FOXA1 is expressed in ovarian mucinous neoplasms

Karpathiou, Georgia; Venet, Melany; Mobarki, Mousa; Forest, Fabien; Chauleur, Céline; Péoc’h, Michel

doi:10.1016/j.pathol.2016.11.009

Cited by 10 publications

(13 citation statements)

References 23 publications

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“…It was demonstrated that FOXA1 have a directly and/or indirectly role in the regulation of EMT occurrence. Our findings were consistent with the results in other research [ 41 , 42 ]. For example, Badve et al implied that the concentration of FOXA1 varied at different stages in the course of tumor progression with a significant correlation with drug resistance and poor prognosis in both breast and prostate tumors [ 30 ].…”

Section: Discussionsupporting

confidence: 94%

“…Activated CTGF/TGF- β pathway leads to a loss of adhesion between cells, accelerating the development of EMT and metastasis in tumors [ 47 ]. There are many researches on CTGF pointing out its direct or indirect role in facilitating tissue fibrosis or profibrotic TGF- β 1 activity [ 35 , 40 , 42 , 44 ]. Persistent activation of TGF- β pathway is associated with malignancies of cancers.…”

Section: Discussionmentioning

confidence: 99%

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Systematic Pan-Cancer Analysis and Experimental Verification Identify FOXA1 as an Immunological and Prognostic Biomarker in Epithelial Ovarian Cancer

Wang

Guan

et al. 2022

Disease Markers

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Background. Epithelial ovarian cancer (EOC) has the lowest survival rate among female reproductive cancers present with symptoms of aggressive malignancies, poor prognosis, drug resistance and postoperative recurrence. The majority of patients with EOC are diagnosed at an advanced stage due to the therapeutic challenges including lack of early diagnosis and effective therapeutic targets for EOC. Methods. Pan-cancer analyses were performed to explore the features of forkhead-box (FOX) A1 (FOXA1) using data from TCGA and GTEx databases. R package “clusterprofiler” was used to perform the enrichment analysis of FOXA1 in EOC. Data downloaded from Drug Sensitivity in Cancer (GDSC) database were used to evaluate the association between FOXA1 and antitumor drug sensitivity. In experimental verification, FOXA1 expression was detected using qRT-PCR and western blot assays. Western blot, immunofluorescence staining, and Transwell assays were used to assess the influence of FOXA1 silencing on epithelial-mesenchymal transition (EMT) of EOC cells. Results. We found that FOXA1 was highly expressed in EOC and predicted poorer survival of EOC patients. We observed that FOXA1 expression was positively correlated EMT-related pathways. Through experimental verification, we found the underlying function of FOXA1 to promote EMT in ovarian cancers. The results from western blot, immunofluorescence staining, and Transwell assays showed that FOXA1 silencing impeded the progression of EMT and invasiveness of the cancer cells. Furthermore, CCK-8 and invasion assays suggested that siRNA-FOXA1 attenuated the ability of cancer cells to metastasize and proliferate. Dual-luciferase reporter assays confirmed the binding activity of FOXA1 to the promoter of connective tissue growth factor (CTGF). In addition, we found that FOXA1 was closely correlated immunosuppressive microenvironment of EOC. High FOXA1 expression may contribute to the resistance of many anticancer drugs. Conclusions. Our results predict and validate the function of FOXA1 in promoting EMT and the progression of disease in EOC. Targeting FOXA1 may improve the sensitivity of EOC treatment.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Systematic Pan-Cancer Analysis and Experimental Verification Identify FOXA1 as an Immunological and Prognostic Biomarker in Epithelial Ovarian Cancer

Wang

Guan

et al. 2022

Disease Markers

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“…In the study by Karpathiou et al 21 , 19% of EOC strongly and diffusely expressed FOXA1and 75% of these EOC were of the mucinous followed by serous histology, but endometrioid and CCCs were completely negative. In agreement with the former study, 34.7% of our samples exhibited high FOXA1 expression and all mucinous carcinomas were in this category.…”

