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Genetic aspects of pituitary carcinoma: A systematic review

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs, the prognosis is poor and 66% of patients die within the first year. Existing therapeutic measures, including surgical removal, chemotherapy, and radiotherapy, have limited effectiveness. The lack of efficacy of current treatments is largely caused by the limited understanding of the molecular pathogenesis of PA and the malignant transformation to PC. Therefore, the aim of this systematic review was to summarize published research regarding gene and protein expression in PC to clarify the molecular mechanisms underlying PC genesis and development and identify new candidate diagnostic biomarkers and therapeutic targets for potential use in personalized treatment of PC.

Methods:: We followed the PRISMA guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of Science databases were searched for relevant studies conducted before December 16, 2015 describing the association of PC with gene expression at the mRNA and protein levels. MeSH terms combined with free terms were used to retrieve the references.

Results:: In total, 207 records were obtained by primary search, and 32 were included in the systematic review. Compared with normal pituitary gland and/or PA, 30 and 18 genes were found to have higher or lower expression, respectively, in PCs using different analytical methods. Among them, we selected 9 upregulated and 7 downregulated genes for further analysis based on their identification as candidate treatment targets in other cancers, potential clinical application, or further research value.

Conclusion:: Previous studies demonstrated that many genes promote PC malignant transformation, angiogenesis, invasion, metastasis, and recurrence. Although most of these genes and proteins have not been fully analyzed with regard to their downstream mechanisms or potential diagnostic and therapeutic application, they have the potential to become candidate PC biomarkers and/or molecular targets for guiding personalized treatment. Modern advanced technologies should be utilized in future research to identify more candidate genes for PC pathogenesis, as precisely targeted gene therapies against PC are urgently required.

No MeSH data available.


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Mentions: Our analysis identified several important genes and corresponding proteins involved in malignant transformation, growth, recurrence, metastasis, angiogenesis, and apoptosis in pituitary neoplasms (Table 2). Upregulation of cyclin D1, VEGF, MMP-9, miRNAs, and p21Cip1 showed a clear correlation with tumor cell cycle progression, vasculogenesis, metastasis, and invasion, and may contribute to malignant transformation of PAs to PCs. Downregulated factors such as MGMT, p16Ink4A, p27Kip1, Bcl-2, Bax, Bcl-x, and MT3 are involved in the cell cycle, apoptosis, tumor suppression, metabolism, and enhanced TMZ sensitivity. Figure 2 presents a schematic diagram showing the functions of the selected genes and proteins in PCs. These pathways suggest that the development and progress of PCs results from a multistage process with multigene mutations, similar to the pathogenesis of other cancers. Further research should more extensively evaluate the identified genes to provide a further understanding of the malignant transformation in PCs, and to validate these genes as candidate diagnostic markers and therapeutic targets in pituitary neoplasms.


Genetic aspects of pituitary carcinoma: A systematic review
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5134857&req=5

Mentions: Our analysis identified several important genes and corresponding proteins involved in malignant transformation, growth, recurrence, metastasis, angiogenesis, and apoptosis in pituitary neoplasms (Table 2). Upregulation of cyclin D1, VEGF, MMP-9, miRNAs, and p21Cip1 showed a clear correlation with tumor cell cycle progression, vasculogenesis, metastasis, and invasion, and may contribute to malignant transformation of PAs to PCs. Downregulated factors such as MGMT, p16Ink4A, p27Kip1, Bcl-2, Bax, Bcl-x, and MT3 are involved in the cell cycle, apoptosis, tumor suppression, metabolism, and enhanced TMZ sensitivity. Figure 2 presents a schematic diagram showing the functions of the selected genes and proteins in PCs. These pathways suggest that the development and progress of PCs results from a multistage process with multigene mutations, similar to the pathogenesis of other cancers. Further research should more extensively evaluate the identified genes to provide a further understanding of the malignant transformation in PCs, and to validate these genes as candidate diagnostic markers and therapeutic targets in pituitary neoplasms.

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs, the prognosis is poor and 66% of patients die within the first year. Existing therapeutic measures, including surgical removal, chemotherapy, and radiotherapy, have limited effectiveness. The lack of efficacy of current treatments is largely caused by the limited understanding of the molecular pathogenesis of PA and the malignant transformation to PC. Therefore, the aim of this systematic review was to summarize published research regarding gene and protein expression in PC to clarify the molecular mechanisms underlying PC genesis and development and identify new candidate diagnostic biomarkers and therapeutic targets for potential use in personalized treatment of PC.

Methods:: We followed the PRISMA guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of Science databases were searched for relevant studies conducted before December 16, 2015 describing the association of PC with gene expression at the mRNA and protein levels. MeSH terms combined with free terms were used to retrieve the references.

Results:: In total, 207 records were obtained by primary search, and 32 were included in the systematic review. Compared with normal pituitary gland and/or PA, 30 and 18 genes were found to have higher or lower expression, respectively, in PCs using different analytical methods. Among them, we selected 9 upregulated and 7 downregulated genes for further analysis based on their identification as candidate treatment targets in other cancers, potential clinical application, or further research value.

Conclusion:: Previous studies demonstrated that many genes promote PC malignant transformation, angiogenesis, invasion, metastasis, and recurrence. Although most of these genes and proteins have not been fully analyzed with regard to their downstream mechanisms or potential diagnostic and therapeutic application, they have the potential to become candidate PC biomarkers and/or molecular targets for guiding personalized treatment. Modern advanced technologies should be utilized in future research to identify more candidate genes for PC pathogenesis, as precisely targeted gene therapies against PC are urgently required.

No MeSH data available.