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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
[Screening and identification of ovarian carcinomas related genes]
Wen Yue1, Li-Ya Sun, Chun-Hai Li
1Department of Stem Cell Biology, Beijing Institute of Transfusion Medicine, Beijing, PR China. yuewen@263.net
Background & Objective:
Ovarian cancer is the leading cause of death among gynecological malignancies. Up to now, little is known about specific tumor-suppressor genes or oncogenes involved in the ovarian cancer genesis. Thus isolation of new candidate genes and characterization of their role in ovarian cancer genesis will be helpful for understanding the molecular mechanisms and developing protocols for early diagnosis and therapy of ovarian carcinomas. This study was developed to screen and identify genes related to ovarian carcinomas.
Methods:
Modified mRNA differential display PCR and reverse Northern dot blot analysis were used to screen and identify different displayed genes between ovarian carcinoma tissue and normal ovarian tissue. The genes were sequenced and analyzed by bioinformatics software. With these gene fragments as probes, in situ hybridization was used to characterize specific gene expression difference between ovarian cancer tissues and normal ovarian tissues.
Results:
Of 12 differentially expressed genes, 5 were novel genes, 3 were chromosome genomic repeat sequences and the other 4 were known human genes. Furthermore, in situ hybridization analysis indicated that four genes, ZNF361, PSMA2, OCRC13 (a novel gene on chromosome 1) and OCRC4 (a novel gene on chromosome 9) were highly expressed in 36 samples of ovarian cancer tissues but not in 16 samples of normal ovarian tissues (P< 0.05). More interestingly, the gene OCRC4, with 99% sequence homology to mouse spindlin, a member of gene family specially expressed during gametogenesis, was highly expressed in 19 samples of ovarian cancer from total 36 cases (53%), but not expressed in control samples.
Conclusion:
Our observations indicate that the four genes ZNF361, PSMA2, OCRC4, and OCRC13 may be ovarian cancer related genes. It is speculated that novel gene OCRC4 might also be a member of specific gene family, which plays roles during early period of embryo development and tumorigenesis.
Insights
Researchers identified four key genes, including novel candidates OCRC4 and OCRC13, that are highly expressed in ovarian cancer tissues. These findings advance understanding of ovarian cancer development and potential diagnostic markers.
Area of Science:
- Genomics
- Molecular Oncology
- Gene Expression Profiling
Context:
- Ovarian cancer is a leading cause of gynecological cancer mortality.
- Understanding the genetic basis of ovarian cancer is crucial for developing effective diagnostics and therapies.
- Specific oncogenes and tumor-suppressor genes involved in ovarian cancer genesis remain largely unknown.
Purpose:
- To screen and identify novel genes associated with ovarian carcinoma.
- To characterize the differential expression of candidate genes between ovarian cancer and normal tissues.
- To explore the potential role of identified genes in ovarian cancer development.
Summary:
- Differential display PCR and reverse Northern dot blot analysis identified 12 differentially expressed genes between ovarian carcinoma and normal ovarian tissues.
- Four genes—ZNF361, PSMA2, OCRC13 (novel), and OCRC4 (novel)—showed significantly higher expression in ovarian cancer tissues.
- OCRC4, highly homologous to mouse spindlin, was overexpressed in 53% of ovarian cancer samples and absent in normal tissues.
Impact:
- Identified ZNF361, PSMA2, OCRC4, and OCRC13 as potential ovarian cancer-related genes.
- The novel gene OCRC4 may play a role in early embryonic development and tumorigenesis.
- These findings contribute to understanding ovarian cancer molecular mechanisms and may aid in early diagnosis and targeted therapy development.
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