Exploring the Oncogenic Role of the Tumor “Suppressor” Oncostatin M (OSM)

Abstract

Background: Oncostatin M (OSM) has been reported to be a key regulating factor in the process of tumor development. Previous studies have demonstrated both promotion and inhibition effects of OSM in tumors, therefore inspiring controversies on it. However, no systematic assessment of OSM across various cancers is available, and the mechanisms behind OSM-related cancer progression remain to be elucidated. Methods: Based on the cancer genome atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we conducted a pan-cancer analysis on OSM to explore its tumor-related functions across cancers as well as its correlations with specific molecules, cells in tumor microenvironments. In addition, we chose the specific tumor glioblastoma multiforme (GBM) to screen out the OSM-induced signaling pathways and intercellular communication in tumor progression. Results: Higher OSM level was found in most tumor tissues compared with corresponding normal tissues, and the enhanced OSM expression was observed to be strongly related to patient poor prognosis in several cancers. Moreover, the expression of OSM was associated with stromal and immune cell infiltration in tumor microenvironments, and OSM-related immune checkpoint and chemokine co-expression were also observed. Our results suggested that OSM could communicate extensively with the tumor microenvironments. Taking GBM as an example, our study found that two critical signaling pathways in OSM-related tumor progression by KEGG enrichment analysis: Jak-STAT and NF-κB pathways. Single cell RNA sequencing data analysis of GBM also revealed that OSM was mainly secreted by microglia, and cell-cell interaction analysis proved that OSM-OSMR is an important pathway for OSM to stimulate malignant cells. Conclusion: Taken together, our study provides a comprehensive understanding with regard to the tumor progression under the regulation of OSM. OSM seems to be closely related to chronic inflammation and tumor development in the tumor microenvironment. As an important inflammatory factor in the tumor microenvironment, OSM may serve as a potential immunotherapeutic target for cancer treatment.