Claudin-1 is linked to presence of implants and micropapillary pattern in serous borderline epithelial tumours of the ovary

El‐Balat, Ahmed; Schmeil, Iryna; Gasimli, Khayal; Sänger, Nicole; Karn, Thomas; Ahr, A.; Becker, Sven; Arsenić, Ruža; Holtrich, Uwe; Engels, Knut

doi:10.1136/jclinpath-2018-205292

Cited by 6 publications

(4 citation statements)

References 37 publications

(18 reference statements)

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“…Extensive studies conducted and analyzed for the association of CLDN-1 with survival and anatomical site showed 85% elevation of CLDN-1 expression [58]. Recently, the level of CLDN-1 expression was also investigated in borderline tumors of the ovary (BOT) [53]. A significantly higher level of CLDN-1 expression was associated with the peritoneal implants and micropapillary patterns that are specifically seen only in serous BOT [53].…”

Section: Claudin-1 and Ovarian Cancermentioning

confidence: 99%

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Claudin-1, A Double-Edged Sword in Cancer

Bhat

Syed

Therachiyil

et al. 2020

IJMS

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Claudins, a group of membrane proteins involved in the formation of tight junctions, are mainly found in endothelial or epithelial cells. These proteins have attracted much attention in recent years and have been implicated and studied in a multitude of diseases. Claudins not only regulate paracellular transepithelial/transendothelial transport but are also critical for cell growth and differentiation. Not only tissue-specific but the differential expression in malignant tumors is also the focus of claudin-related research. In addition to up- or down-regulation, claudin proteins also undergo delocalization, which plays a vital role in tumor invasion and aggressiveness. Claudin (CLDN)-1 is the most-studied claudin in cancers and to date, its role as either a tumor promoter or suppressor (or both) is not established. In some cancers, lower expression of CLDN-1 is shown to be associated with cancer progression and invasion, while in others, loss of CLDN-1 improves the patient survival. Another topic of discussion regarding the significance of CLDN-1 is its localization (nuclear or cytoplasmic vs perijunctional) in diseased states. This article reviews the evidence regarding CLDN-1 in cancers either as a tumor promoter or suppressor from the literature and we also review the literature regarding the pattern of CLDN-1 distribution in different cancers, focusing on whether this localization is associated with tumor aggressiveness. Furthermore, we utilized expression data from The Cancer Genome Atlas (TCGA) to investigate the association between CLDN-1 expression and overall survival (OS) in different cancer types. We also used TCGA data to compare CLDN-1 expression in normal and tumor tissues. Additionally, a pathway interaction analysis was performed to investigate the interaction of CLDN-1 with other proteins and as a future therapeutic target.

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Section: Claudin-1 and Ovarian Cancermentioning

confidence: 99%

“…Recently, the level of CLDN-1 expression was also investigated in borderline tumors of the ovary (BOT) [53]. A significantly higher level of CLDN-1 expression was associated with the peritoneal implants and micropapillary patterns that are specifically seen only in serous BOT [53].…”

Section: Claudin-1 and Ovarian Cancermentioning

confidence: 99%

Claudin-1, A Double-Edged Sword in Cancer

Bhat

Syed

Therachiyil

et al. 2020

IJMS

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“…62 In addition, El-Balat et al found that Claudin-1 is related to predictors of poor prognosis (eg, peritoneal implantation and micropapillary pattern), and the authors hypothesized that the overexpression of Claudin-1 may be related to the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. 63 Different from inhibited p53 signaling in high-grade serous ovarian cancer (HGSOC), overexpressed p53 and changes in genes associated with the p53 pathway were observed in SBOTs. 64 Cheng et al 65 confirmed that SBOTs contained wild-type p53 by sequencing.…”

Section: Gene Expression and Pathways Alteration In Botsmentioning

confidence: 99%

<p>The Diagnosis, Treatment, Prognosis and Molecular Pathology of Borderline Ovarian Tumors: Current Status and Perspectives</p>

