A pan-cancer portrait of PDK1: From oncogenic driver to context-dependent immunological regulator.

Despite being a well-established oncogenic regulator of metabolism promoting aerobic glycolysis, the pan-cancer prognostic value of PDK1, along with its immunomodulatory activity, is still poorly understood. In this research, an integrated multi-omics analysis was used to describe the expression of PDK1 and its prognostic role and immunomodulatory activity in different types of cancers, but specifically in kidney renal clear cell carcinoma (KIRC). It was found that PDK1 was overexpressed in various types of cancers, in which it always presented poor prognostic factors. Low PDK1 levels of tumors preserved an immunologically active microenvironment, and high PDK1 expression was recognized to be sensitive to chemotherapy and targeted agents. In KIRC, in particular, high PDK1 levels were linked to high TIL and PD-L1, which supports the idea that PDK1 is a combined immunological and prognostic biomarker. These results define the multifactorial functions of PDK1 in tumorigenesis and immunoregulation, which opens the path to the creation of PDK1-targeted therapies in clinical oncology.