Diagnostic values of GHSR DNA methylation pattern in breast cancer

Botla, Sandeep K.; Gholami, Amin Moghaddas; Malekpour, Mahdi; Moskalev, Evgeny A.; Fallah, Mahdi; Jandaghi, Pouria; Aghajani, Ali; Bondar, Irina S.; Omranipour, Ramesh; Malekpour, Fatemeh; Mohajeri, Abbas; Babadi, Azin Jahangiri; Şahin, Özgür; Бубнов, В. В.; Najmabadi, Hossein; Hoheisel, Jörg D.; Riazalhosseini, Yasser

doi:10.1007/s10549-012-2197-z

Cited by 17 publications

(19 citation statements)

References 37 publications

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“…At cellular level, we observed a restoration of SFRP4 expression in pituitary adenoma cells (GH3) after treatment with the demethylating agent, 5-aza-2 V-deoxycytidine. These findings are consistent with studies conducted on various other malignancies, including gastric, cervical, hepatocellular, pancreatic, oral squamous cell, breast, colon, and bladder cancers (44)(45)(46)(47)(48)(49).…”

Section: Discussionsupporting

confidence: 91%

Assessment of sFRP4 as a bio-marker for predicting aggressiveness and recurrence of growth hormone-secreting pituitary adenomas

Liu

et al. 2016

Oncology Reports

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The association of sFRP4 expression with aggressiveness and recurrence of growth hormone (GH)-secreting pituitary adenomas was investigated. Ten normal pituitary and 52 GH-secreting pituitary adenoma specimens were classified into three groups: normal pituitary (control) group, non-aggressive group, and aggressive group, according to preoperative evaluation by magnetic resonance imaging (MRI)/computed tomography (CT). Expression of sFRP4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and tissue microarrays, to assess the association between sFRP4 and aggressiveness. Follow-up information of all 52 patients was collected to evaluate the impact of sFRP4 expression on the recurrence/progression of GH-secreting pituitary adenomas. qRT-PCR results showed a lower level of sFRP4 mRNA in the aggressive group, as compared to that in the non-aggressive group (P=0.001). A similar trend was observed on western blot analysis for sFRP4 protein expression (P=0.004). On analysis by tissue microarrays, weak sFRP4 expression was detected in the aggressive group (10/15, 66.7%). Univariate analysis showed a significant relationship between low sFRP4 expression and aggressiveness (P=0.024). On multivariate analysis weak sFRP4 expression was found to be an independent factor of recurrence/progression (odds ratio: 0.063, P=0.026). Methylation of the sFRP4 promoter was increased in low sFRP4 staining group compared to that in the high sFRP4 staining group (P<0.001). In this study, weak sFRP4 expression appeared to predict aggressive behavior, and was associated with recurrence/progression of GH-secreting pituitary adenomas. Methylation of the sFRP4 promoter may account for the low sFRP4 expression.

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Section: Discussionsupporting

confidence: 91%

Assessment of sFRP4 as a bio-marker for predicting aggressiveness and recurrence of growth hormone-secreting pituitary adenomas

Liu

et al. 2016

Oncology Reports

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“…Indeed, expression of the cognate GHSR GHSR1a could even be reduced in breast cancer samples compared with normal mammary gland (Gahete et al 2011a). In line with this, it has been suggested that the hypermethylation of the GHSR promoter region could be the underlying cause of this phenomenon, as hypermethylation is a frequent hallmark observed in primary breast tumor (Ordway et al 2007) and its levels are negatively associated with GHSR1a expression (Botla et al 2012).…”

Section: Adrenal Tumorsmentioning

confidence: 88%

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

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Ghrelin is a 28-amino acid acylated hormone, highly expressed in the stomach, which binds to its cognate receptor (GHSR1a) to regulate a plethora of relevant biological processes, including food intake, energy balance, hormonal secretions, learning, inflammation, etc. However, ghrelin is, in fact, the most notorious component of a complex, intricate regulatory system comprised of a growing number of alternative peptides (e.g. obestatin, unacylated ghrelin, and In1-ghrelin, etc.), known (GHSRs) and, necessarily unknown receptors, as well as modifying enzymes (e.g. ghrelin-O-acyl-transferase), which interact among them as well as with other regulatory systems in order to tightly modulate key (patho)-physiological processes. This multiplicity of functions and versatility of the ghrelin system arise from a dual, genetic and functional, complexity. Importantly, a growing body of evidence suggests that dysregulation in some of the components of the ghrelin system can lead to or influence the development and/or progression of highly concerning pathologies such as endocrine-related tumors, inflammatory/cardiovascular diseases, and neurodegeneration, wherein these altered components could be used as diagnostic, prognostic, or therapeutic targets. In this context, the aim of this review is to integrate and comprehensively analyze the multiple components and functions of the ghrelin system described to date in order to define and understand its biological and (patho)-physiological significance.

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“…5 In an earlier study, we had found DNA hypermethylation in the promoter of the growth hormone secretagouge receptor (GHSR) gene as an epigenetic marker of highest accuracy for detection of breast cancer. 6 This finding was supported by analyzing tumors as well as an extensive list of control samples including normal-appearing tissue samples from cancer patients and healthy individuals, as well as benign lesions. The gene promoter was significantly hypermethylated in both invasive and non-invasive in situ ductal breast cancer as compared to other samples.…”

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confidence: 85%