Pan-Cancer Analysis Reveals the Potential of PLOD1 as a Prognostic and Immune Biomarker for Human Cancer

<b>Background/Objectives:</b> Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is known as an enhancer of collagen fiber deposition and cross-linking stability. However, there is limited information on its function in tumors. In this study, we aimed to elucidate the function and potential mechanism of action of PLOD1 across cancers. <b>Methods:</b> We assessed the pan-cancer expression, mutation, methylation and prognostic value of PLOD1 through multiple online databases. In addition, we performed correlation analyses of its immunological features, as well as functional assessment analyses of PLOD1. Finally, we assessed the effect of PLOD1 knockdown on bladder tumor cells using in vitro experiments. <b>Results:</b> Our findings suggest that PLOD1 is aberrantly expressed in multiple cancer types, accompanied by a poor prognosis. Epigenetic alterations in PLOD1 are highly heterogeneous across a wide range of tumors, and aberrant methylation and copy number variants correlate with a poor prognosis. In the tumor microenvironment, PLOD1 expression correlated positively with the infiltration level of various immunosuppressive cells (e.g., monocytes, macrophages and tumor-associated fibroblasts) and negatively with immune-killing cells (e.g., CD8⁺ T cells, B cells and CD4⁺ T cells). In addition, PLOD1 expression was associated with immune checkpoints and immunomodulatory genes. Finally, in vitro experiments demonstrated that knockdown of PLOD1 reduced the proliferation, migration and antiapoptotic abilities of T24 cells. <b>Conclusions:</b> The results of this study demonstrate that PLOD1 is a potential oncogene and prognostic biomarker in pan-cancer; tumor tissues with high PLOD1 expression reveal a relatively immunosuppressive tumor microenvironment.