Analysis of Prediagnostic Circulating Levels of Gonadotropins and Androgens with Risk of Epithelial Ovarian Cancer.

Background Prevailing experimental and epidemiological evidence supports the role of circulating endogenous sex steroid hormones in the pathogenesis of ovarian carcinogenesis by dysregulation of cell differentiation, proliferation, and apoptosis but is scarce and inconclusive. Objectives This article evaluates the role of circulating levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and androgens (testosterone, dehydroepiandrosterone-sulfate [DHEA-S]) for the risk of epithelial ovarian cancer in a case-control approach using samples collected in advance of clinical diagnosis. Materials and Methods A total of 100 epithelial ovarian cancer (EOC) patients and 100 healthy female controls were consequently enrolled in this hospital-based case-control study. Serum FSH, LH, testosterone, and DHEA-S were measured based on the principle of electrochemiluminescence immunoassay. Suitable descriptive statistics were used for different variables. Results Median values of FSH (58.9 vs. 45.5 IU/L, p = 0.02) and DHEA-S (163.43 vs. 142.2 ug/dL, p = 0.03) were significantly high in EOC patients compared with controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH and DHEA-S concentrations, and the results revealed that the highest third tertile of FSH (> 72.6 IU/L; OR = 3.0, confidence interval [CI] = 1.24-7.29, p trend = 0.04) and DHEA-S (> 194.2 ug/dL; OR = 3.8, CI = 1.26-11.61, p trend = 0.03) were significantly associated with increased risk of ovarian cancer in postmenopausal and premenopausal women, respectively. The statistically significant trend observed for FSH in postmenopausal women, remained only for the subgroup with menopause duration greater than 10 years (OR = 5.9, CI = 1.33-26.66, p trend = 0.04). FSH and DHEA-S concentrations and ovarian cancer risk were internally consistent with groups defined by oral contraceptive pill use, hormone replacement therapy, and smoking. However, no evidence was found for the association between serum LH and testosterone level with the occurrence of ovarian tumorigenesis. Conclusion Prediagnostic circulating concentration of FSH and DHEA-S unveiled a significant positive association with augmented risk of EOC, thus might serve as a predictive marker for the susceptibility to ovarian carcinogenesis and should be added in the screening profile of EOC for early recognition and scheduling necessary interventions/management strategies.

NGAL/MMP-9 as a Biomarker for Epithelial Ovarian Cancer: A Case-Control Diagnostic Accuracy Study.

Background: Epithelial ovarian cancer (EOC) are often diagnosed late due to lack of specific symptoms and efficient tumor markers. Neutrophil gelatinase-associated lipocalin/matrix metallopeptidase-9 (NGAL/MMP-9) complex are involved in the development and progression of various cancers and have potential as a biomarker for diagnosing ovarian cancer. Objectives: To compare the serum NGAL/MMP-9 complex levels in patients with EOC, benign ovarian tumor, and healthy controls, and determine the potential cut-off values of NGAL/MMP-9 complex for diagnosing EOC. Materials and Methods: The study included 50 patients each with EOC and benign ovarian tumor, along with 50 age-matched healthy controls (N = 150). The level of serum NGAL/MMP-9 complex was estimated based on sandwich ELISA. The mean and median of the three groups were compared, and the ROC curve was used to determine the optimum cut-off, sensitivity, and specificity of serum NGAL/MMP-9 complex levels in the diagnosis of EOC. Results: A significant difference was found in the median values of the NGAL/MMP-9 complex (malignant EOC: 67.5 ng/ml, benign ovarian tumor: 53.7 ng/ml, controls: 29.2 ng/ml; P < 0.01). NGAL/MMP-9 complex level was also significantly associated with the FIGO staging (Stages I and II: 42.9 ng/ml; Stages III and IV: 70.5 ng/ml; P < 0.003). At a 55.0 ng/ml cut-off value, the NGAL/MMP-9 complex had 82.0% sensitivity and 78.0% specificity in diagnosing EOC. Conclusion: The NGAL/MMP-9 complex may be a promising biomarker for determining the progression of EOC as well as in detecting advanced-stage ovarian cancer.

CRISPR/Cas9: A Molecular Tool for Ovarian Cancer Management beyond Gene Editing.

Ovarian cancer manifests with early metastases and has an adverse outcome, impacting the health of women globally. Currently, this malignancy is often treated with cytoreductive surgery and platinum-based chemotherapy. This treatment option has a limited success rate due to tumor recurrence and chemoresistance. Consequently, the fundamental objective of ovarian cancer treatment is the development of novel treatment approaches. As a new robust tool, the CRISPR/Cas9 gene-editing system has shown immense promise in elucidating the molecular basis of all the facets of ovarian cancer. Due to the precise gene editing capabilities of CRISPR-Cas9, researchers have been able to conduct a more comprehensive investigation of the genesis of ovarian cancer. This gained knowledge can be translated into the development of novel diagnostic approaches and newer therapeutic targets for this dreadful malignancy. There is encouraging preclinical evidence that suggests that CRISPR/Cas9 is a powerful versatile tool for selectively targeting cancer cells and inhibiting tumor growth, establishing new signaling pathways involved in carcinogenesis, and verifying biomolecules as druggable targets. In this review, we analyzed the current research and progress made using CRISPR/Cas9-based engineering strategies in the diagnosis and treatment, as well as the challenges in bringing this method to clinics. This comprehensive analysis will lay the basis for subsequent research in the future for the treatment of ovarian cancer.

Role of the Tumor Microenvironment and the Influence of Epigenetics on the Tumor Microenvironment in Oral Carcinogenesis: Potential Implications.

Oral cancer has become a significant problem throughout the world, particularly in countries that are still developing. Recent literature supports the contribution of components of the tumor microenvironment (TME) and the effect of epigenetic changes happening in the cells of the TME on oral cancer development and progression. In this review, we comprehensively examine the significance of TME in the development of OC along with the current understanding of the epigenetic modifications that regulate the TME and their cohesive impact on tumor traits and their potential as therapeutic targets.