC-related genes.Finally,real-time PCR was used to validate the expression of SPARC in tumors in vitro.The effects of SPARC on the proliferation of different tumor cells were investigated by cell counting kit-8(CCK-8)assay.Results Compared with normal tissues,SPARC was highly expressed in 18 kinds of tumor tissues,including esophageal carcinoma,liver hepatocellular carcinoma,stomach adenocarcinoma,colon adenocarcinoma,acute myeloid leukemia,pancreatic adenocarcinoma,kidney renal clear cell carcinoma,adrenocortical carcinoma,ovarian serous cystadenocarcinoma,skin cutaneous melanoma,brain lower grade glioma,rectum adenocarcinoma,breast invasive carcinoma,cholangiocarcinoma,glioblastoma multiforme,head and neck squamous cell carcinoma,thyroid carcinoma and uterine carcinosarcoma(all P＜0.05).In 5 kinds of tumor tissues,such as cervical squamous cell carcinoma and endocervical adenocarcinoma,kidney chromophobe,prostate adenocarcinoma,lung adenocarcinoma and uterine corpus endometrial carcinoma,the gene expression of SPARC was relatively lower(all P＜0.05).Overall survival analysis showed,in 6 types of tumor including adrenocortical carcinoma(HR=1.40,P=0.030 0),bladder urothelial carcinoma(HR=1.19,P=0.000 5),kidney renal papillary cell carcinoma(HR=1.37,P=0.007 9),stomach adenocarcinoma(HR=1.21,P=0.002 9),uveal melanoma(HR=2.07,P=0.000 7)and mesothelioma(HR=1.33,P=0.000 6),patients with a high expression of SPARC had a poor prognosis.Whereas,low SPARC expression led to worse prognosis in kidney renal clear cell carcinoma(HR=0.83,P=0.006 5).The expression level of SPARC was positively correlated with the infiltration abundance of many types of immune cells in pan-cancer(P＜0.05),especially macrophages.Moreover,SPARC had a significant correlation with the majority of immune checkpoint genes including PDCD1 and CTLA4,as well as the biomarkers of immunotherapy response like TMB and MSI(P＜0.05).The proliferation of tumor cells was suppressed when the expression of SPARC was knocked down in HepG2,SNU-449 and HGC-27 cell lines.Conclusions The gene of SPARC was expressed abnormally in different types of tumors,whose expression levels affected clinical prognosis and had a close relation with immune characteristics of tumor patients.It was suggested that SPARC could be a biomarker for tumor prognosis and immunotherapy response evaluation,and had a potential to be a new target for oncotherapy.
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