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The use of variations in proteomes to predict, prevent, and personalize treatment for clinically nonfunctional pituitary adenomas.

Zhan X, Desiderio DM - EPMA J (2010)

Bottom Line: Unlike functional pituitary adenomas, nonfunctional (NF) pituitary adenomas account for ∼30% of pituitary tumors, and are large enough to cause blindness; because they do not cause any clinical hormone hypersecretion, they are difficult to detect at an early stage; and hypopituitarism results.No effective molecular biomarkers or chemical therapy have been approved for the clinical setting.Changes in protein expression and protein modifications, individually or in combination, might be biomarkers to predict the disease, monitor the tumor progression, and develop an accurate molecular classification for personalized patient treatment.

View Article: PubMed Central - PubMed

Affiliation: Charles B. Stout Neuroscience Mass Spectrometry Laboratory, The University of Tennessee Health Science Center, 847 Monroe Avenue, Room 117, Memphis, TN 38163 USA.

ABSTRACT
Pituitary adenomas account for ∼10% of intracranial tumors, and they cause the compression of nearby structures and the inappropriate expression of pituitary hormones. Unlike functional pituitary adenomas, nonfunctional (NF) pituitary adenomas account for ∼30% of pituitary tumors, and are large enough to cause blindness; because they do not cause any clinical hormone hypersecretion, they are difficult to detect at an early stage; and hypopituitarism results. No effective molecular biomarkers or chemical therapy have been approved for the clinical setting. Because an NF pituitary adenoma is highly heterogeneous, differences in the proteins (the proteome) can distinguish among those heterogeneity structures. The components of a proteome dynamically change as an NF adenoma progresses. Changes in protein expression and protein modifications, individually or in combination, might be biomarkers to predict the disease, monitor the tumor progression, and develop an accurate molecular classification for personalized patient treatment. The modalities of proteomic variation might also be useful in the interventional prevention and personalized treatment of patients to halt the occurrence and progression of NF pituitary adenomas.

No MeSH data available.


Related in: MedlinePlus

Expression proportion of the four splicing isoforms of GH in human pituitary glands. Reproduced from Zhan and Desiderio [24], with permission from Wiley-VCH, copyright 2005
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Fig4: Expression proportion of the four splicing isoforms of GH in human pituitary glands. Reproduced from Zhan and Desiderio [24], with permission from Wiley-VCH, copyright 2005

Mentions: The heterogeneity of hormone expression is an important characteristic in an NF pituitary adenoma. Protein isoforms result from protein PTMs, splicing, etc. A comparative proteomics study of NF adenomas demonstrated that two hormones (GH and PRL) had multiple isoforms [1, 23]. Twenty-four 2D gel spots that contained GH were found in control pituitary tissues [24] (Fig. 3). Those hGHs in the 24 2D gel spots were classified into four types of hGH-splicing isoforms, 1–4. The expression proportion of those four isoforms were isoform 1 (87.5 %) > isoform 2 (8.1 %) > isoform 3 (3.3 %) > isoform 4 (1.1 %) (Fig. 4); and a significant statistical difference was found among those isoforms. Not all of isoforms related to NF pituitary adenomas [1]. Somatotropin was significantly down-regulated at the protein and the mRNA levels in the NF pituitary adenoma [1] and in prolactinomas [23]; that finding is consistent with their monoclonal origin [2, 3]—an NF adenoma originated from gonadotrophs, and a prolactinoma from lactotrophs; the GH receptor gene was unchanged. Those data showed that GH hyposecretion in an NF-adenoma results from the hypo-expression of the GH gene. However, the more important finding is that the multiple GH isoforms (17 spots contain somatotropin) were detected [1, 23]; those data cannot be interpreted from transcriptomics data. The down-regulated ratio of the different GH isoforms was different in each cell-type of NF pituitary adenoma relative to the controls. Those data suggested that the proportion of the different GH isoforms changed in each cell-type NF adenoma compared to controls. Other researchers showed that the proportion of a circulating GH isoform significantly changed in pituitary adenomas and other pituitary diseases [25, 26]. The proportional change of the different GH isoforms might have an important value in the clinical evaluation of NF adenomas. Recently, studies found that GH isoforms were derived from a variety of splicing variants and PTMs, including phosphorylation [24]. The phosphorylation of endogenous GH in the human pituitary [27] provided new insights into the mechanisms of GH that participate in the neuroendocine signal pathways.Fig. 3


The use of variations in proteomes to predict, prevent, and personalize treatment for clinically nonfunctional pituitary adenomas.

