Genetic variation in progesterone receptor gene and ovarian cancer risk: A case control study

Kanabekova, Perizat; Al-Awadi, Amina; Bauyrzhanova, Zhansaya; Tahtouh, Tania; Sarray, Sameh; Almawi, Wassim Y.

doi:10.1016/j.gene.2022.146288

Cited by 5 publications

(1 citation statement)

References 35 publications

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“…Conversely, low levels of PGR expression are characteristic of aggressive forms of the disease and are linked to poorer outcomes. Additionally, certain polymorphisms in the hormone-binding domain of the PGR gene have been associated with an increased risk of ovarian cancer [47][48][49]. Progesterone's protective effect may be attributed to PGR's suppression of progesterone receptor membrane component-1 (PGRMC1), which increases the sensitivity of ovarian cancer cells to platinum-based chemotherapy [19].…”

Section: Discussionmentioning

confidence: 99%

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

Timofeeva

Fedorov

Asaturova

et al. 2023

IJMS

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The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial–mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment’s effectiveness and the patient’s longevity.

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Section: Discussionmentioning

confidence: 99%

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

Timofeeva

Fedorov

Asaturova

et al. 2023

IJMS

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Decreased risk of ovarian cancer associated with rs9898876 sex hormone-binding globulin gene variant

et al. 2022

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Background. Ovarian cancer (OC) is one of the most common gynecologic cancers,with signi cant morbidity and mortality. The risk of OCis in uenced by hormone status, of which sex hormone-binding globulin (SHBG), whichin uences the serum availability of steroid sex hormones, is implicated in the pathogenesis and evolution of OC. The aim of this study is to evaluate the involvement of common SHBG gene variants in OC susceptibility and evolution.Materials. A case control study including 71 OC patients and 74 cancer-free controls, who were genotyped for rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP. Genotyping was done by the allelic discrimination method, using VIC-and FAM-labeled primers.Results. The minor allele frequencies of rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP was comparable between OC cases and control women, implying no signi cant associations of the tested variants and overall OC risk. Taking homozygous wild-type genotype as reference (OR=1.00), heterozygous rs9898876 (G/T), and minor allele-carrying genotypes [G/T+T/T] were associated with reduced risk of OC. Whilers9898876 heterozygosity (G/T) was predictive of OC occurrence, no signi cant association of the remaining three tested SNPs was noted with altered risk of OC. Irrespective of FIGO staging, the four tested SHBG SNPs were not associated with the clinical progression of OC. Conclusion.In conclusion, SHBG rs9898876 is associated with a decreased risk of OC, and thus constitutes a potential diagnostic biomarker of OC.

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Low androgen/progesterone or high oestrogen/androgen receptors ratio in serous ovarian cancer predicts longer survival

Gogola-Mruk,

Pietrus,

Piechowicz

et al. 2024

Reproductive Biology

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Genetic variation in progesterone receptor gene and ovarian cancer risk: A case control study

Cited by 5 publications

References 35 publications

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

Decreased risk of ovarian cancer associated with rs9898876 sex hormone-binding globulin gene variant

Low androgen/progesterone or high oestrogen/androgen receptors ratio in serous ovarian cancer predicts longer survival

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