Sun¹,

Xu²,

Jia³

2020

CMAR

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Borderline ovarian tumors (BOTs) are a type of low malignant potential tumor that is typically associated with better outcomes than ovarian cancer. Indeed, its 10-year survival rate is as high as 95%. However, there is a small subset of patients who experience relapse and eventually die. It has been shown that the prognosis of BOTs was based on pathological diagnosis, the age at diagnosis, pre-operative carbohydrate antigen 125 level, invasive implants, and micropapillary patterns. Now the molecular-targeted therapy and molecular-genetic diagnosis have developed into a form of precision medicine. Recent studies on extensive molecular characterizations and molecular pathological mechanisms of BOTs have helped us understand the genomic landscapes of BOTs, and therefore BOTs could be reclassified into biologically and clinically more accurate and effective subtypes. The purpose of this review is to summarize current status for the diagnosis and treatment of BOTs and to describe the research progress on molecular pathologies, with a goal of providing a theoretical perspective for the diagnosis and treatment of BOTs.

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“…Recent studies have inferred several assumptions, including the incessant ovulation, gonadotropin, hormonal, and inflammation hypotheses, to explain the tumorigenesis of serous BOTs [ 17 , 18 , 19 ]. Serous BOTs are characterized by mutations in the KRAS , BRAF , and ERBB2 genes and overexpression of the p53 and Claudin-1 genes; furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, PI3K/AKT/mTOR pathway, Hedgehog pathway, and angiogenesis pathway are frequently activated in serous BOTs [ 13 , 14 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic AHR Binding Pathway with EMT Effects on Serous Ovarian Tumors Recognized by Multidisciplinary Integrated Analysis

Gao

Chang

et al. 2021

Biomedicines

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Epithelial ovarian cancers (EOCs) are fatal and obstinate among gynecological malignancies in advanced stage or relapsed status, with serous carcinomas accounting for the vast majority. Unlike EOCs, borderline ovarian tumors (BOTs), including serous BOTs, maintain a semimalignant appearance. Using gene ontology (GO)-based integrative analysis, we analyzed gene set databases of serous BOTs and serous ovarian carcinomas for dysregulated GO terms and pathways and identified multiple differentially expressed genes (DEGs) in various aspects. The SRC (SRC proto-oncogene, non-receptor tyrosine kinase) gene and dysfunctional aryl hydrocarbon receptor (AHR) binding pathway consistently influenced progression-free survival and overall survival, and immunohistochemical staining revealed elevated expression of related biomarkers (SRC, ARNT, and TBP) in serous BOT and ovarian carcinoma samples. Epithelial–mesenchymal transition (EMT) is important during tumorigenesis, and we confirmed the SNAI2 (Snail family transcriptional repressor 2, SLUG) gene showing significantly high performance by immunohistochemistry. During serous ovarian tumor formation, activated AHR in the cytoplasm could cooperate with SRC, enter cell nuclei, bind to AHR nuclear translocator (ARNT) together with TATA-Box Binding Protein (TBP), and act on DNA to initiate AHR-responsive genes to cause tumor or cancer initiation. Additionally, SNAI2 in the tumor microenvironment can facilitate EMT accompanied by tumorigenesis. Although it has not been possible to classify serous BOTs and serous ovarian carcinomas as the same EOC subtype, the key determinants of relevant DEGs (SRC, ARNT, TBP, and SNAI2) found here had a crucial role in the pathogenetic mechanism of both tumor types, implying gradual evolutionary tendencies from serous BOTs to ovarian carcinomas. In the future, targeted therapy could focus on these revealed targets together with precise detection to improve therapeutic effects and patient survival rates.

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Claudin-1 is linked to presence of implants and micropapillary pattern in serous borderline epithelial tumours of the ovary

Cited by 6 publications

References 37 publications

Claudin-1, A Double-Edged Sword in Cancer

Claudin-1, A Double-Edged Sword in Cancer

<p>The Diagnosis, Treatment, Prognosis and Molecular Pathology of Borderline Ovarian Tumors: Current Status and Perspectives</p>

Synergistic AHR Binding Pathway with EMT Effects on Serous Ovarian Tumors Recognized by Multidisciplinary Integrated Analysis

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