The prognostic significance and potential mechanism of PFDN4 in hepatocellular carcinoma

PFDN4, a subunit of the prefoldin complex, has been previously shown to be upregulated in breast and colorectal cancers, where its expression correlates with poor clinical outcomes. This study investigates PFDN4 expression across various cancer types, with a specific focus on its role in hepatocellular carcinoma (HCC) development and progression. Analysis of TCGA data revealed that PFDN4 is highly expressed in several cancers and is associated with poor prognosis. Further validation through multiple databases, tissue microarrays, and clinical samples confirmed that PFDN4 protein levels are significantly elevated in HCC tissues. Meanwhile, multiple database multivariate and univariate Cox regression analyses suggest that PFDN4 is an independent prognostic marker for HCC. To evaluate the functional effects of PFDN4, we established stable HCC cell lines with PFDN4 knockdown and overexpression. Using CCK-8, EdU, wound healing, and Transwell assays, we found that PFDN4 knockdown significantly suppressed cell proliferation, migration, and invasion, while its overexpression enhanced these behaviors. These findings were further validated in vivo. Mechanistically, transcriptome sequencing suggested that PFDN4 modulates HCC cell behavior through the MAPK/ERK signaling pathway, a result confirmed by Western blot and the use of the MAPK/ERK inhibitor SCH772984. Additionally, single-cell RNA sequencing data revealed that PFDN4 is primarily expressed in several immune cell types, including B cells, CD8 + Tex, DC, ILC, mast cells, macrophages, Tprolif, and Treg. In conclusion, our study demonstrates that PFDN4 is upregulated in HCC and drives tumor progression via the MAPK/ERK pathway, highlighting its potential as both a prognostic marker and therapeutic target for HCC.