Abstract:

Objective To discuss the expression level of macrophage scavenger receptor 1 （MSR1） in pan-cancer tissue，survival and immune characteristics of the patients by bioinformatics analysis， and to elucidate the value of MSR1 as a new biomarker for the tumor diagnosis， prognosis， and immunotherapy. Methods Clinical Bioinformatic Database and Sangerbox Database were used to analyze the expression levels of MSR1 mRNA in normal tissue and tumor tissue，the expression of MSR1 protein was analyzed by The Human Protein Atlas（HPA） Database，and univariate survival analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of MSR1，and the expressions of MSR1 in various types of cells were analyzed with single-cell sequencing results from Tumor Immune Single-cell Hub （TISCH） Database；Tumor Immune Estimation Resource （TIMER2.0），Tumor Immune Syngeneic Mouse （TISMO）， Tumor Immune Dysfunction and Exclusion （TIDE）， and Gene Set Cancer Analysis （GSCA） Databases were used to analyze the correlations between the MSR1 expression level in pan-cancer tissue and immune cell infiltration， immune checkpoint gene expression， and immune treatment response. Results Compared with normal tissue， the expression levels of MSR1 mRNA in 17 kinds of tumor tissues including breast invasive carcinoma （BRCA），colon adenocarcinoma （COAD），esophageal carcinoma （ESCA）， glioblastoma multiforme （GBM）， head and neck squamous cell carcinoma （HNSC），kidney renal clear cell carcinoma （KIRC）， kidney renal papillary cell carcinoma （KIRP），brain low-grade glioma （LGG），liver hepatocellular carcinoma （LIHC），ovarian serous cystadenocarcinoma （OV），pancreatic adenocarcinoma（PAAD），prostate adenocarcinoma （PRAD），skin cutaneous melanoma （SKCM），stomach adenocarcinoma （STAD），testicular germ cell tumor （TGCT），thyroid carcinoma （THCA）， and uterine carcinosarcoma （UCS） were increased（P<0.01）；compared with normal tissue，the expression levels of MSR1 protein in breast cancer， endometrial cancer， liver cancer， ovarian cancer， skin melanoma， testis cancer， pancreatic cancer， and prostate cancer tissues were increased in varying degrees. The high expressions of MSR1 in bladder urothelial carcinoma ［BLCA， hazard ratio（HR）=1.01， P=0.047， 95%CI（1.00，1.03）］， LGG ［HR=1.03， P<0.001， 95%CI（1.02，1.04）］， LIHC ［HR=1.04， P=0.007， 95%CI（1.01，1.07）］， OV ［HR=1.02，P=0.028， 95%CI（1.00，1.03）］， STAD ［HR=1.02， P=0.016， 95%CI（1.00，1.04）］， THCA［HR=1.06，P=0.006， 95%CI（1.02，1.11）］ and uveal melanoma ［UVM， HR=1.18，P=0.044， 95%CI（1.00，1.40）］ were correlated with the poor overall survival（OS） of the patients； the high expression of MSR1 in LGG ［HR=1.03，P<0.001， 95%CI（1.02，1.04）］，the uterine corpus endometrial carcinoma （UCEC］， ［HR=1.05， P=0.038， 95%CI（1.00，1.10）］， and UVM ［HR=1.2，P=0.036， 95%CI（1.01，1.41）］ was correlated with poor disease-specific surival（DSS）.The single-cell sequencing results indicated that MSR1 was mainly expressed in the dendritic cell（DC） and monocyte-macrophage. The MSR1 expression was positive correlated with various kinds of immune cell infiltrations（P<0.05），including CD8+ T lymphocytes， natural killing（NK） cells， regulatory T lymphocytes， and cancer associated fibroblasts（CAF）. There were significant positive correlations between MSR1 and classical immune checkpoint gene and immunotherapy response marker （P<0.05）. Conclusion MSR1 is highly expressed in lots of tumor tissues and is closely associated with the poor prognosis and immune factors of lots of tumor patients. MSR1 may be a diagnostic tumor marker and a predictor of tumor prognosis and immunotherapy efficacy， and has the potential to be a new therapeutic target.

Key words: Macrophage scavenger receptor 1, Pan-cancer, Immunotherapy, Tumor microenvironment, Lipid metabolism