The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer

Liu, Chao Lien; Yuan, Ray-Hwang; Mao, Tsui Lien

doi:10.3390/biom11070998

Cited by 6 publications

(3 citation statements)

References 133 publications

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“…The study demonstrated that next-generation sequencing in biopsy specimens from patients with relapsed-refractory cancer enables the qualification of nearly 20% of patients to evidence-based investigational therapy. However, co-occurring resistance mutations were common and that fact needs investigation of drug combination therapy regimens [101]. Another example of individualized therapy was a prospective MOSCATO 01 clinical trial.…”

Section: Personalization Of Treatment-state Of Art and Future Directionsmentioning

confidence: 99%

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

Wilczyński,

Paradowska,

Wilczyński

2023

JPM

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High-grade serous tubo-ovarian cancer (HGSTOC) is the most lethal tumor of the female genital tract. The foregoing therapy consists of cytoreduction followed by standard platinum/taxane chemotherapy; alternatively, for primary unresectable tumors, neo-adjuvant platinum/taxane chemotherapy followed by delayed interval cytoreduction. In patients with suboptimal surgery or advanced disease, different forms of targeted therapy have been accepted or tested in clinical trials. Studies on HGSTOC discovered its genetic and proteomic heterogeneity, epigenetic regulation, and the role of the tumor microenvironment. These findings turned attention to the fact that there are several distinct primary tumor subtypes of HGSTOC and the unique biology of primary, metastatic, and recurrent tumors may result in a differential drug response. This results in both chemo-refractoriness of some primary tumors and, what is significantly more frequent and destructive, secondary chemo-resistance of metastatic and recurrent HGSTOC tumors. Treatment possibilities for platinum-resistant disease include several chemotherapeutics with moderate activity and different targeted drugs with difficult tolerable effects. Therefore, the question appears as to why different subtypes of ovarian cancer are predominantly treated based on the same therapeutic schemes and not in an individualized way, adjusted to the biology of a specific tumor subtype and temporal moment of the disease. The paper reviews the genomic, mutational, and epigenetic signatures of HGSTOC subtypes and the tumor microenvironment. The clinical trials on personalized therapy and the overall results of a new, comprehensive approach to personalized therapy for ovarian cancer have been presented and discussed.

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Section: Personalization Of Treatment-state Of Art and Future Directionsmentioning

confidence: 99%

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

Wilczyński,

Paradowska,

Wilczyński

2023

JPM

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“…The majority of ovarian cancer cases are of epithelial origin; epithelial ovarian cancer. About 75% of these cases are diagnosed at stages IIIc and IV where the 5-year survival rate is less than 30% [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

PCDH17 gene promoter methylation status in a cohort of Egyptian women with epithelial ovarian cancer

et al. 2023

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Background and objective Ovarian cancer is a leading cause of female mortality. Epigenetic changes occur in early stages of carcinogenesis and represent a marker for cancer diagnosis. Protocadherin 17 (PCDH17) is a tumor suppressor gene involved in cell adhesion and apoptosis. The methylation of PCDH17 gene promoter has been described in several cancers including ovarian cancer. The aim of the study was to compare the methylation status of PCDH17 gene promoter between females diagnosed with epithelial ovarian cancer and a control group composed of normal and benign ovarian lesions. Methods Fifty female subjects were included in our study (25 ovarian cancer patients and 25 controls). DNA was extracted from Formalin-Fixed Paraffin-Embedded (FFPE) tissues of the subjects. Methylation levels for six CpG sites in the PCDH17 gene promoter were assessed by pyrosequencing. Results The methylation levels at five out of six sites were significantly higher in females with epithelial ovarian cancer compared to the control group. Moreover, the same applies for the mean methylation level with p value 0.018. Conclusion Methylation of PCDH17 gene promoter plays a role in ovarian carcinogenesis and can be used for diagnosis and early detection.

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“…Over 90% of OC cases originate from the epithelium, which is known as epithelial ovarian cancer (EOC) [6]. EOC is typically asymptomatic in its early stage, and over 75% of EOCs cases are found at an advanced stage when the tumor metastasizes to the perineum, which is classified as stage IIIC and IV cancer by the International Federation of Gynecology and Obstetrics (FIGO) [7]. This substantially increases mortality since the 5-year survival rate drops when cancer metastasizes to the pelvic cavity.…”

Section: Introductionmentioning

confidence: 99%

TIPE2 acts as a tumor suppressor and correlates with tumor microenvironment immunity in epithelial ovarian cancer

Gao

Qiu

et al. 2023

Aging

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Background: Epithelial ovarian cancer (EOC) is one of the deadliest gynecologic cancers. The etiology of EOC has still not been elucidated thoroughly. Tumor necrosis factor-α-induced protein 8-like2 (TNFAIP8L2, TIPE2), an important regulator of inflammation and immune homeostasis, plays a critical role in the progression of various cancers. This study aims to investigate the role of TIPE2 in EOC. Methods: Expression of TIPE2 protein and mRNA in EOC tissues and cell lines was examined using Western blot and quantitative real-time PCR (qRT-PCR). The functions of TIPE2 in EOC were investigated by cell proliferation assay, colony assay, transwell assay, and apoptosis analysis in vitro. To further investigate the regulatory mechanisms of TIPE2 in EOC, RNA-seq and western blot were performed. Finally, the CIBERSORT algorithm and databases including Tumor Immune Single-cell Hub (TISCH), Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction (TISIDB), and The Gene Expression Profiling Interactive Analysis (GEPIA) were used to elucidate its potential role in regulating tumor immune infiltration in the tumor microenvironment (TME). Results: TIPE2 expression was shown to be considerably lower in both EOC samples and cell lines. Overexpression of TIPE2 suppressed EOC cell proliferation, colony formation, and motility in vitro. Mechanistically, TIPE2 suppressed EOC by blocking the PI3K/Akt signaling pathway, according to bioinformatics analysis and western blot in TIPE2 overexpression EOC cell lines, and the anti-oncogenic potentials of TIPE2 in EOC cells could be partially abrogated by the PI3K agonist, 740Y-P. Finally, TIPE2 expression was positively associated with various immune cells and possibly involved in the regulation of macrophage polarization in ovarian cancer. Conclusions: We detail the regulatory mechanism of TIPE2 in EOC carcinogenesis, as well as how it correlates with immune infiltration, emphasizing its potential as a therapeutic target in ovarian cancer.

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The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer

Cited by 6 publications

References 133 publications

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

PCDH17 gene promoter methylation status in a cohort of Egyptian women with epithelial ovarian cancer

TIPE2 acts as a tumor suppressor and correlates with tumor microenvironment immunity in epithelial ovarian cancer

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