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Background Growth/differentiation factor 15 (GDF15) is a member of the TGF-b superfamily whose expression is increased in response to cellular stress and disease. Although emerging cell-or animal-based evidence supports the relationship between GDF15 and cancers, systematic pan-cancer analysis of GDF15 remains unavailable. Thus, we aimed to explore the prognostic and immunological roles of GDF15 across different types of tumors. Methods A comprehensive analysis of GDF15 in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, immune infiltration analysis, potential biological pathways. Moreover, both the gain and loss of function strategies were used to assess the function of GDF15 in cell lines of hepatocellular carcinoma (HCC). Results GDF15 is highly expressed in most types of cancers, and there is a significant correlation between the expression of GDF15 and the prognosis of cancer patients. We have observed that GDF15 promotes the proliferation and invasion of HCC cell lines. Subsequently, methylation analyses suggested that high GDF15 expression likely resulted from hypomethylation, and immune infiltration analysis showed that GDF15 may have an impact on the changes in the tumor microenvironment. Moreover, enrichment analysis revealed that TGF-beta signaling and metabolism pathways were involved in the functional mechanisms of GDF15. Conclusions Our unpresented pan-cancer analysis of GDF15 offers a relatively comprehensive overview of the oncogenic roles of GDF15 in multiple human cancers. GDF15 may prompt HCC cellular proliferation, invasion and metastasis. All of these provides solid basement and will promote more advanced understanding the role of GDF15 in tumorigenesis and development from the perspective of clinical tumor samples and cells.

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