Section: Discussionmentioning

confidence: 91%

“…To the best of our knowledge, few previous studies have investigated FOXA1 expression in EOC 21-23 , with no certainty about the favorable versus unfavorable impact of FOXA1 expression on patients’ outcome and survival. In attempt to fill this gap, this study is addressed to assess the frequency of FOXA1 immunohistochemical (IHC) expression in EOC of different histopathologic types and to evaluate its associations with the clinico-pathological parameters in EOC including overall and disease-free survivals (OS and DFS respectively) and patient’s outcome.…”

Section: Introductionmentioning

confidence: 99%

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer

et al. 2021

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Summary Background Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC). Aim This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient’s outcome. Methods Patient’s socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis. Results FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor’s anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor’s anatomical extent and tumor’s size (p ≤ 0.001, = 0.046 and = 0.023 respectively). Conclusion FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

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“…FOXA1 can directly bind to the DNA and open the chromatin to enhance the transcription; so, it is described as a pioneer transcription activator [ 21 ]. It has been confirmed that FOXA1 is positively expressed in OC tissue, and it is involved in the pathogenesis and development of OC [ 22 ]. Endothelin receptor type B (EDNRB) is a member of the family of G-protein-coupled receptors, which plays a vital role in tumor cell proliferation, migration, and lymph angiogenesis via combination with endothelin-1 [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Autoantibodies against LRDD, STC1, and FOXA1 as Biomarkers in the Detection of Ovarian Cancer

et al. 2022

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Purpose. This study is aimed at evaluating serum autoantibodies against four tumor-associated antigens, including LRDD, STC1, FOXA1, and EDNRB, as biomarkers in the immunodiagnosis of ovarian cancer (OC). Methods. The autoantibodies against LRDD, STC1, FOXA1, and EDNRB were measured using an enzyme-linked immunosorbent assay (ELISA) in 94 OC patients and 94 normal healthy controls (NHC) in the research group. In addition, the diagnostic values of different autoantibodies were validated in another independent validation group, which comprised 136 OC patients, 136 NHC, and 181 patients with benign ovarian diseases (BOD). Results. In the research group, autoantibodies against LRDD, STC1, and FOXA1 had higher serum titer in OC patients than NHC ( P < 0.001 ). The area under receiver operating characteristic curves (AUCs) of these three autoantibodies were 0.910, 0.879, and 0.817, respectively. In the validation group, they showed AUCs of 0.759, 0.762, and 0.817 and sensitivities of 49.3%, 42.7%, and 48.5%, respectively, at specificity over 90% for discriminating OC patients from NHC. For discriminating OC patients from BOD, they showed AUCs of 0.718, 0.729, and 0.814 and sensitivities of 47.1%, 39.0%, and 51.5%, respectively, at specificity over 90%. The parallel analyses demonstrated that the combination of anti-LRDD and anti-FOXA1 autoantibodies achieved the optimal diagnostic performance with the sensitivity of 58.1% at 87.5% specificity and accuracy of 72.8%. The positive rate of the optimal autoantibody panel improved from 62.4% to 87.1% when combined with CA125 in detecting OC patients. Conclusion. Serum autoantibodies against LRDD, STC1, and FOXA1 have potential diagnostic values in detecting OC.

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FOXA1 is expressed in ovarian mucinous neoplasms

Cited by 10 publications

References 23 publications

Systematic Pan-Cancer Analysis and Experimental Verification Identify FOXA1 as an Immunological and Prognostic Biomarker in Epithelial Ovarian Cancer

Systematic Pan-Cancer Analysis and Experimental Verification Identify FOXA1 as an Immunological and Prognostic Biomarker in Epithelial Ovarian Cancer

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer

Serum Autoantibodies against LRDD, STC1, and FOXA1 as Biomarkers in the Detection of Ovarian Cancer

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