Expression profiling of 22 genes involved in the PI3K–AKT pathway identifies two subgroups of high-grade endometrial carcinomas with different molecular alterations

Catasús, Lluis; D’Angelo, Emanuela; Pons, Cristina; Espinosa, Íñigo; Prat, Jaime

doi:10.1038/modpathol.2010.44

Cited by 51 publications

(31 citation statements)

References 41 publications

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“…One such expression signature of activated PI3Kinase has been reported by Gustafson 148 , another by Catasus. 149 Integrated analyses of genome-wide expression and copynumber data suggest that activation of this PI3Kinase signature is associated with amplification of PIK3CA region, aggressive phenotype and poor survival for endometrial carcinomas. 96 Other genes active in regulation of this pathway are K-ras, HER2/neu, ER and PTEN.…”

Section: Ermentioning

confidence: 99%

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

Trovik

Mauland

Werner

et al. 2012

Gynecologic Oncology

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Section: Ermentioning

confidence: 99%

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

Trovik

Mauland

Werner

et al. 2012

Gynecologic Oncology

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“…A series of novel candidate prognostic markers 15, 16, 17, 18 have been discovered and confirmed to potentially improve the diagnosis and prognosis of EC. Prognostic models 7, 12, 19, 20 that aggregate several signature genes/proteins based on gene expression profiles or protein arrays also have been constructed, but these models are only effective for partial stages and/or grades of EC. Moreover, the developed prognostic signatures are difficult to apply widely.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a nine‐gene prognostic model for predicting overall survival of patients with endometrial carcinoma

Ying

Wang

et al. 2018

Cancer Medicine

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Endometrial carcinoma (EC) is the most common malignant tumor of the female genital tract in developed countries. The prognosis of early stage EC is favorable, but a subset faces high risk of cancer progression or recurrence. EC has a poor prognosis upon progression to advanced or metastatic stages. Therefore, our goal is to build a robust prognostic model for predicting overall survival (OS) in EC patients. In this study, 1571 genes were identified as being associated with OS based on genomewide expression profiles using a training dataset. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these genes were involved in various cancer‐related signaling pathways. Nine signature genes were further selected using stepwise selection, and their potential role in the development of EC was demonstrated by performing differential expression analysis between EC and normal uterine tissues. A prognostic model that aggregated these nine signature genes was ultimately established and effectively divided EC patients into two risk groups. OS for patients in the high‐risk group was significantly poorer compared with that of the low‐risk group. This nine‐gene model was subsequently validated and evaluated using the TCGA dataset and shown to have a high discriminating power to distinguish EC patients with an elevated risk of mortality based on the FIGO staging system and other prognostic factors. This study provides a novel prognostic model for the identification of EC patients with elevated risk of mortality and will help to improve our understanding of the underlying mechanisms involved in prognostic EC factors.

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“…Loss of tumor suppressor genes phosphatase and tensin homolog (PTEN), tuberous sclerosis complex 1,2 (TSC1 and TSC2), and LKB as well as activation mutations and/or amplification in oncogenes PI3K and AKT have been reported. [19][20][21][22][23] The PTEN gene encodes a phosphoinositide-3-phosphatase that antagonizes PI3K signaling through dephosphorylation of its intracellular second messenger, phosphoinositidyl-3 phosphate (PIP3) and serves as a major negative regulator of the PI3K/AKT signaling pathway 24 Loss of PTEN expression leads to deregulated activation of protein kinase B (PKB)/Akt signaling, an event that is thought to provide cells with a selective survival advantage by enhancing angiogenesis, protein translation, and cell cycle turnover.…”

Section: Journal Of Clinical Oncology O R I G I N a L R E P O R Tmentioning

confidence: 99%

Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group

Oza

Elit

Tsao

et al. 2011

JCO

311

185

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A B S T R A C T PurposePhosphatase and tensin homolog (PTEN) is a tumor suppressor gene, and loss of function mutations are common and appear to be important in the pathogenesis of endometrial carcinomas. Loss of PTEN causes deregulated phosphatidylinositol-3 kinase/serine-threonine kinase/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling which may provide neoplastic cells with a selective survival advantage by enhancing angiogenesis, protein translation, and cell cycle progression. Temsirolimus, an ester derivative of rapamycin that inhibits mTOR, was evaluated in this setting. Patients and MethodsSequential phase II studies evaluated single-agent activity of temsirolimus in women with recurrent or metastatic chemotherapy-naive or chemotherapy-treated endometrial cancer. Temsirolimus 25 mg intravenously was administered weekly in 4-week cycles. ResultsIn the chemotherapy-naive group, 33 patients received a median of four cycles (range, one to 23 cycles). Of the 29 patients evaluable for response, four (14%) had an independently confirmed partial response and 20 (69%) had stable disease as best response, with a median duration of 5.1 months (range, 3.7 to 18.4 months) and 9.7 months (range, 2.1 to 14.6 months). Only five patients (18%) had progressive disease. In the chemotherapy-treated group, 27 patients received a median of three cycles (range, one to six cycles). Of the 25 patients evaluable for response, one (4%) had an independently confirmed partial response, and 12 patients (48%) had stable disease, with a median duration of 4.3 months (range, 3.6 to 4.9 months) and 3.7 months (range, 2.4 to 23.2 months). PTEN loss (immunohistochemistry and mutational analysis) and molecular markers of PI3K/Akt/mTOR pathway did not correlate with the clinical outcome. Conclusion mTOR inhibition with temsirolimus has encouraging single-agent activity in endometrial cancer which is higher in chemotherapy-naive patients than in chemotherapy-treated patients and is independent of PTEN status. The difference in activity according to prior therapy should be factored into future clinical trial designs.

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Expression profiling of 22 genes involved in the PI3K–AKT pathway identifies two subgroups of high-grade endometrial carcinomas with different molecular alterations

Cited by 51 publications

References 41 publications

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

Establishment of a nine‐gene prognostic model for predicting overall survival of patients with endometrial carcinoma

Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group

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