Biologic Mechanisms Linked to Prognosis in Ovarian Cancer that May Be Affected by Aging.
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ABSTRACT:
SUBMITTER: Chon HS
PROVIDER: S-EPMC6584919 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This is a short review of the basic molecular mechanisms of ovarian aging, written with a particular focus on the use of this data to improve the diagnostic and therapeutic protocols both for women affected by physiological (age-related) ovarian decay and for those suffering premature ovarian insufficiency. Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes. The correct diagnosis of the molecular mechanisms involved in ovarian aging can serve to design treatment strategies that can slow down ovarian decay and increase the quantity and quality of oocytes that can be obtained for an in vitro fertilization attempt. The available treatment options include the use of antioxidants, melatonin, growth hormones, and mitochondrial therapies. All of these treatments have to be considered in the context of each couple's history and current clinical condition, and a customized (patient-tailored) treatment protocol is to be elaborated.
| S-EPMC7866420 | biostudies-literature
Project description:As peripheral blood contains fluctuated levels of circulating cell-free mitochondrial DNA (ccf mtDNA), we aimed to evaluate ccf mtDNA as a biomarker for diagnosis and prognosis of epithelial ovarian cancer (EOC). In the present study, we recruited 165 EOC patients and 60 healthy women. Quantitative RT-PCR was applied to amplify 79-bp and 230-bp fragments of the mitochondrial 16 s RNA gene in sera of these participants. MtDNA integrity was defined as the ratio of long to short mtDNA fragments. We observed that the levels of mtDNA79 and mtDNA230 were significantly increased (P?=?.0001), whereas the mtDNA integrity (P?=?.0001) was decreased in EOC patients compared with those in healthy controls. MtDNA79 showed a sensitivity of 90.3% and a specificity of 81.7% (AUC?=?0.900) to discriminate EOC from healthy controls. Moreover, the amounts of mtDNA79 (P?=?.0001, P?=?.012, P?=?.039) and mtDNA230 (P?=?.0001, P?=?.042) continuously raised from healthy controls over FIGO I-II to FIGO III and IV, with highest levels of mtDNA79 (P?=?.0001) and mtDNA230 (P?=?.0001) in FIGO III and IV. Increasing levels of mtDNA79 (P?=?.003, P?=?.0001) and mtDNA230 (P?=?.041, P?=?.0001) were also associated with lymph node metastasis and CA125 values. The higher levels of mtDNA79 (P?=?.0001; HR 3.2, 95%CI:1.6-6.3) and mtDNA230 (borderline P?=?.048, HR 0.9, 95%CI:0.9-1.0) also correlated with poor patients' overall survival, of which mtDNA79 could act as an independent factor for overall survival. Our data show a significant association of increasing levels of ccf mtDNA with EOC progress and poor prognosis.
| S-EPMC6609736 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-06-03 | GSE240693 | GEO
Project description:BackgroundOne of the most usual gynecological state of tumor is ovarian cancer and is a major reason of gynecological tumor-related global mortality rate. There have been multiple risk elements related to ovarian cancer like the background of past cases associated with breast cancer or ovarian cancer, or excessive body weight issues, case history of smoking, and untimely menstruation or menopause. Because of unclear expressions, more than 70% of the ovarian cancer patient cases are determined during the early stage. Material and Methods. GSE38666, GSE40595, and GSE66957 were the three microarray datasets which were analyzed using GEO2R for screening the differentially expressed genes. GO, Kyoto Encyclopedia of Genes, and protein expression studies were performed for analysis of hub genes. Then, survival analysis was performed for all the hub genes.ResultsFrom the dataset, a total of 199 differentially expressed genes (DEGs) were identified. Through the KEGG pathway study, it was noted that the DEGs are mainly linked with the AGE-RAGE signaling pathway, central carbon metabolism, and human papillomavirus infection. The survival analysis showed 4 highly expressed hub genes COL4A1, SDC1, CDKN2A, and TOP2A which correlated with overall survival in ovarian cancer patients. Moreover, the expression of the 4 hub genes was validated by the GEPIA database and the Human Protein Atlas.ConclusionThe results have shown that all 4 hub genes were found to be upregulated in ovarian cancer tissues which predict poor prognosis in patients with ovarian cancer.
