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PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.

ABSTRACT: Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways-either via mutations or genomic amplification-confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of PIK3CA in aggressive cancers, most of the available data highlight the important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways are investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of PI3K/AKT/mTOR pathways in major cancer types and examines its association with clinicopathological parameters and prognosis.

SUBMITTER: Alqahtani A

PROVIDER: S-EPMC7017171 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.

Alqahtani Ali A Ayesh Hazem S K HSK Halawani Hafez H

Cancers 20191230 1

Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways-either via mutations or genomic amplification-confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the <i>PIK3CA</i> gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of ...[more]

PMID: 31905960

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Project description:Aim of the studyThe FJ 194940.1 gene is located on chromosome 1 and consists of 6 exons and 5 introns. The gene undergoes alternative splicing and its isoforms appear during cancer development. Evidence suggests that expression of FJ 194940.1 splice variants relate to colorectal cancer progression. This paper discusses the quantitative analysis of the exon V expression level of FJ 194940.1 in colon cancer. The aim of the study is to carry out quantitative analysis by real-time PCR in a series of 102 colon cancer samples that had previously shown presence of exon V expression. To compare the exon V expression level with certain histological parameters and clinical staging of the neoplasm in order to assess its potential role as a prognostic factor in colon cancer.Material and methodsTissue specimens of colorectal cancer were obtained from the Oncological Centre of Lodz, Poland.Total RNA isolation was performed in accordance with the protocol enclosed in the Total RNA Prep Plus Minicolumn Kit (A&A Biotechnology, Poland). Reverse Transcriptase-PCR reaction was carried out using Enhanced Avian HSRT-PCR Kit, Sigma, according to the manufacturer's protocol.. Presence of cDNA in each sample was checked by PCR amplification of β-actin. Only samples showing the PCR product of this housekeeping gene were included in further tests. The amount of FJ 194940.1 transcript containing exon V was analysed by means of real-time PCR.ResultsExon V expression level is not significantly related to any clinicopathological features in colon cancer. However, there was a tendency towards a lower exon V expression level in a group of cases where vessel invasion was present (p = 0.0697). Additionally, the risk of death in patients with a low exon V expression level was more than two times higher when compared to patients with a high exon V expression level.ConclusionsFJ 194940.1 gene expression correlates with cancer progression independently of analysed clinicopathological parameters.

Dataset Information

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.

Publications

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.

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