Dataset Information

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma.

ABSTRACT:

Background

PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC.

Methods

We obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm to establish a PTEN mutation-associated prognostic gene signature. The overall survival rates of the high-risk and low-risk groups were determined with the Kaplan-Meier (K-M) method, and the accuracy of risk score prediction was tested by using the receiver operating characteristic (ROC) curve.

Results

The K-M curves revealed that the EC patients with PTEN mutations augured favorable survival outcomes. Differential expression analysis between the EC patients with PTEN mutation and wild-type PTEN identified 224 differentially expressed genes (DEGs). Eighty-four DEGs that manifested prognostic value were fitted into the LASSO-Cox analysis, and a PTEN gene signature with seven mutation-associated prognostic genes that showed robust prognostic ability was constructed; this signature was then successfully validated in the other two datasets from the cBioPortal database as well as with 60 clinical specimens. Furthermore, the PTEN mutation-associated prognostic gene signature proved to be an independent prognostic predictor of EC. Remarkably, the EC patients in the high-risk group were characterized by higher tumor stages and grades as well as lower tumor mutation burden with respect to EC, with a poor survival outcome. Collectively, the PTEN mutation-associated prognostic gene signature that we developed could now be used as a favorable prognostic biomarker for EC.

Conclusion

In summary, we developed and validated a prognostic predictor for EC associated with PTEN mutational status that may be used as a favorable prognostic biomarker and therapeutic target for EC.

SUBMITTER: Wu Y

PROVIDER: S-EPMC8890874 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma.

Wu Ying Y Wang Jun J Ge Lina L Hu Qing Q

Oxidative medicine and cellular longevity 20220223

<h4>Background</h4>PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC.<h4>Methods</h4>We obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least a ...[more]

PMID: 35251475

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Project description:BackgroundTP53 mutations are associated with poor outcome for patients with endometrial carcinoma (EC). However, to date, there have been no studies focused on the construction of TP53 mutational status-associated signature in EC. In this study, we aim to conduct a TP53 mutation-associated prognostic gene signature for EC.MethodsHence, we explored the mutational landscape of TP53 in patients with EC based on the simple nucleotide variation data downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and least absolute shrinkage and selection operator (LASSO)-Cox analysis was used to establish TP53 mutation-associated prognostic gene signature. The overall survival rate between the high-risk and low-risk groups was compared by the Kaplan-Meier (K-M) method.ResultsWe found that the TP53 mutation was associated with poor outcome, older age, lower BMI, and higher grade and stage of EC in patients. A TP53 mutational status-associated signature was established based on transcriptome profiling data. Moreover, the patients in TCGA database were categorized into high- and low-risk groups. Kaplan-Meier (K-M) analysis indicated that the patients in the high-risk group have poor survival outcome. Furthermore, receiver operating characteristic (ROC) curves confirmed the robust prognostic prediction efficiency of the TP53 mutational status-associated signature. Finally, the prognostic ability was successfully verified in the other two datasets from cBioPortal database as well as in 60 clinical specimens. Univariate (hazard ratio (HR) = 1.041, 95%CI = 1.031-1.051, p < 0.001) and multivariate (hazard ratio (HR) = 1.029, 95%CI = 1.018-1.040, p < 0.001) Cox regression analyses indicated that the TP53 mutational status-associated signature could be used as an independent prognostic factor for EC patients.ConclusionIn summary, our research constructed a powerful TP53 mutational status-associated signature that could be a potential novel prognostic biomarker and therapeutic target for EC.

Project description:BackgroundEndometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC.MethodsBased on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot.ResultsWe analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs.ConclusionsBTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.

Project description:BackgroundEndometrial cancer (EC) is one of the most common malignancies among women. To improve the prognosis and treatment of EC, finding out a phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-associated prognostic signature would be beneficial.MethodsEC clinical data, genetic mutation data, and transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. To clarify the specific PTEN-associated signature, cox regression analyses were performed. The clinical value of the selected signature on the overall survival (OS) and the secretoglobin family 2A member 1 (SCGB2A1)-independent analysis, immune and functional analysis were investigated respectively.ResultsFive hundred and fourteen EC samples were screened and PTEN mutation occupied 57%. Enrichment analysis indicated that mutant-type PTEN was enriched for pathways related to the upregulated human T-cell leukemia virus-1 (HTLV-1) infection and estrogen signaling pathway. SCGB2A1 was identified by cox regression analysis. Immune analysis exhibited significant immune infiltration with higher expression of T cells, B cells, and macrophage groups. Immune-checkpoint transcripts CD274 molecule (CD274), and cytotoxic T-lymphocyte associated protein 4 (CTLA4), hepatitis A virus cellular receptor 2 (HAVCR2), lymphocyte activation gene 3 (LAG3), programmed cell death 1 (PDCD1), PDCD1 ligand 2 (PDCD1LG2), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), and sialic acid binding immunoglobulin like lectin 15 (SIGLEC15) were discovered statistically different. In addition, the low-SCGB2A1 group had worse OS than the high-SCGB2A1 group. SCGB2A1 showed significant area under the curve (AUC) values in a time-dependent receiver operating characteristic (ROC) analysis. Prevalence of microsatellite instability (MSI) was detected and SCGB2A1 showed a negative correlation with EC. Immune checkpoint blockade (ICB) response indicated a worse immune response in the low-SCGB2A1 group. The distribution of one-class linear regression (OCLR) scores reflected the negative correlation between messenger RNA expression-based stemness index (mRNAsi) and prognostic gene expression. Furthermore, several SCGB2A1-related signaling pathways in EC were identified.ConclusionsSCGB2A1 is a prognostic immunometabolic signature for patients with EC, which may help improve the prognosis and therapeutic effect.

Dataset Information

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma.

Background

Methods

Results

Conclusion

Publications

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma.

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