| S-EPMC8763496 | biostudies-literature
Project description:The aim of the present study was to evaluate the expression of the chemokine ligand 18 (CCL18) gene in ovarian cancer and to investigate the effects of its overexpression or suppression on growth, invasion, and metastasis in an ovarian carcinoma cell line (SKOV3) in vitro. CCL18 mRNA expression in epithelial ovarian carcinoma (EOC), benign ovarian tumor and normal ovarian tissues was measured by fluorescence quantitative polymerase chain reaction. A CCL18 restructuring plasmid was constructed, and SKOV3 cells were transfected with the plasmid DNA in vitro. A restructuring interference vector was also transfected into CCL18-positive SKOV3 cells. The growth curves, cell cycle distribution, and invasive, migrative and adhesive capacities of SKOV3 cells following overexpression and suppression of CCL18 were evaluated by MTT assay, flow cytometry, Transwell assay, migration assay, and the fibronectin adhesion method, respectively. The positive expression rate of CCL18 in EOC was significantly higher than in benign ovarian tumor (P = 0.002) and normal ovarian tissues (P = 0.003). However, there was no statistical significance in the expression of CCL18 with regard to clinical pathology (including histological classification, pathological grade and surgical pathological stage), and the median survival times of CCL18-positive and CCL18-negative patients did not differ significantly. The invasive, migrative, and adhesive capacities of SKOV3-CCL18 cells were significantly higher than those of SKOV3 and SKOV3-vector cells (P < 0.05). However, there was no significant difference in cell proliferation between the SKOV3-CCL18 and negative control cells. The invasive, migrative, and adhesive capacities of the pSilencer4.1-CCL18-small interfering RNA127 group were significantly lower than those of non-transfected pSilencer4.1-negative and pSilencer4.1 groups (P < 0.05). In conclusion, the overexpression and silencing of CCL18 affected invasion, adhesion, and migration in EOC cells; thus CCL18 may have potential as a clinical marker for early diagnosis of malignant ovarian tumors, and as a target molecule in the treatment of ovarian cancer.
| S-EPMC6949555 | biostudies-literature
Project description:Tissue specificity is a fundamental property of an organ that affects numerous biological processes, including aging and longevity, and is regulated by the circadian clock. However, the distinction between circadian-affected tissue specificity and other tissue specificities remains poorly understood. Here, using multi-omics data on circadian rhythms in mice, we discovered that approximately 35% of tissue-specific genes are directly affected by circadian regulation. These circadian-affected tissue-specific genes have higher expression levels and are associated with metabolism and hepatocyte cells. They also exhibit specific features in long-reads sequencing data. Notably, these genes are associated with aging and longevity at both the gene level and at the network module level. The expression of these genes oscillates in response to caloric and time-restricted feeding regimens, which have been demonstrated to promote longevity. In addition, aging and longevity genes are disrupted in various circadian disorders. Our study indicates that the modulation of circadian-affected tissue specificity is essential for understanding the circadian mechanisms that regulate aging and longevity at the genomic level.
2024-06-03 | GSE240689 | GEO
Project description:ObjectivesTo study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α.MethodsParticipants 50 to 95 years of age from the Mayo Clinic Study of Aging were assigned age- and sex-specific multi-morbidity percentiles using look-up tables that were reported previously (n = 1646). Percentiles were divided into quintiles for analysis. Plasma IL-6, IL-10, and TNF-α levels were measured in 1595 participants. Median inflammatory marker levels were compared across multi-morbidity quintiles using nonparametric tests.ResultsPeople with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles.ConclusionsMulti-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.
