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Expression of the Aldo-Ketoreductases AKR1B1 and AKR1B10 in Human Cancers.

Laffin B, Petrash JM - Front Pharmacol (2012)

Bottom Line: Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver.AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas.High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, The School of Medicine, University of Colorado Aurora, CO, USA.

ABSTRACT
The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-ketoreductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com). Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

No MeSH data available.


Related in: MedlinePlus

AKR gene expression and clinical outcome. The relationship between AKR1B1 and AKR1B10 mRNA expression and clinical outcomes were examined using the Oncomine database. (A) Comparison of AKR1B1 expression in acute myeloid leukemia patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (B) Comparison of AKR1B1 expression in multiple myeloma patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (C) AKR1B10 expression relative to clinical outcome in liver cancer and squamous cell lung cancer. Colored boxes are a heatmap-style representation of AKR1B10 expression in patients dead relative to those alive at 3 years post diagnosis, with blue indicating under-expression and red over-expression. Median rank and p-value for this panel considers all indicated studies simultaneously.
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Figure 3: AKR gene expression and clinical outcome. The relationship between AKR1B1 and AKR1B10 mRNA expression and clinical outcomes were examined using the Oncomine database. (A) Comparison of AKR1B1 expression in acute myeloid leukemia patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (B) Comparison of AKR1B1 expression in multiple myeloma patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (C) AKR1B10 expression relative to clinical outcome in liver cancer and squamous cell lung cancer. Colored boxes are a heatmap-style representation of AKR1B10 expression in patients dead relative to those alive at 3 years post diagnosis, with blue indicating under-expression and red over-expression. Median rank and p-value for this panel considers all indicated studies simultaneously.

Mentions: We next asked whether expression of AKRs might be able to predict clinical outcome, specifically in terms of patient survival, disease recurrence, tumor grade, and metastasis. We found no significant associations with expression of AKR1B1 and the presence of metastasis, tumor grade, or with disease recurrence in any cancer type, though some individual studies sometimes contained a significant relationship that did not hold up when all available data for that cancer type was considered (data not shown). AKR1B1 over-expression was associated with decreased patient survival at 1 year post-prognosis in acute myeloid leukemias (Figure 3A), as well as decreased patient survival at 1 year post-prognosis in multiple myeloma (Figure 3B). AKR1B1 over-expression was also associated with decreased survival in pancreatic cancer, however, only one small study (27 patients) within Oncomine contained patient survival data (data not shown). While no significant associations of patient survival with AKR1B10 expression were observed, it is noteworthy that in the solid tumors where AKR1B10 is most highly over-expressed, namely liver cancer and squamous cell lung carcinoma, there is a strong trend for AKR1B10 over-expression predicting longer patient survival (Figure 3C).


Expression of the Aldo-Ketoreductases AKR1B1 and AKR1B10 in Human Cancers.

Laffin B, Petrash JM - Front Pharmacol (2012)

AKR gene expression and clinical outcome. The relationship between AKR1B1 and AKR1B10 mRNA expression and clinical outcomes were examined using the Oncomine database. (A) Comparison of AKR1B1 expression in acute myeloid leukemia patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (B) Comparison of AKR1B1 expression in multiple myeloma patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (C) AKR1B10 expression relative to clinical outcome in liver cancer and squamous cell lung cancer. Colored boxes are a heatmap-style representation of AKR1B10 expression in patients dead relative to those alive at 3 years post diagnosis, with blue indicating under-expression and red over-expression. Median rank and p-value for this panel considers all indicated studies simultaneously.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368246&req=5

Figure 3: AKR gene expression and clinical outcome. The relationship between AKR1B1 and AKR1B10 mRNA expression and clinical outcomes were examined using the Oncomine database. (A) Comparison of AKR1B1 expression in acute myeloid leukemia patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (B) Comparison of AKR1B1 expression in multiple myeloma patients who were alive (blue boxes) and dead (red boxes) at 1 year post diagnosis. Individual p-values are indicated within each box plot and the p-value and median gene rank for all three studies is at the right of the panel. (C) AKR1B10 expression relative to clinical outcome in liver cancer and squamous cell lung cancer. Colored boxes are a heatmap-style representation of AKR1B10 expression in patients dead relative to those alive at 3 years post diagnosis, with blue indicating under-expression and red over-expression. Median rank and p-value for this panel considers all indicated studies simultaneously.
Mentions: We next asked whether expression of AKRs might be able to predict clinical outcome, specifically in terms of patient survival, disease recurrence, tumor grade, and metastasis. We found no significant associations with expression of AKR1B1 and the presence of metastasis, tumor grade, or with disease recurrence in any cancer type, though some individual studies sometimes contained a significant relationship that did not hold up when all available data for that cancer type was considered (data not shown). AKR1B1 over-expression was associated with decreased patient survival at 1 year post-prognosis in acute myeloid leukemias (Figure 3A), as well as decreased patient survival at 1 year post-prognosis in multiple myeloma (Figure 3B). AKR1B1 over-expression was also associated with decreased survival in pancreatic cancer, however, only one small study (27 patients) within Oncomine contained patient survival data (data not shown). While no significant associations of patient survival with AKR1B10 expression were observed, it is noteworthy that in the solid tumors where AKR1B10 is most highly over-expressed, namely liver cancer and squamous cell lung carcinoma, there is a strong trend for AKR1B10 over-expression predicting longer patient survival (Figure 3C).

Bottom Line: Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver.AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas.High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, The School of Medicine, University of Colorado Aurora, CO, USA.

ABSTRACT
The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-ketoreductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com). Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

No MeSH data available.


Related in: MedlinePlus