Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Assidi, Mourad; Yahya, Fatimah M.; Al-Zahrani, Maryam H.; Elkhatib, Razan; Zari, Ali; Elaimi, Aisha; Al‐Maghrabi, Jaudah; Dallol, Ashraf; Buhmeida, Abdelbaset; Abu‐Elmagd, Muhammad

doi:10.3390/ijms222312872

Cited by 14 publications

(10 citation statements)

References 89 publications

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“…This was also supported by the findings that a chronic low level of inflammation is associated with obesity, and contributes to BC by damaging the DNA [44]. Moreover, cell proliferation in BC is due to the production of excessive amounts of estrogen and adipokines from fat cells [43,45,46].…”

Section: Discussionmentioning

confidence: 62%

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach

Sharhan

Messaoudi

Babu

et al. 2022

Genes

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The diagnostic and prognostic utility of circulating cell-free DNA (cfDNA) in breast cancer (BC) patients was recently reported. Here, we investigated the use of cfDNA to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) for early BC diagnosis. cfDNA and genomic DNA from 41 female BC patients and 40 healthy controls were quantified using NanoDrop spectrophotometry and real-time PCR. The stability of genomic and cfDNA was assessed using a high-resolution AmpFlSTR MiniFiler human identification kit. Significant increases in cfDNA plasma concentrations were observed in BC patients compared to controls. The genotype distribution of the eight autosomal short tandem repeat (STR) loci D7S820, D13S317, D21S11, D2S1338, D18S51, D16S539, FGA, and CSF1PO were in Hardy–Weinberg equilibrium. Significant differences in the allele frequencies of D7S820 allele-8, D21S11 allele-29, allele-30.2, allele-32.2, and CSF1PO allele-11 were seen between BC patients and controls. LOH and MSI were detected in 36.6% of the cfDNA of patients compared to genomic DNA. This study highlights the utility of plasma-derived cfDNA for earlier, less invasive, and cost-effective cancer diagnosis and molecular stratification. It also highlights the potential value of cfDNA in molecular profiling and biomarkers discovery in precision and forensic medicine.

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Section: Discussionmentioning

confidence: 62%

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach

Sharhan

Messaoudi

Babu

et al. 2022

Genes

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“…Its best-known biological role is to signal satiety to the hypothalamus and subsequently reduce food intake and fat storage. Leptin was shown to promote cancer progression and metastasis by regulating the EMT, cell adhesion to the extracellular matrix (ECM), and proteolysis of the ECM compounds [ 59 , 60 ]. Although leptin’s expression is common in most OC cells and is associated with higher aggressiveness and poorer treatment outcome [ 59 , 60 ], circulating leptin levels are usually lower in presence of OC compared to benign tumors [ 28 , 29 , 61 , 62 ], as could also be observed in our setting.…”

Section: Discussionmentioning

confidence: 99%

Biomarker-Based Models for Preoperative Assessment of Adnexal Mass: A Multicenter Validation Study

Watrowski

Obermayr

Wallisch

et al. 2022

Cancers

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Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and our earlier Proteomic Model 2017. Biomarkers were assessed using bead-based multiplex technology (Luminex®) in 356 women (250 with malignant and 106 with benign ovarian tumors) from five European centers. The training cohort included 279 women from three centers, and the validation cohort 77 women from two other centers. Of six previously studied serum proteins (CA125, HE4, osteopontin [OPN], prolactin, leptin, and macrophage migration inhibitory factor [MIF]), four contributed significantly to the Proteomic Model 2021 (CA125, OPN, prolactin, MIF), while leptin and HE4 were omitted by the algorithm. The Proteomic Model 2021 revealed a c-index of 0.98 (95% CI 0.96, 0.99) in the training cohort; however, in the validation cohort it only achieved a c-index of 0.82 (95% CI 0.72, 0.91). Adding patient age to the Proteomic Model 2021 constituted the Combined Model 2021, with a c-index of 0.99 (95% CI 0.97, 1) in the training cohort and a c-index of 0.86 (95% CI 0.78, 0.95) in the validation cohort. The Full Combined Model 2021 (all six proteins with age) yielded a c-index of 0.98 (95% CI 0.97, 0.99) in the training cohort and a c-index of 0.89 (95% CI 0.81, 0.97) in the validation cohort. The validation of our previous Proteomic Model 2017, as well as the ROMA-50 and CPH-I revealed a c-index of 0.9 (95% CI 0.82, 0.97), 0.54 (95% CI 0.38, 0.69) and 0.92 (95% CI 0.85, 0.98), respectively. In postmenopausal women, the three newly developed models all achieved a specificity of 1.00, a positive predictive value (PPV) of 1.00, and a sensitivity of >0.9. Performance in women under 50 years of age (c-index below 0.6) or with normal CA125 (c-index close to 0.5) was poor. CA125 and OPN had the best discriminating power as single markers. In summary, the CPH-I, the two combined 2021 Models, and the Proteomic Model 2017 showed satisfactory diagnostic accuracies, with no clear superiority of either model. Notably, although combining values of only four proteins with age, the Combined Model 2021 performed comparably to the Full Combined Model 2021. The models confirmed their exceptional diagnostic performance in women aged ≥50. All models outperformed the ROMA-50.

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“…As in breast and endometrial cancer, leptin has been studied in relationship to cancer progression, metastases, and chemoresistance in ovarian cancer 141,142 . Isolated studies have identified leptin as a biomarker for disease although further randomized assessments are needed to validate these findings 143,144 . Leptin signaling via the JAK/STAT3 pathway upregulates ERα transcriptional activation, mediating ovarian cancer progression 141 .…”

Section: Methodsmentioning

confidence: 99%

The impact of obesity and adipokines on breast and gynecologic malignancies

Tewari

Vargas

Reizes

2022

Annals of the New York Academy of Sciences

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The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer‐related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat‐secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity–cancer link has amassed, we now know that additional adipokines can impact tumorigenesis. A deeper understanding of the adipokine‐activated signaling in cancer may identify new treatment strategies irrespective of obesity. Moreover, adipokines may serve as disease biomarkers, harnessing the potential of obesity‐associated factors to serve as indicators of treatment response and disease prognosis. As studies investigating obesity and women's cancers continue to expand, it has become evident that breast, ovarian, and uterine cancers are distinctly impacted by adipokines. While complex, these distinct interactions may provide insight into cancer progression in these organs and new opportunities for targeted therapies. This review aims to organize and present the literature from the last 5 years investigating the mechanisms and implications of adipokine signaling in breast, endometrial, and ovarian cancers with a special focus on leptin and adiponectin.

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Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Cited by 14 publications

References 89 publications

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach

Biomarker-Based Models for Preoperative Assessment of Adnexal Mass: A Multicenter Validation Study

The impact of obesity and adipokines on breast and gynecologic malignancies

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