EphA8 is a prognostic marker for epithelial ovarian cancer

Liu, Xiaoqin; Xu, Yunzhao; Jin, Qin; Wang, Wei; Zhang, Shu; Wang, Xudong; Zhang, Yuquan; Xu, Xujuan; Huang, Jianfei

doi:10.18632/oncotarget.8018

Cited by 20 publications

(21 citation statements)

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“…Patients only diagnosed as either TNM stage II or stage III OTSCC were enrolled in our study, for, on one hand, there is a very limited number of patients who were diagnosed as OTSCC at very early stage (stage I); on the other hand, patients at TNM stage IV have a very poor prognosis, making it hard to conduct a follow-up study. By examining the mRNA levels of EphA8 in fresh OTSCC tissues and adjacent non-tumor tissues, we found that EphA8 was highly expressed in OTSCC tissues comparing with non-tumor tissues, which was consistent with findings from an epithelial ovarian cancer study [ 20 ]. Furthermore, we also detected the differential expressions of EphA8 in different stages of OTSCC by performing IHC staining.…”

Section: Discussionsupporting

confidence: 87%

“…Ephs are the largest subfamily of RTKs and have been showed to be implicated in many aspects of cancer [ 28 , 29 ]. In this study, we focused on one of the receptors in the Ephs RTKs subfamily, EphA8, which has been reported to be pivotal in epithelial ovarian cancer [ 20 ]. In order to figure out the potential effects of EphA8 in OTSCC, we enrolled a total of 119 OTSCC patients and performed a retrospective study.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to tumor size, high EphA8 expression was also shown to be an independent prognostic factor for OTSCC by multivariate Cox proportional hazards regression model. Of note, EphA8 has been reported to be an independent prognostic factor in epithelial ovarian cancer [ 20 ]. It is thus of great value to explore whether EphA8 overexpression is a common process or mechanism in the progression of certain cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a cancer study reported that miR-10a/EphA8 pathway regulates epithelial-mesenchymal transition to affect cell migration and invasion [ 19 ]. Of note, EphA8 has been found highly expressed in epithelial ovarian cancer tissues compared to normal ovarian tissues; and high EphA8 protein level has been shown to be an independent prognostic factor in epithelial ovarian cancer [ 20 ]. However, so far, there is no study focusing on the role of EphA8 in the progression and prognosis of OTSCC.…”

Section: Introductionmentioning

confidence: 99%

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EphA8 is a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma

Liu

2018

Med Sci Monit

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BackgroundOral tongue squamous cell carcinoma (OTSCC) is the most common malignancy of the oral cavity. Here we explore the potential effects of EphA8, which is one of the receptors in Ephs subfamily of RTKs (receptor tyrosine kinases), in the progression and prognosis of OTSCC.Material/MethodsA total of 119 OTSCC patients were enrolled in this retrospective study. Immunohistochemistry (IHC) staining and quantitative polymerase chain reaction (Q-PCR) were utilized to examine the expression of EphA8 in OTSSC tissues and adjacent non-tumor tissues. The relationship between EphA8 expression and the clinicopathological features of OTSCC patients were analyzed by chi-square. Survival analysis was carried out with Kaplan-Meier curve and the related log-rank test. Multivariate analysis was then undertaken to assess the prognosis factor by utilizing the Cox proportional hazard regression model. In addition, MTT assay and Matrigel invasion assay were performed to examine the effects of EphA8 on the proliferation and invasion capacities of human oral squamous carcinoma cells (SCC-25) and human tongue squamous cell carcinoma cells (H357).ResultsQ-PCR and IHC staining revealed that EphA8 was highly expressed in OTSCC tissues, especially in advanced stage OTSCC tissues. Kaplan-Meier curve showed that high EphA8 expression was significantly associated with poor prognosis, similar to age, smoking habit, drinking habit, tumor size, and TNM stage. Multivariate analysis indicated that EphA8 expression could serve as an independent prognostic factor in OTSCC. In vitro experiments revealed that overexpression of EphA8 might promote the progression of OTSCC via enhancing the invasion capacity but not proliferation capacity of tumor cells.ConclusionsEphA8 was highly expressed in OTSCC tissues and was significantly associated with poor prognosis of OTSCC.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EphA8 is a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma

