EGFR as a prognostic biomarker and therapeutic target in ovarian cancer: evaluation of patient cohort and literature review

Mehner, Christine; Oberg, Ann L.; Goergen, Krista M.; Kalli, Kimberly R.; Maurer, Matthew J.; Nassar, Aziza; Goode, Ellen L.; Keeney, Gary L.; Jatoi, Aminah; Radisky, Derek C.; Radisky, Evette S.

doi:10.18632/genesandcancer.142

Cited by 53 publications

(48 citation statements)

References 67 publications

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“…3 A). Furthermore, we found FBXL20 outperformed other potential OvCa prognostic molecular markers, including mutation status of BRAC1/2 [ 19 ] and TP53 [ 20 ], and expression levels of WTAP (Wilms' tumor 1-associating protein) [ 21 ] and EGFR [ 22 ] (Supplementary 4). We also found that FBXL20 expression levels and cellular protein levels do not correlate with OvCa staging, indicating FBXL20 can be an independent OvCa prognostic biomarker (Supplementary 5).…”

Section: Resultsmentioning

confidence: 99%

Age-related copy number variations and expression levels of F-box protein FBXL20 predict ovarian cancer prognosis

Zheng

2020

Translational Oncology

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About 70% of ovarian cancer (OvCa) cases are diagnosed at advanced stages (stage III/IV) with only 20–40% of them survive over 5 years after diagnosis. A reliably screening marker could enable a paradigm shift in OvCa early diagnosis and risk stratification. Age is one of the most significant risk factors for OvCa. Older women have much higher rates of OvCa diagnosis and poorer clinical outcomes. In this article, we studied the correlation between aging and genetic alterations in The Cancer Genome Atlas Ovarian Cancer dataset. We demonstrated that copy number variations (CNVs) and expression levels of the F-Box and Leucine-Rich Repeat Protein 20 ( FBXL20 ), a substrate recognizing protein in the SKP1-Cullin1-F-box-protein E3 ligase, can predict OvCa overall survival, disease-free survival and progression-free survival. More importantly, FBXL20 copy number loss predicts the diagnosis of OvCa at a younger age, with over 60% of patients in that subgroup have OvCa diagnosed at age less than 60 years. Clinicopathological studies further demonstrated malignant histological and radiographical features associated with elevated FBXL20 expression levels. This study has thus identified a potential biomarker for OvCa prognosis.

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Section: Resultsmentioning

confidence: 99%

Age-related copy number variations and expression levels of F-box protein FBXL20 predict ovarian cancer prognosis

Zheng

2020

Translational Oncology

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“…However, there is still some conflicting reports. For example, some data favored EGFR as a reliable marker of survival or responsiveness to therapy [ 18 , 19 ] but others did not [ 20 , 21 ], and some reports indicated that using EGFR inhibitors in ovarian cancer patient had not shown favorable clinical outcomes [ 15 , 22 , 23 ]. Thus, in this paper, it was investigated whether CHAG inhibited the development of ovarian cancer cells via abrogation of activation of EGFR and EGF/EGFR mediated signaling cascades.…”

Section: Resultsmentioning

confidence: 99%

Cross-linked hyaluronan gel inhibits the growth and metastasis of ovarian carcinoma

