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An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species.

Rybaczyk LA, Bashaw MJ, Pathak DR, Huang K - BMC Genomics (2008)

Bottom Line: Previous work has produced promising results such as the identification of p53.Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man.Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. rybaczyk.1@osu.edu

ABSTRACT

Background: Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types.

Results: Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls.

Conclusion: These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.

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Related in: MedlinePlus

Expression of MAO-A in normal and cancer tissue samples. Tissues are from humans (H), mice (Mus musculus, M), rats (Rattus norvegicus, R), or zebrafish (Danio rerio, Z). Values are included for each dataset with independent samples in both human and animal models. Although all analyses were conducted on raw MAO-A expression levels, here we show both normal (white bars) and cancer (black bars) expression levels as a percentage of the mean expression in normal tissue within that data set. Control and cancer MAO-A expression levels are significantly different for all of the cancer types shown. Error bars indicate standard error of the mean.
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Figure 1: Expression of MAO-A in normal and cancer tissue samples. Tissues are from humans (H), mice (Mus musculus, M), rats (Rattus norvegicus, R), or zebrafish (Danio rerio, Z). Values are included for each dataset with independent samples in both human and animal models. Although all analyses were conducted on raw MAO-A expression levels, here we show both normal (white bars) and cancer (black bars) expression levels as a percentage of the mean expression in normal tissue within that data set. Control and cancer MAO-A expression levels are significantly different for all of the cancer types shown. Error bars indicate standard error of the mean.

Mentions: By conducting a series of analyses focusing on tryptophan related gene expression data (see Table 1 for a list of genes analyzed) in the GEO database (gene expression omnibus) maintained by NCBI [22], we found that only Monoamine Oxidase A (MAO-A, E.C. 1.4.3.4) showed consistent decreased expression, in cancers among a variety of tissues from humans, rodents, and zebrafish. Specifically, only MAO-A expression was significantly altered in all 13 of the datasets that used non-cancerous patients as controls and half of the paired datasets. Table 2 provides specific p-values and the mean fold change in MAO-A for the datasets analyzed. Although the extent of downregulation varied among patients, cumulatively 95.4% of all of the tissue samples from human cancer patients, and 94.2% of all animal cancer cases showed lower MAO-A expression than the single lowest control sample in their respective dataset. Changes in expression for unpaired data are provided in Figure 1.


An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species.

Rybaczyk LA, Bashaw MJ, Pathak DR, Huang K - BMC Genomics (2008)

Expression of MAO-A in normal and cancer tissue samples. Tissues are from humans (H), mice (Mus musculus, M), rats (Rattus norvegicus, R), or zebrafish (Danio rerio, Z). Values are included for each dataset with independent samples in both human and animal models. Although all analyses were conducted on raw MAO-A expression levels, here we show both normal (white bars) and cancer (black bars) expression levels as a percentage of the mean expression in normal tissue within that data set. Control and cancer MAO-A expression levels are significantly different for all of the cancer types shown. Error bars indicate standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2311292&req=5

Figure 1: Expression of MAO-A in normal and cancer tissue samples. Tissues are from humans (H), mice (Mus musculus, M), rats (Rattus norvegicus, R), or zebrafish (Danio rerio, Z). Values are included for each dataset with independent samples in both human and animal models. Although all analyses were conducted on raw MAO-A expression levels, here we show both normal (white bars) and cancer (black bars) expression levels as a percentage of the mean expression in normal tissue within that data set. Control and cancer MAO-A expression levels are significantly different for all of the cancer types shown. Error bars indicate standard error of the mean.
Mentions: By conducting a series of analyses focusing on tryptophan related gene expression data (see Table 1 for a list of genes analyzed) in the GEO database (gene expression omnibus) maintained by NCBI [22], we found that only Monoamine Oxidase A (MAO-A, E.C. 1.4.3.4) showed consistent decreased expression, in cancers among a variety of tissues from humans, rodents, and zebrafish. Specifically, only MAO-A expression was significantly altered in all 13 of the datasets that used non-cancerous patients as controls and half of the paired datasets. Table 2 provides specific p-values and the mean fold change in MAO-A for the datasets analyzed. Although the extent of downregulation varied among patients, cumulatively 95.4% of all of the tissue samples from human cancer patients, and 94.2% of all animal cancer cases showed lower MAO-A expression than the single lowest control sample in their respective dataset. Changes in expression for unpaired data are provided in Figure 1.

Bottom Line: Previous work has produced promising results such as the identification of p53.Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man.Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. rybaczyk.1@osu.edu

ABSTRACT

Background: Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types.

Results: Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls.

Conclusion: These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.

Show MeSH
Related in: MedlinePlus