Zhan X, Desiderio DM - EPMA J (2010)

Expression proportion of the four splicing isoforms of GH in human pituitary glands. Reproduced from Zhan and Desiderio [24], with permission from Wiley-VCH, copyright 2005
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3405333&req=5

Fig4: Expression proportion of the four splicing isoforms of GH in human pituitary glands. Reproduced from Zhan and Desiderio [24], with permission from Wiley-VCH, copyright 2005
Mentions: The heterogeneity of hormone expression is an important characteristic in an NF pituitary adenoma. Protein isoforms result from protein PTMs, splicing, etc. A comparative proteomics study of NF adenomas demonstrated that two hormones (GH and PRL) had multiple isoforms [1, 23]. Twenty-four 2D gel spots that contained GH were found in control pituitary tissues [24] (Fig. 3). Those hGHs in the 24 2D gel spots were classified into four types of hGH-splicing isoforms, 1–4. The expression proportion of those four isoforms were isoform 1 (87.5 %) > isoform 2 (8.1 %) > isoform 3 (3.3 %) > isoform 4 (1.1 %) (Fig. 4); and a significant statistical difference was found among those isoforms. Not all of isoforms related to NF pituitary adenomas [1]. Somatotropin was significantly down-regulated at the protein and the mRNA levels in the NF pituitary adenoma [1] and in prolactinomas [23]; that finding is consistent with their monoclonal origin [2, 3]—an NF adenoma originated from gonadotrophs, and a prolactinoma from lactotrophs; the GH receptor gene was unchanged. Those data showed that GH hyposecretion in an NF-adenoma results from the hypo-expression of the GH gene. However, the more important finding is that the multiple GH isoforms (17 spots contain somatotropin) were detected [1, 23]; those data cannot be interpreted from transcriptomics data. The down-regulated ratio of the different GH isoforms was different in each cell-type of NF pituitary adenoma relative to the controls. Those data suggested that the proportion of the different GH isoforms changed in each cell-type NF adenoma compared to controls. Other researchers showed that the proportion of a circulating GH isoform significantly changed in pituitary adenomas and other pituitary diseases [25, 26]. The proportional change of the different GH isoforms might have an important value in the clinical evaluation of NF adenomas. Recently, studies found that GH isoforms were derived from a variety of splicing variants and PTMs, including phosphorylation [24]. The phosphorylation of endogenous GH in the human pituitary [27] provided new insights into the mechanisms of GH that participate in the neuroendocine signal pathways.Fig. 3

Bottom Line: Unlike functional pituitary adenomas, nonfunctional (NF) pituitary adenomas account for ∼30% of pituitary tumors, and are large enough to cause blindness; because they do not cause any clinical hormone hypersecretion, they are difficult to detect at an early stage; and hypopituitarism results.No effective molecular biomarkers or chemical therapy have been approved for the clinical setting.Changes in protein expression and protein modifications, individually or in combination, might be biomarkers to predict the disease, monitor the tumor progression, and develop an accurate molecular classification for personalized patient treatment.

View Article: PubMed Central - PubMed

Affiliation: Charles B. Stout Neuroscience Mass Spectrometry Laboratory, The University of Tennessee Health Science Center, 847 Monroe Avenue, Room 117, Memphis, TN 38163 USA.

ABSTRACT
Pituitary adenomas account for ∼10% of intracranial tumors, and they cause the compression of nearby structures and the inappropriate expression of pituitary hormones. Unlike functional pituitary adenomas, nonfunctional (NF) pituitary adenomas account for ∼30% of pituitary tumors, and are large enough to cause blindness; because they do not cause any clinical hormone hypersecretion, they are difficult to detect at an early stage; and hypopituitarism results. No effective molecular biomarkers or chemical therapy have been approved for the clinical setting. Because an NF pituitary adenoma is highly heterogeneous, differences in the proteins (the proteome) can distinguish among those heterogeneity structures. The components of a proteome dynamically change as an NF adenoma progresses. Changes in protein expression and protein modifications, individually or in combination, might be biomarkers to predict the disease, monitor the tumor progression, and develop an accurate molecular classification for personalized patient treatment. The modalities of proteomic variation might also be useful in the interventional prevention and personalized treatment of patients to halt the occurrence and progression of NF pituitary adenomas.

No MeSH data available.


Related in: MedlinePlus