Integrated Transcriptome and Multiple Activated Pathways in Endometrial Cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA754677 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15460373_1.fastq.gz | Fastqsanger.gz | |||
| SRR15460373_2.fastq.gz | Fastqsanger.gz | |||
| SRR15460374_1.fastq.gz | Fastqsanger.gz | |||
| SRR15460374_2.fastq.gz | Fastqsanger.gz |
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Project description:Because the incidence of endometrial cancer is notably increasing worldwide, it has become the leading gynecologic cancer in the United States. Standard treatment results in the loss of reproductive function in women of childbearing age. Furthermore, advanced cancer stages are associated with poor overall survival. The aim of this study was to explore the abnormal expression profile of genes during the development of endometrial cancer, which is essential to provide a better understanding of the mechanisms involved. Five pairs of endometrial cancer tissues and normal endometrial tissues were subjected to next-generation transcriptome sequencing technology. Quantitative real-time PCR (RT-qPCR) was performed to validate the expression profile of key differentially expressed genes (2.0-fold change, adj. p < 0.05) (DEGs) identified in the RNA-seq result. GO and KEGG pathways were used for bioinformatic analyses. The transcriptomic sequencing results showed 1153 DEGs, including 673 upregulated and 480 downregulated genes, in the EC specimens. Decreased expression of ID1, IGF1, GDF7, SMAD9, TGF-beta and WNT4, as well as GDF5, INHBA and ERBB4 overexpression, were confirmed in EC using RT-qPCR. Additionally, EC tissue exhibited marked enrichment in genes promoting cellular adhesion, proliferation, migration and plasma membrane. KEGG analysis revealed changes in various pathways, such as the TGF-beta, PI3K-Akt, Wnt, and estrogen pathways. Our data describe the molecular events involved in the pathogenesis of EC, which may be potential diagnostic markers and targets of therapeutic interventions.
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Project description:Because the incidence of endometrial cancer is notably increasing worldwide, it has become the leading gynecologic cancer in the United States. Standard treatment results in the loss of reproductive function in women of childbearing age. Furthermore, advanced cancer stages are associated with poor overall survival. The aim of this study was to explore the abnormal expression profile of genes during the development of endometrial cancer, which is essential to provide a better understanding of the mechanisms involved. Five pairs of endometrial cancer tissues and normal endometrial tissues were subjected to next-generation transcriptome sequencing technology. Quantitative real-time PCR (RT-qPCR) was performed to validate the expression profile of key differentially expressed genes (2.0-fold change, adj. p < 0.05) (DEGs) identified in the RNA-seq result. GO and KEGG pathways were used for bioinformatic analyses. The transcriptomic sequencing results showed 1153 DEGs, including 673 upregulated and 480 downregulated genes, in the EC specimens. Decreased expression of ID1, IGF1, GDF7, SMAD9, TGF-beta and WNT4, as well as GDF5, INHBA and ERBB4 overexpression, were confirmed in EC using RT-qPCR. Additionally, EC tissue exhibited marked enrichment in genes promoting cellular adhesion, proliferation, migration and plasma membrane. KEGG analysis revealed changes in various pathways, such as the TGF-beta, PI3K-Akt, Wnt, and estrogen pathways. Our data describe the molecular events involved in the pathogenesis of EC, which may be potential diagnostic markers and targets of therapeutic interventions.
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Project description:Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer. 84 endometrial cancers (including 9 cell lines) were subject to 100K SNP analysis. 57 endometrial cancers were subject to expression analysis.
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