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Integrated pan-cancer profiling and experimental validation identify CCDC59 as a key driver and therapeutic biomarker
Kun Li1, Dan Wan1, Xiao Liang1
1Department of General Surgery, National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Background:
CCDC59, a coiled-coil domain-containing (CCDC) family member, is involved in multiple diseases, yet its pan-cancer role remains largely unclear.
Methods:
We analyzed CCDC59 across cancers using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), along with R and tools like STRING, TISIDB, and TISCH2. CCDC59 expression was validated in clinical samples via quantitative real-time PCR (RT-qPCR) and western blot. Functional assays (proliferation, colony formation, and transwell) and cell cycle analysis were performed in liver hepatocellular carcinoma (LIHC) cells after siRNA-mediated CCDC59 knockdown.
Results:
CCDC59 was overexpressed in most cancers, particularly in bladder cancer. Its expression correlated positively with tumor mutational burden (TMB) in 21 cancer types and with microsatellite instability (MSI) in 24 cancer types, suggesting diagnostic potential. High CCDC59 expression was associated with poor prognosis and multiple clinicopathological features in renal papillary cell carcinoma (KIRP) and LIHC. Protein-protein interaction (PPI) and enrichment analyses linked CCDC59 and its co-expressed genes to pathways related to DNA damage, epithelial-mesenchymal transition (EMT), cell cycle, and immune infiltration, with prominent expression observed in B cells. CCDC59 also correlated with ferroptosis- and m6A-related genes in KIRP and LIHC and was predicted to interact with multiple molecules. Experimental validation in LIHC tissues confirmed elevated CCDC59 expression, and its knockdown inhibited proliferation, colony formation, migration, and invasion, while inducing G1 arrest and reducing S phase cells in HepG2 and Hep3B cells.
Conclusion:
CCDC59 is highly expressed in LIHC and other cancers, with potential diagnostic and prognostic value, and targeting it may improve immunotherapy and chemotherapy efficacy.
Data Availability:
The bioinformatics datasets used in this study are available at the corresponding websites, and raw data used during experiments will be made available by the authors upon reasonable request.
Insights
Coiled-coil domain-containing 59 (CCDC59) is overexpressed in most cancers, showing diagnostic and prognostic potential. Targeting CCDC59 may enhance immunotherapy and chemotherapy efficacy in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- The pan-cancer role of CCDC59, a coiled-coil domain-containing protein, is largely unknown.
- CCDC59 is implicated in various diseases, necessitating further investigation into its broader oncogenic functions.
Purpose of the Study:
- To elucidate the pan-cancer expression patterns of CCDC59.
- To investigate the diagnostic and prognostic significance of CCDC59 in various cancers.
- To explore the functional role of CCDC59 in liver hepatocellular carcinoma (LIHC).
Main Methods:
- Bioinformatic analysis of CCDC59 expression using TCGA, GEO, and HPA databases.
- Validation of CCDC59 expression in clinical samples via RT-qPCR and western blot.
- Functional assays including proliferation, colony formation, migration, invasion, and cell cycle analysis in LIHC cells following CCDC59 knockdown.
Main Results:
- CCDC59 is overexpressed in most cancers, correlating with tumor mutational burden (TMB) and microsatellite instability (MSI), indicating diagnostic potential.
- High CCDC59 expression is linked to poor prognosis and clinicopathological features in renal papillary cell carcinoma (KIRP) and LIHC.
- CCDC59 knockdown suppressed LIHC cell proliferation, migration, and invasion, and induced cell cycle arrest.
Conclusions:
- CCDC59 is significantly overexpressed in LIHC and other cancers, possessing diagnostic and prognostic value.
- CCDC59 plays a crucial role in cancer progression, particularly in LIHC.
- Targeting CCDC59 presents a potential strategy to improve the efficacy of immunotherapy and chemotherapy.
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