Chronic inflammation in endometriosis and endometriosis-associated ovarian cancer: New roles for the “old” complement pathway

Edwards, Robert P.; Huang, Xin; Vlad, Anda

doi:10.1080/2162402x.2014.1002732

Cited by 30 publications

(19 citation statements)

References 10 publications

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“…The immune microenvironment is critical for the carcinogenesis of EAOC. The cell proliferation resulted from aberrations humoral immunity and complement pathway activation was postulated to play a major role in the pathogenesis of EAOC [ 22 ]. Cancer-immune phenotypes in humans can be divided into three main categories: the immune-desert phenotype, the immune–excluded phenotype and the inflamed phenotype.…”

Section: Discussionmentioning

confidence: 99%

Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma

Chang

Wang

et al. 2017

Oncotarget

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The coexistence of endometriosis (ES) with ovarian clear cell carcinoma (CCC) or endometrioid carcinoma (EC) suggested that malignant transformation of ES leads to endometriosis associated ovarian carcinoma (EAOC). However, there is still lack of an integrating data analysis of the accumulated experimental data to provide the evidence supporting the hypothesis of EAOC transformation. Herein we used a function-based analytic model with the publicly available microarray datasets to investigate the expression profiling between ES, CCC, and EC. We analyzed the functional regularity pattern of the three type of samples and hierarchically clustered the gene sets to identify key mechanisms regulating the malignant transformation of EAOC. We identified a list of 18 genes (NLRP3, AIM2, PYCARD, NAIP, Caspase-4, Caspase-7, Caspase-8, TLR1, TLR7, TOLLIP, NFKBIA, TNF, TNFAIP3, INFGR2, P2RX7, IL-1B, IL1RL1, IL-18) closely related to inflammasome complex, indicating an important role of inflammation/immunity in EAOC transformation. We next explore the association between these target genes and patient survival using Gene Expression Omnibus (GEO), and found significant correlation between the expression levels of the target genes and the progression-free survival. Interestingly, high expression levels of AIM2 and NLRP3, initiating proteins of inflammasomes, were significantly correlated with poor progression-free survival. Immunohistochemistry staining confirmed a correlation between high AIM2 and high Ki-67 in clinical EAOC samples, supporting its role in disease progression. Collectively, we established a bioinformatic platform of gene-set integrative molecular functionome to dissect the pathogenic pathways of EAOC, and demonstrated a key role of dysregulated inflammasome in modulating the malignant transformation of EAOC.

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Section: Discussionmentioning

confidence: 99%

Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma

Chang

Wang

et al. 2017

Oncotarget

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“…The complement pathway has been linked with supporting tumour growth through various mechanisms [ 113 ]. In 2015, Edwards et al demonstrated that 85% of atypical endometriosis lesions demonstrated a cancer-like immunological gene signature, compared to 30% of typical endometriosis lesions [ 114 ]. In 2015, a meta-analysis reported by Lee et al including over 15,000 ovarian cancer patients, evaluated the 38 putative endometriosis-associated SNPs identified by Nyholt in 2012 [ 12 ].…”

Section: Development Of Eaoc From Endometriosismentioning

confidence: 99%

Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development

Dawson¹,

Fernández²,

Anglesio³

et al. 2018

ecancer

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Endometriosis is a fascinating disease that we strive to better understand. Molecular techniques are shedding new light on many important aspects of this disease: from pathogenesis to the recognition of distinct disease variants like deep infiltrating endometriosis. The observation that endometriosis is a cancer precursor has now been strengthened with the knowledge that mutations that are present in endometriosis-associated cancers can be found in adjacent endometriosis lesions. Recent genomic studies, placed in context, suggest that deep infiltrating endometriosis may represent a benign neoplasm that invades locally but rarely metastasises. Further research will help elucidate distinct aberrations which result in this phenotype. With respect to identifying those patients who may be at risk of developing endometriosis-associated cancers, a combination of molecular, pathological, and inheritance markers may define a high-risk group that might benefit from risk-reducing strategies.

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“…Atypical endometriosis is the intermediate stage in the process of transformation of endometriosis into cancer. On histology, it is characterized by hypercellularity, enlarged nuclei, as well as by pleomorphism [4].…”

mentioning

confidence: 99%

Seromucinous ovarian tumors and endometriosis in reproductive-aged wo

Shamarakova¹,

Adamyan²,

Asaturova³

et al. 2018

Akusherstvo i ginekologiia

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Endometriosis affects up to 15% of reproductive-aged women. Consideration of this nosological entity in a new aspect is impelled by the evidence that 0.5-1% of cases are complicated by endometriosis-associated ovarian neoplasms represented mainly by the endometrioid and clear-cell subtypes of tumors. This category also includes seromucinous ovarian tumors (SMOTs). Objective. To investigate the morphological and immunohistochemical (IHC) features of SMOTs in reproductiveaged women, including pregnant ones. Subjects and methods. Ovarian tumor samples from 15 patients who had been operated on in 2012-2016 were analyzed comprehensively at the National Medical Research Center of Obstetrics, Gynecology, and Perinatology: IHC examination was conducted using the biomarkers of estrogen and progesterone receptors and Ki-67. Results. Borderline SMOTs were characterized by papillary growths on the inner surface (in one case) and on the outer surface, with an adhesive process with the serous surface of the corpus uteri (FIGO Stage 1c), and mixed epithelial structures; leukocyte infiltration was observed in four cases. The epithelium of seromucinous carcinoma (n = 1) was similar to that of serous, endocervical, and endometrial types at the same time. All the samples exhibited low Ki-67 expression and high positive receptor immunoreactivity. Endometriosis diagnosed in nine women was accompanied by benign seromucinous cystadenomas (n = 4), borderline tumors (n = 4), and carcinoma (n = 1). Conclusion. Most of the examined SMOTs showed the areas, covered with the endometrioid epithelium, with adjacent endometrial stroma, which indicated the development of carcinoma in the presence of endometrioid cyst. The revealed facts suggest that endometriosis plays an etiological role in developing SMOTs. When detected, most neoplasms are localized (limited to ovarian tissue, FIGO stage 1a) and characterized by a favorable prognosis as a whole.

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Chronic inflammation in endometriosis and endometriosis-associated ovarian cancer: New roles for the “old” complement pathway

Cited by 30 publications

References 10 publications

Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma

Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma

Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development

Seromucinous ovarian tumors and endometriosis in reproductive-aged wo

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