Abstract: Objective To investigate the correlation of stress-inducible phosphoprotein 1 (STIP1) expression level with prognosis of different cancers and its potential role in immunotherapy. Methods TCGA, TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers. We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues. We further analyzed the correlation of STIP1 expression level with tumor mutational burden, microsatellite instability, immune cell infiltration, immune regulators and outcomes of different cancers. STIP1- related proteins were identified using protein- protein interaction (PPI) network analysis, and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1. Results Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues (P<0.05), which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues. STIP1 expression level was correlated with clinical stages of multiple cancers (P<0.05), and in some cancer types, an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival, disease-specific survival, disease-free survival and progression-free survival (P<0.05). STIP1 expression was significantly correlated with tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors in most tumors (P<0.05). PPI network analysis indicated that STIP1-related proteins included HSPA4, HSPA8, and HSP90AA1. KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism, tryptophan metabolism, and butyrate metabolism pathways; HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism. Conclusion STIP1 is up- regulated in multiple cancer types and its expression level is correlated with clinical tumor stage, tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors.

Key words: stress-inducible phosphoprotein 1; stress induced phosphoprotein 1; immune-related gene; pan-cancer analysis