The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling

AbstractOvarian cancer is characterized by dysbiosis, referred to as oncobiosis in neoplastic diseases. In ovarian cancer, oncobiosis was identified in numerous compartments, including the tumor tissue itself, the upper and lower female genital tract, serum, peritoneum, and the intestines. Colonization was linked to Gram-negative bacteria with high inflammatory potential. Local inflammation probably participates in the initiation and continuation of carcinogenesis. Furthermore, local bacterial colonies in the peritoneum may facilitate metastasis formation in ovarian cancer. Vaginal infections (e.g. Neisseria gonorrhoeae or Chlamydia trachomatis) increase the risk of developing ovarian cancer. Bacterial metabolites, produced by the healthy eubiome or the oncobiome, may exert autocrine, paracrine, and hormone-like effects, as was evidenced in breast cancer or pancreas adenocarcinoma. We discuss the possible involvement of lipopolysaccharides, lysophosphatides and tryptophan metabolites, as well as, short-chain fatty acids, secondary bile acids and polyamines in the carcinogenesis of ovarian cancer. We discuss the applicability of nutrients, antibiotics, and probiotics to harness the microbiome and support ovarian cancer therapy. The oncobiome and the most likely bacterial metabolites play vital roles in mediating the effectiveness of chemotherapy. Finally, we discuss the potential of oncobiotic changes as biomarkers for the diagnosis of ovarian cancer and microbial metabolites as possible adjuvant agents in therapy.

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Serous Ovarian Cancer Signaling Pathways

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000079 ◽

2014 ◽

Vol 24 (3) ◽

pp. 410-417 ◽

Cited By ~ 7

Author(s):

Ioannis C. Kotsopoulos ◽

Alexios Papanikolaou ◽

Alexandros F. Lambropoulos ◽

Konstantinos T. Papazisis ◽

Dimitrios Tsolakidis ◽

...

Keyword(s):

Ovarian Cancer ◽

Signaling Pathways ◽

Current Knowledge ◽

Female Genital Tract ◽

Serous Ovarian Cancer ◽

Cellular Processes ◽

Novel Biomarkers ◽

Precise Role ◽

Female Genital

AbstractOvarian cancer is the most lethal malignancy of the female genital tract, mainly due to the failure of early diagnosis and the limitations posed by the conventional chemotherapies. Current research has focused in the study of cascades of various cellular molecular reactions, known as signaling pathways. In this review article, authors try to describe the current knowledge regarding the signaling pathways that influence multiple cellular processes in serous ovarian cancer and especially the pathogenesis. Thorough understanding of the precise role of these pathways can lead to the development of new and more effective targeted therapies as well as novel biomarkers in ovarian cancer.

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lncRNA SNHG15 Promotes Ovarian Cancer Progression through Regulated CDK6 via Sponging miR-370-3p

BioMed Research International ◽

10.1155/2021/9394563 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yi Wang ◽

Minghong Ding ◽

Xiaoqing Yuan ◽

Ruibao Jiao ◽

Dagao Zhu ◽

...

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanism ◽

Cancer Progression ◽

Female Genital Tract ◽

Vital Role ◽

Cancer Proliferation ◽

Promising Target ◽

Tumor Tissues ◽

Female Genital

Ovarian cancer is a kind of cancer from the female genital tract; the molecular mechanism still needs to be explored. lncRNA plays a vital role in tumorigenesis and development. Our aim was to identify oncogenic lncRNAs in ovarian cancer and explore the potential molecular mechanism. SNHG15 was initially identified by using GEO datasets (GSE135886 and GSE119054) and validated by tumor tissues and the cell line, identifying that SNHG15 was upregulated in ovarian cancer. Besides, high SNHG15 indicated poor prognosis in ovarian cancer. Furthermore, knockdown SNHG15 suppresses ovarian cancer proliferation and promotes apoptosis. Mechanistically, SNHG15 promotes proliferation through upregulated CDK6 via sponging miR-370-3p. Taken together, our findings emphasize the important role of SNHG15 in ovarian cancer, suggesting that SNHG15 may be a promising target for ovarian cancer.

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Molecular Biology of Ovarian Cancer: From Mechanisms of Intraperitoneal Metastasis to Therapeutic Opportunities

Cancers ◽

10.3390/cancers13071661 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1661

Author(s):

Krzysztof Książek

Keyword(s):

Ovarian Cancer ◽

Molecular Biology ◽

Cause Of Death ◽

Genital Tract ◽

Female Genital Tract ◽

Gynecological Tumors ◽

Female Genital

Ovarian cancer (OC) is one of the most frequent malignancies of the female genital tract, and is still the leading cause of death from gynecological tumors [...]

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Evidence for cGAS-STING signaling in the female genital tract resistance to Chlamydia trachomatis infection

Infection and Immunity ◽

10.1128/iai.00670-21 ◽

2022 ◽

Author(s):

Xin Su ◽

Hong Xu ◽

Maegan French ◽

Yujie Zhao ◽

Lingli Tang ◽

...

