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Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer.

ABSTRACT: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is expressed in most human cell types (example: Epithelial cells, fibroblasts and endothelial), it serves a key role in the control of cell survival, proliferation and motility. The abnormal expression of FAK has been associated with poor prognosis in cancer, including ovarian cancer. However, although FAK isoforms with specific molecular and functional properties have been characterized, there are a limited number of published studies that examine FAK isoforms in ovarian cancer. The aim of the present study was to analyze the expression level of FAK and its isoforms in ovarian cancer. The expression of FAK kinase and focal adhesion targeting (FAT) domains was determined with immunohistochemistry in healthy ovary, and serous and mucinous cystadenoma, borderline tumor and carcinoma samples. Additionally, the expression of FAK and its isoforms were investigated in three ovarian cancer-derived cell lines with western blotting and reverse transcription-semi-quantitative polymerase chain reaction. An increased expression of FAK kinase domain was determined in serous tumor samples and was associated with advancement of the lesion. FAK kinase domain expression was moderate-to-low in mucinous tumor samples. The expression of the FAK FAT domain in tumor samples was reduced, compared with healthy ovary samples; however, the FAT domain was localized to the cellular nucleus. Expression of alternative transcripts FAK°, FAK28,6 and FAK28 was determined in all three cell lines investigated. In conclusion, FAK kinase and FAT domains are differentially expressed among ovarian tumor types. These results indicated the presence of at least two isoforms of FAK (FAK and the putative FAK-related non-kinase) in tumor tissue, which is supported by the cells producing at least three FAK alternative transcripts. These results may support the use of FAK and its isoforms as biomarkers for ovarian cancer.

SUBMITTER: Nolasco-Quiroga M

PROVIDER: S-EPMC6507456 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer.

Nolasco-Quiroga Manuel M Rosas-Díaz Marisol M Moreno José J Godínez-Aguilar Ricardo R López-Ibarra María José MJ Piña-Sánchez Patricia P Alvarado-Cabrero Isabel I Vázquez-Gómez Gerardo G Rocha-Zavaleta Leticia L Arenas-Aranda Diego D Salamanca-Gómez Fabio F

Oncology letters 20190315 6

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is expressed in most human cell types (example: Epithelial cells, fibroblasts and endothelial), it serves a key role in the control of cell survival, proliferation and motility. The abnormal expression of FAK has been associated with poor prognosis in cancer, including ovarian cancer. However, although FAK isoforms with specific molecular and functional properties have been characterized, there are a limited number of published s ...[more]

PMID: 31186683

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Project description:BackgroundOvarian cancer is a common gynecological malignant tumor that greatly threatens women's health, so we screened potential biomarkers of ovarian cancer and analyzed their prognostic value.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the ovarian cancer-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of ovarian cancer-related genes. The survival-related genes were screened out through the least absolute shrinkage and selection operator (LASSO) method. Multivariate Cox regression model and stepwise regression analysis were performed to construct the risk model. The receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to evaluate the prediction accuracy of risk score model. Finally, gene set enrichment analysis (GSEA) and immune cell infiltration analysis were performed to investigate the biological function and immune cell infiltration.ResultsA total of 111 genes were found to have common effects on survival. These genes were mainly involved in metabolism, protein phosphorylation and immune-related signaling pathways. Seven risk genes (AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1, ZNF426) were screened out. Among these genes, AP3D1 and LRFN4 are risk genes and DCAF10, FBXO16, PTPN2, SAYSD1, and ZNF426 are protective genes. These findings suggest that risk status may be an independent prognostic factor. The risk score had a high predictive value for the prognosis of ovarian cancer. In addition, GSEA revealed that the biological function of genes expressed in patients at a high risk was mostly related to immune-related function. The contents of CD4+ T cells, macrophages, myeloid dendritic cells (mDC) and neutrophils were high in samples at a high risk for ovarian cancer.ConclusionsThe abnormal expression of AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1 and ZNF426 is highly related to the progression of ovarian cancer. These seven genes can be used as independent prognostic markers of ovarian cancer. This study not only adds evidence to the pathogenesis of ovarian cancer but also provides scientific basis for judging the prognosis of ovarian cancer.

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Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer.

Publications

Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer.

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