Liu

2018

Med Sci Monit

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“…Although the role of EPHA8 in cancer stem cells remains elusive, its overexpression correlates to a poor overall survival in other human malignancies, such as epithelial ovarian cancer (EOC) (24)(25)(26). In EOC, both EPHA8 and ephrin-A5 are significantly up-regulated (24), while only EPHA8 was reported to be overexpressed in OTSCC and GC (25).…”

Section: Discussionmentioning

confidence: 99%

Stem-like Cells from Invasive Breast Carcinoma Cell Line MDA-MB-231 Express a Distinct Set of Eph Receptors and Ephrin Ligands

Lucero

Thind

Sandoval

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Breast cancer cell lines consist of bulk tumor cells and a small proportion of stem-like cells. While the bulk cells are known to express a distinct combination of Eph receptors and ephrin ligands, the transcript profiles of stem-like cells in these cell lines have not been adequately characterized. The aim of this study was to determine Eph receptor/ephrin ligand profiles of cancer stem cells specific to a triple negative breast carcinoma cell line. Materials and Methods: The normal breast cell line MCF10A and the invasive breast carcinoma cell line MDA-MB-231 were used to isolate CD24 + /CD24cell populations. The profiles of Eph receptors and ephrin ligands were determined by real-time PCR and the relative abundance in bulk and stem cells were compared. Results: Based on the mean ∆CT values, the descending order of abundance was as follows. Ephrin-A5 > EPHA2 > (EPHA8, EPHB2) > ephrin-B2 > (EPHA7, EPHB4, ephrin-A4) > ephrin-A3 > ephrin-A1 > (EPHB3, ephrin-B1) > EPHA4 > EPHA1 > EPHA10. EPHA6 and ephrin-A2 transcripts were not detectable in stem cells from either cell line. The expression of EPHA4, EPHA7, EPHA8, and ephrin-A5 in MDA-MB-231 stem cells was up-regulated by 12, 20, ~500, and 6.5-fold respectively. Conclusion: The up-regulation of transcripts for EPHA8 and its cognate ligand, ephrin-A5, in the stem cells isolated from MDA-MB-231, suggest their involvement in the invasiveness of this cell line. Based on literature reports, we propose the role of EPHA8 and ephrin-A5 in MDA-MB-231 stem cells via the PI3K-AKT-mTOR pathway.

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EphA8 acts as an oncogene and contributes to poor prognosis in gastric cancer via regulation of ADAM10

Wang

Zhou

et al. 2019

Journal Cellular Physiology

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EphA8 is a member of the erythropoietin-producing hepatocellular receptor (Eph) family of receptor tyrosine kinases. Ephs and their ephrins ligands play crucial roles in many cellular processed by mediating intracellular signaling resulting from cell-cell interactions. But the underlying mechanisms of EphA8 in gastric cancer (GC) remains unclearly. 298 clinical specimens in tissues microarray, and was found to be significantly higher in GC tissues compared with nontumor tissues (p < 0.001). EphA8 expression was also strongly associated with differentiation level (p = 0.025), tumornode-metastasis stage (p = 0.019), and poor 5 years survival (p < 0.001). A panel of GC cell lines showed reduced proliferation, invasion, and migration capacities after RNAmediated knockdown of EphA8, concomitant with downregulation of the proliferation-related proteins (cyclin A, cyclin D1, and cyclin-dependent kinase 4) and the metastasis-related (matrix metalloproteinases MMP2, and MMP9). EphA8 knockdown also decreased expression of the protease ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) and ADAM10-related protein AKT, suggesting an interaction between EphA8 and ADAM10. In conclusion, we found that EphA8, which is highly expressed in GC tissues, stimulates proliferation, invasion, and migration of cancer cells, and is an independent risk factor for poor prognosis of GC.These dates suggest that EphA8 could be new diagnostic and/or therapeutic targets for GC.

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EphA8 is a prognostic marker for epithelial ovarian cancer

Cited by 20 publications

References 50 publications

EphA8 is a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma

EphA8 is a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma

Stem-like Cells from Invasive Breast Carcinoma Cell Line MDA-MB-231 Express a Distinct Set of Eph Receptors and Ephrin Ligands

EphA8 acts as an oncogene and contributes to poor prognosis in gastric cancer via regulation of ADAM10

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