An Exploration of the Association of ZDHHC2 and ZDHHC15 with Various Cancers: Expression Profile and Prognostic Implications

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2025

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Saudi Digital Library

Abstract

S-Acylation is a post-translational modification that is essential for the function of many proteins, playing a key role in inflammation, cell proliferation, and signal transduction. This process is catalysed by the ZDHHC enzyme family, which has 23 members. Several studies have suggested their involvement in cancer development. This study aimed to investigate the association of ZDHHC2 and ZDHHC15 with various cancers. A bioinformatics approach was used to evaluate oncogenic and tumour-suppressive roles, gene expression, prognostic implications, genetic alterations, and protein interactions of these enzymes. IntOGen, COSMIC, UCSC Xena, cBioPortal, STRING, and BioGRID databases were used. The results showed that ZDHHC2 and ZDHHC15 were not classified as tumour drivers or suppressors. Gene expression of ZDHHC2 was significantly downregulated in several types of cancers, while ZDHHC15 was downregulated in all cancers tested, except for cholangiocarcinoma. Survival analysis showed ZDHHC2 and ZDHHC15 overexpression was associated with either better or worse prognosis depending on the cancer type. For ZDHHC2, deep deletion of the gene was seen in some cancer types and was associated with lower mRNA expression but not with changes in patient survival. Finally, BioGRID analysis revealed potential interactions of ZDHHC2 and ZDHHC15 with tumour drivers and tumour suppressors that may be relevant to their associations with cancer.

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S-Acylation, cancer, ZDHHC2, ZDHHC15

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