Keyword(s):

Innate Immunity ◽

Chlamydia Trachomatis ◽

Signaling Pathway ◽

Genital Tract ◽

Essential Role ◽

Cultured Cells ◽

Female Genital Tract ◽

Lower Genital Tract ◽

Female Genital

Sexually transmitted Chlamydia trachomatis can ascend to the upper genital tract due to its resistance to innate immunity in the lower genital tract. C. trachomatis can activate cGAS-STING signaling pathway in cultured cells via either cGAS or STING. The current study was designed to evaluate the role of the cGAS-STING pathway in innate immunity against C. trachomatis in the mouse genital tract. Following intravaginal inoculation, C. trachomatis significantly declined by day 5 following a peak infection on day 3 while the mouse-adapted C. muridarum continued to rise for >1 week, indicating that C. trachomatis is susceptible to the innate immunity in the female mouse genital tract. This conclusion was supported by the observation of a similar shedding course in mice deficient in adaptive immunity. Thus, C. trachomatis can be used to evaluate innate immunity in the female genital tract. It was found that mice deficient in either cGAS or STING significantly increased the yields of live C. trachomatis on day 5, indicating an essential role of the cGAS-STING signaling pathway in innate immunity of the mouse genital tract. Comparison of live C. trachomatis recovered from different genital tissues revealed that the cGAS-STING-dependent immunity against C. trachomatis was restricted to the mouse lower genital tract regardless of whether C. trachomatis was inoculated intravaginally or transcervically. Thus, we have demonstrated an essential role of the cGAS-STING signaling pathway in innate immunity against chlamydial infection, laying a foundation for further illuminating the mechanisms of the innate immunity in the female lower genital tract.

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The role of polymorphisms occurring in BRCA1/2 genes in determining ovarian cancer risk.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17551 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17551-e17551

Author(s):

Marta Castiglia ◽

Lorena Incorvaia ◽

Alessandro Perez ◽

Chiara Brando ◽

Antonio Galvano ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Risk ◽

Small Sample Size ◽

Female Genital Tract ◽

Brca1 Gene ◽

Small Sample ◽

Clinicopathological Features ◽

Age At Diagnosis ◽

Ovarian Cancer Risk

e17551 Background: Ovarian cancer (OC) is the 10th tumor occurring in women, it accounts for 30% of all malignant tumor affecting female genital tract in Italy. There are several factors that contribute to OC development; in 15-25% of cases family history of breast and ovarian cancer represent the main risk factor. It is well known that pathogenic variants (PVs) occurring in BRCA1/2 genes strongly increase the risk of developing OC, ranging from 50% in BRCA1 PVs carriers to 30% in BRCA2 PVs carriers. Recently genetic polymorphism has been shown to increase cancer risk, consequently polymorphisms in BRCA1/2 genes could represent low penetrance susceptibility alleles and contribute to determine specific clinicopathological features in OC patients harboring BRCA1/2 PVs. Methods: From 2015 to 2021, 338 patients diagnosed with epithelial OC (not mucinous, not borderline) were subjected to BRCA1/2 analysis. After obtaining informed consent, blood samples were processed for genomic DNA isolation; DNA was used for library preparation with the BRaCa Screen kit. Sequencing was performed on the IonS5 platform; variant annotation was performed with Amplicon Suite software. We collected data of both PVs and polymorphisms in BRCA1/2 genes with the aim to evaluate whether a cluster of specific polymorphisms could impact clinicopathological features in BRCA1 PVs carriers. Results: Among the 338 screened EOC, BRCA1/2 PVs were reported in 85 patients (25%). 66% of patients harbored BRCA1 PVs and 34% in BRCA2. The most frequent BRCA1 PVs were the c.4964_4982del (5083del19), c.514delC and c.181T > G; the first and the last are known for their founder effect in Italy and Eastern Europe. Looking at BRCA1 gene, in 75% of patients we identified a polymorphisms cluster (c.2082C > T, c.2311T > C, c.2612C > T, c.3113A > G, c.3548A > G, c.4308T > C, c.4837A > G). The c.514delC and c.181T > G PVs are always associated with the cluster and two additional polymorphisms, the c.2077G > A and the c.1067A > G respectively. Conversely, the cluster seems not to be associated with the PVs 5083del19. Interestingly in BRCA1-5083del19 PV carriers median age at OC diagnosis was 50 years (range 45-69). On average, these patients developed ovarian cancer 6 years earlier than other BRCA1 PV carriers (median age at diagnosis 57 years; range 30-81). Bilateral tumors were frequent and occurred in 57% of the patients versus 33% in OC patients carrying other BRCA1 PVs. Therefore, it seems that the cluster has a “protective” effect and that its absence reduces age at diagnosis. Conclusions: Despite this study has the main limitation of a small sample size, we have reported a possible association between polymorphisms cluster and clinicopathological features in BRCA1 PVs carriers. By further investigating this aspect in a larger cohort, we might be able to prove the role of this cluster in increasing or reducing OC risk and providing clinicians more information useful for patients’ stratification.

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Surgical Prevention in Ovarian Cancer

Handbook of Research on Oncological and Endoscopical Dilemmas in Modern Gynecological Clinical Practice - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-7998-4213-2.ch014 ◽

2021 ◽

pp. 194-206

Author(s):

Alexios Papanikolaou ◽

Anastasios Liberis ◽

Anastasia Vatopoulou

Keyword(s):

Ovarian Cancer ◽

Primary Prevention ◽

Early Detection ◽

Early Diagnosis ◽

Genital Tract ◽

Female Genital Tract ◽

Current Evidence ◽

Advanced Stage ◽

Stage Disease

Ovarian cancer is the second most common malignant disease of the female genital tract, but the first in mortality because it is usually diagnosed at an advanced stage. Options for early detection, diagnosis, and treatment are limited. Prevention of ovarian cancer relates to primary prevention by avoiding factors that are epidemiologically associated with an increased incidence of ovarian cancer and the adoption of protective habits. These include interventions to exclude the fallopian tubes and ovaries. Secondary prevention is related to early diagnosis. The chapter aims to summarize current evidence on prevention of ovarian cancer as well as role of surgery to prevent advanced-stage disease.

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