Ovarian cancer (OC) is the deadliest among all gynecological cancers. Epidemiological studies showed that obesity might influence many cancers including OC. One of the key factors that may link obesity and OC is leptin (LEP), known as an adipokine with pleiotropic effects on body homeostasis. This study aims to investigate the expression pattern of LEP, assess the methylation profiles of LEP and their associations with clinicopathological features including survival outcomes of OC patients. The protein expression of LEP was evaluated in 208 samples using both tissue microarray and immunohistochemistry techniques. The methylation profiles of LEP were measured in 63 formalin-fixed, paraffin-embedded tumor tissues by quantitative polymerase chain reaction using a MethyLight assay. Our results showed a significant association of LEP protein overexpression with several clinicopathological variables, mainly tumor subtype, LVI, age of menarche, tumor size and stage (p < 0.04). Kaplan–Meier analysis (using low expression versus high expression as a discriminator) indicated that LEP protein overexpression is a powerful positive prognosticator of both OC recurrence (DFS) and disease-specific survival (DSS) in our OC cohort (log-rank p = 0.01 and p = 0.002, respectively). This implies that patients with high LEP expression profiles live longer with less recurrence rates. Methylation analysis results demonstrated a clear association between no/low LEP protein expression pattern (38%) and LEP promoter CpG island hypermethylation (43%). Results of this study suggest that LEP is a powerful prognosticator of OC recurrence and DSS. LEP expression in OC seems to be regulated by its promoter hypermethylation through gene partial/total silencing. Further multi-institutional studies using larger cohorts are required to demystify the intricate molecular functions of this leptin-driven effects in OC pathophysiology and to accurately assess its theranostic potential and validate its prognostic/predictive power in OC onset, progression towards more effective and personalized management of OC patients.
Background: Biobanking is a critical cornerstone of the global shift towards precision medicine (PM). This transformation requires smooth and informed interaction between a range of stakeholders involved in the healthcare system. In Saudi Arabia, there is still insufficient awareness of the importance of biobanking and its potential benefits for patients, the healthcare system, and society as a whole. The purpose of this study was to determine the biobanking knowledge of Saudi healthcare providers and the potential factors that might influence their self-reported attitudes toward biospecimen donation and biobanking. Methods: A cross-sectional study was conducted targeting 636 healthcare providers in Makkah province using a structured, self-administered questionnaire. Results: The study had a response rate of 61%. The mean knowledge level about biobanks was 3.5 (±1.8) out of 7. About one-third of the participants were aware of the Human Genome Project (HGP) (35%) or the term “biobank” (34%). The mean rating of their attitude was 37.3 (±4.3) out of 55. Most participants (74%) had a positive attitude toward medical research. Job position, general health, previous blood tests, knowledge of biobanking, and attitudes toward biomedical research were significantly related and predictors of willingness to donate biospecimens (p < 0.05). However, concerns about biospecimen misuse and confidentiality were the main reasons for not donating biospecimens. Conclusions: This study has shown that healthcare providers mostly lack basic knowledge about HGP and biobanks and their roles and activities, and therefore are generally disinclined to actively participate in biospecimens’ collection and management. It is recommended that medical trainees receive more education and awareness about biobanks and the latest personalized healthcare approaches to improve translational research outcomes and achieve precision medicine.
Among all gynecological cancers, ovarian cancer (OC) is one of the deadliest types of cancer worldwide. Epigenetic silencing of some genes has been reported to be associated with OC. In this context, Klotho (KL) gene methylation is a promising biomarker for OC. The present study aimed to investigate the methylation profiles of KL and assess its prognostic value. A total of 63 formalin-fixed paraffin-embedded tissue samples from patients with primary OC were collected and analyzed in the present study. The methylation profiles of KL were assessed by performing DNA bisulfate treatment followed by DNA promoter methylation analysis using the MethyLight assay. The results revealed KL promoter hypermethylation in 62% of the OC cohort. Additionally, significant associations were observed between KL methylation profiles and tumor subtype (P<0.0001) and tumor site (P=0.039). Furthermore, Kaplan-Meier analysis revealed that a worse disease-specific survival was significantly associated with hypermethylated KL (P=0.03, log-rank; hazard ration, 0.58; 95% confidence interval (CI), 0.26-0.90). Cox regression multivariate analysis indicated that KL promoter methylation was an independent OC prognostic indicator (P=0.029). The current study suggested that KL may be a novel biomarker to predict prognosis in patients with OC, since patients with higher KL promoter methylation were more likely to have a poor prognosis and would therefore require frequent follow-up and integrative personalized therapeutic approaches.
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