| S-EPMC9274410 | biostudies-literature
Project description:Ovarian cancer is one of three major malignancies of the female reproductive system. DNA methylation (MET) is closely related to ovarian cancer occurrence and development, and as such, elucidation of effective MET subtype markers may guide individualized treatment and improve ovarian cancer prognosis. To identify potential markers, we downloaded a total of 571 ovarian cancer MET samples from The Cancer Genome Atlas (TCGA), and established a Cox proportional hazards model using the MET spectrum and clinical pathological parameters. A total of 250 prognosis-related MET loci were obtained by Cox regression, and six molecular subtypes were screened by consensus clustering of CpG loci with a significant difference in both univariate and multivariate analyses. There was a remarkable MET difference between most subtypes. Cluster 2 had the highest MET level and demonstrated the best prognosis, while Clusters 4 and 5 had MET levels significantly lower than those of the other subtypes and demonstrated very poor prognosis. All Cluster 5 samples were at a high grade, while the percentage of stage IV samples in Cluster 4 was greater than in the other subtypes. We obtained five CpG loci using a coexpression network: cg27625732, cg00431050, cg22197830, cg03152385, and cg22809047. Our cluster analysis showed that prognosis in patients with hypomethylation was significantly worse than in patients with hypermethylation. These MET molecular subtypes can be used not only to evaluate ovarian cancer prognosis, but also to fully distinguish the tumor stage and histological grade in patients with ovarian cancer.
| S-EPMC7931230 | biostudies-literature
Project description:The X-linked ribosomal protein S4 (RPS4X), which is involved in cellular translation and proliferation, has previously been identified as a partner of the overexpressed multifunctional protein YB-1 in several breast cancer cells. Depletion of RPS4X results in consistent resistance to cisplatin in such cell lines.As platinum-based chemotherapy is a standard first line therapy used to treat patients with ovarian cancer, we evaluated the prognostic value of RPS4X and YB-1 at the protein level in specimen from 192 high-grade serous epithelial ovarian cancer patients.Immunohistochemistry studies indicated that high expression of RPS4X was associated with a lower risk of death and later disease progression (HR?=?0.713, P?=?0.001 and HR?=?0.761, P?=?0.001, respectively) as compared to low expression of RPS4X. In contrast, YB-1 was not significantly associated with either recurrence or survival time in this cohort. Finally, the depletion of RPS4X with different siRNAs in two different ovarian cancer cell lines reduced their proliferative growth rate but more importantly increased their resistance to cisplatin.Altogether, these results suggest that the levels of RPS4X could be a good indicator for resistance to platinum-based therapy and a prognostic marker for ovarian cancer. Our study also showed that RPS4X is an independent prognostic factor in patients with serous epithelial ovarian cancer.
| S-EPMC3708827 | biostudies-other
Project description:B-cell translocation gene 3 (BTG3) is a member of the BTG family which inhibits cell proliferation, metastasis, and angiogenesis, and also regulates cell-cycle progression and differentiation in a variety of cell types. However, there is no study to analyze BTG3 expression in epithelial ovarian carcinoma (EOC). Here, we investigated the expression of BTG3 in EOC carcinogenesis and subsequent progression. BTG3 mRNA expression was detected by real-time RT-PCR in ovarian benign and malignant tumors. The expression of BTG3 protein was examined by immunohistochemistry on tissue microarrays containing ovarian normal tissue, benign and borderline epithelial ovarian tumors, and EOCs. Relationships of BTG3 with both EOC clinicopathology and prognosis were analyzed statistically. The expression of BTG3 protein was also evaluated in ovarian normal tissue, benign tumors, and EOCs by western blot. The BTG3 mRNA expression level was higher in ovarian normal tissue and benign tumors than that in borderline, primary, and metastatic carcinoma (p < 0.05), and was negatively correlated with dedifferentiation and FIGO staging of EOC (p < 0.05). Using western blot, BTG3 protein was found lower in EOCs compared to the normal and benign tumors (p < 0.05), and poorly differentiated EOCs showed lower BTG3 expression than well-differentiated and moderately differentiated EOCs (p < 0.05). Immunohistochemically, BTG3 protein expression was statistically lower in EOCs than normal tissue and benign tumors (p < 0.05). EOC patients with low BTG3 protein expression showed a higher incidence of metastasis (p = 0.020), poor differentiation (p = 0.030), and shorter disease-free time and overall survival time (p < 0.05). By using Cox's proportional hazard model, BTG3 protein expression and FIGO staging were independent prognostic factors for both disease-free time and overall survival time of EOCs (p < 0.05). It was suggested that down-regulated BTG3 expression might play roles in the pathogenesis and aggressiveness of EOC. BTG3 protein expression may be considered as a good marker to indicate the favorable prognosis of EOCs.
| S-EPMC3785705 | biostudies-literature