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Downregulation of the Coiled-Coil Domain Containing 80 and Its Perspective Mechanisms in Ovarian Carcinoma: A
Zi-Qian Liang1, Li Gao1, Jun-Hong Chen2
1Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6. Shuangyong Rd, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Introduction:
We aimed to explore the downregulation of the coiled-coil domain containing 80 (CCDC80) and its underlying molecular mechanisms in ovarian carcinoma (OVCA). Materials/Methods. Immunohistochemical staining was performed to confirm the expression status of CCDC80 protein. Combining the data from in-house tissue microarrays and high-throughput datasets, we identified the expression level of CCDC80 in OVCA. We utilized cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between CCDC80 and the tumor microenvironment (TME) landscape in OVCA. Pathway enrichment, function annotation, and transcription factor (TFs) exploration were conducted to study the latent molecular mechanisms. Moreover, the cell line data in the Genomics of Drug Sensitivity in Cancer (GDSC) database was used to discover the relationship between CCDC80 and drug sensitivity.
Results:
An integrated standard mean difference (SMD) of -0.919 (95% CI: -1.515-0.324, P = 0.002) identified the downregulation of CCDC80 in OVCA based on 1048 samples, and the sROC (AUC = 0.76) showed a moderate discriminatory ability of CCDC80 in OVCA. The fraction of infiltrating naive B cells showed significant differences between the high- and low-CCDC80 expression groups. Also, CCDC80-related genes are enriched in the Ras signaling pathway and metabolic of lipid. Nuclear receptor subfamily three group C member 1 (NR3C1) may be an upstream TF of CCDC80, and CCDC80 may be related to the sensitivity of mitocycin C and nilotinib.
Conclusion:
CCDC80 was downregulated in OVCA and may play a role as a tumor suppressor in OVCA.
Insights
Coiled-coil domain containing 80 (CCDC80) is downregulated in ovarian carcinoma (OVCA), suggesting its potential role as a tumor suppressor. Further research is needed to understand its molecular mechanisms and therapeutic implications in OVCA.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian carcinoma (OVCA) is a significant global health concern.
- Understanding the molecular mechanisms of OVCA is crucial for developing effective treatments.
- The role of coiled-coil domain containing 80 (CCDC80) in OVCA remains largely unexplored.
Purpose of the Study:
- To investigate the expression status of CCDC80 in OVCA.
- To elucidate the underlying molecular mechanisms associated with CCDC80 downregulation in OVCA.
- To explore the relationship between CCDC80, the tumor microenvironment (TME), and drug sensitivity in OVCA.
Main Methods:
- Immunohistochemical staining to assess CCDC80 protein expression.
- Analysis of high-throughput datasets and in-house tissue microarrays for CCDC80 expression levels.
- Application of CIBERSORT and ssGSEA algorithms to explore CCDC80's correlation with TME components.
- Pathway enrichment, function annotation, and transcription factor (TF) analysis to identify molecular mechanisms.
- Utilizing the Genomics of Drug Sensitivity in Cancer (GDSC) database to assess CCDC80's impact on drug sensitivity.
Main Results:
- CCDC80 was found to be significantly downregulated in OVCA (SMD = -0.919, P = 0.002) with moderate discriminatory ability (AUC = 0.76).
- Significant differences in naive B cell infiltration were observed between high- and low-CCDC80 expression groups.
- CCDC80-related genes are enriched in the Ras signaling pathway and lipid metabolism.
- Nuclear receptor subfamily 3 group C member 1 (NR3C1) may act as an upstream TF for CCDC80.
- CCDC80 expression may influence sensitivity to mitomycin C and nilotinib.
Conclusions:
- CCDC80 is downregulated in OVCA, indicating its potential role as a tumor suppressor.
- CCDC80 may influence the tumor microenvironment, particularly B cell infiltration.
- CCDC80's molecular pathways and its association with drug sensitivity warrant further investigation for therapeutic strategies in OVCA.
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