et al. 2018

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BackgroundThe recurrence, metastasis and poor prognosis are important characteristics of ovarian carcinoma (OC), which are associated with exfoliation of cells from the primary tumor and colonization of the cells in pelvic cavity. On the other hand, the life quality of the patients undergoing surgical resection of OC was influenced by postoperative adhesions. Therefore, preventing postoperative implant tumor and adhesion may be effective methods to improve OC treatment. HyaRegen Gel, a cross-linked hyaluronan gel (CHAG), has been widely used as an anti-adhesive agent following pelvic operation in clinic. However, whether it can affect the implantation and growth of OC cells or not is still not clear.MethodsMigration and invasion assays were applied to detect the effect of CHAG on migration and invasion of OC cells. Western blotting was performed to detect the phosphorylation/activation of EGFR and ERK, and the expression of PCNA and MMP7. Pull down assay was used to analyze the effect of CHAG on the activation of small G protein Rac1. Nude mice implantation tumor model was applied to observe the effect of CHAG on implantation tumor of OC cells.ResultsThe results of in vitro experiments showed that CHAG suppressed both basic and EGF-induced migration and invasion of OC cells, blocked the activation of EGF-initiated EGFR activation, inhibited downstream signal transduction of EGFR, and decreased expression of proliferation and migration/invasion related proteins. Meanwhile, results of in vivo experiments showed that CHAG not only inhibited the formation of implantation tumor of OC cells but also delayed the of the growth of the tumors.ConclusionsCHAG inhibited migration, invasion and proliferation of OC cells in vitro, and suppressed development of implantation tumor of OC in vivo. This made it as both anti-tumor and anti-adhesion agents.Electronic supplementary materialThe online version of this article (10.1186/s13048-018-0394-z) contains supplementary material, which is available to authorized users.

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“…Several studies examined the expression level of the individual member of the HER family in patients with ovarian cancer. The expression of EGFR, HER-2, HER-3 and HER-4 reported in the literature for ovarian cancer exhibits wide variation ranging from 9–90%, 6.4–52%, 16–69%, and 65–90% of the cases examined respectively, with EGFRvIII expression being rare [ 52 – 59 ]. In this study of 60 FIGO stage III and IV patients, the expression levels of the EGFR and HER-2 were determined by immunohistochemistry using mAb EGFR.113 and mAb 3B5 respectively.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, Mehner and colleagues reported the result of immunohistochemical staining of EGFR in tissue microarrays from 488 ovarian cancer patients. They found while 90% of their tumor specimens had some EGFR staining and 53% had membranous staining, the EGFR staining alone was not of prognostic value [ 59 ]. Also, there is currently conflicting data on the prognostic significance of CD44 in patients with ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Co-expression and prognostic significance of the HER family members, EGFRvIII, c-MET, CD44 in patients with ovarian cancer

et al. 2018

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EGFR and HER-2 are important targets but none of the monoclonal antibodies or small molecule tyrosine kinase inhibitors specific for the HER members has been approved for the treatment of patients with ovarian cancers. In some studies, co-expression of other growth factor receptors has been associated with resistance to therapy with the HER inhibitors. The aim of the present study was to determine the relative expression, cellular location, and prognostic significance of HER-family members, the EGFR mutant (EGFRvIII) c-MET, IGF-1R and the cancer stem cell biomarker CD44 in 60 patients with FIGO stage III and IV ovarian cancer. At cut off >5% of tumour cells with positive staining, 62%, 59%, 65% and 45% of the cases were EGFR, HER-2, HER-3 and HER-4 positive, and 3%, 22% and 48.3% of the cases were positive for EGFRvIII, c-MET, and CD44 respectively. Interestingly, 23% co-expressed all four members of the HER family. On univariate analysis, only EGFR staining at >50% of tumour cells (HR = 3.57, p = 0.038) and CD44 staining at 3+ intensity (HR = 7.99, p = 0.004) were associated with a poorer overall survival. EGFR expression (HR = 2.83, p = 0.019) and its co-expression with HER-2, HER-3, HER-2/HER-3, and c-MET were all associated with poorer disease-free survival. Our results suggest co-expression of the HER-family members is common in Stage III and IV ovarian cancer patients. Further studies on the prognostic significance and predictive value of all HER family member proteins for the response to treatment with various forms of the HER inhibitors are warranted.

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EGFR as a prognostic biomarker and therapeutic target in ovarian cancer: evaluation of patient cohort and literature review

Cited by 53 publications

References 67 publications

Age-related copy number variations and expression levels of F-box protein FBXL20 predict ovarian cancer prognosis

Age-related copy number variations and expression levels of F-box protein FBXL20 predict ovarian cancer prognosis

Cross-linked hyaluronan gel inhibits the growth and metastasis of ovarian carcinoma

Co-expression and prognostic significance of the HER family members, EGFRvIII, c-MET, CD44 in patients with ovarian cancer

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