Abstract
ZDHHC-protein acyltransferases (ZDHHCs) are a family of 23 signature Asp-His-His-Cys (DHHC) domain-containing enzymes that mediate palmitoylation by covalent attachment of the 16-carbon fatty acid palmitate to thiol groups of specific cysteine residues in substrate proteins. Emerging evidence has shown abnormal expression of ZDHHCs in a variety of disease states, including cancer. Kidney renal clear cell carcinoma (KIRC) is the eighth most common type of cancer, which accounts for the majority of malignant kidney tumors. However, there are currently no effective therapeutic targets or biomarkers for clinical treatment and prognosis in KIRC. In this study, we first analyzed the expression pattern of the 23 ZDHHCs in KIRC using TCGA and GEPIA database, and found that the expression of ZDHHC2, 3, 6, 14, 15, 21, and 23 was significantly down-regulated whereas the expression of ZDHHC9, 17, 18, 19 and 20 was significantly up-regulated in KIRC patient tissues vs. normal tissues. And the expression of ZDHHC2, 3, 6, 9, 14, 15, and 21 in tumors decreased with the increase of the pathological stage of KIRC patients. Notably, KIRC patients with decreased expression of ZDHHC3, 6, 9, 14, 15, 17, 20, 21, 23 and increased expression of ZDHHC19 were significantly associated with poor prognosis. Further, we found that there was a significant correlation between ZDHHC3, 6, 9, 14, 15, 17, 19, 20, 21, 23 expressions and immune cell infiltration. Besides, high mRNA expression was the most common type of gene alteration and there was a high correlation among the expression of ZDHHC6, 17, 20 and 21. Finally, function prediction indicated that the immune or metabolic disorders or the activation of oncogenic signaling pathways caused by abnormal expression of these ZDHHCs may be important mechanisms of tumor progression and poor prognosis in patients with KIRC. Our results may provide novel insight for identifying tumor markers or molecular targets for the treatment of KIRC.
Highlights
Kidney renal clear cell carcinoma (KIRC) is one of the eight most common cancer types, accounting for 70%–80% of renal cell carcinoma [1]
RNA-Seq data of ZDHHC-protein acyltransferases (ZDHHCs) in 538 kidney renal clear cell carcinoma (KIRC) tissue samples and 72 normal kidney tissue samples were extracted from The Cancer Genome Atlas (TCGA) database for gene expression analysis and gene set enrichment analysis (GSEA)
After further excluding ZDHHC16 and that had no significant difference in expression, we determined the expression of ZDHHC2, 3, 6, 14, 15, 21, and was significantly down-regulated whereas the expression of ZDHHC9, 17, 18, 19, and 20 was significantly up-regulated in KIRC patient tissues vs. normal tissues
Summary
Kidney renal clear cell carcinoma (KIRC) is one of the eight most common cancer types, accounting for 70%–80% of renal cell carcinoma [1]. Breakthroughs have been made in the molecular mechanisms and treatment strategies for KIRC in recent years, the prognosis of KIRC patients is still poor, especially for patients with the late clinical stage [3]. Studies show that patients with stage I KIRC have a five-year disease-specific survival of about 80%–95%, whereas the five-year diseasespecific survival rate of patients with IV KIRC drops sharply to less than 10% [4]. The low expression of ZDHHC2 in hepatocellular carcinoma was closely related to poor over survival and disease-free survival of patients [8]. Elevated expression of ZDHHC3 correlated with enhanced carcinoma growth and diminished patient survival in breast cancer [9]. Decreasing ZDHHC20 expression increases tumor cell sensitivity to EGFR tyrosine kinase inhibitors [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
