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Distinct prognostic values and potential drug targets of ALDH1 isoenzymes in non-small-cell lung cancer.

You Q, Guo H, Xu D - Drug Des Devel Ther (2015)

Bottom Line: Increased aldehyde dehydrogenase 1 (ALDH1) activity has been found in the stem cell populations of leukemia and some solid tumors including non-small-cell lung cancer (NSCLC).However, which ALDH1's isoenzymes are contributing to ALDH1 activity remains elusive.In addition, high expression of ALDH1A1 mRNA was also found to be correlated to better OS in adenocarcinoma (Ade) patients (HR 0.71 [0.57-0.9], P=0.0044) but not in squamous cell carcinoma (SCC) patients (HR 0.92 [0.72-1.16], P=0.48).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.

ABSTRACT
Increased aldehyde dehydrogenase 1 (ALDH1) activity has been found in the stem cell populations of leukemia and some solid tumors including non-small-cell lung cancer (NSCLC). However, which ALDH1's isoenzymes are contributing to ALDH1 activity remains elusive. In addition, the prognostic value of individual ALDH1 isoenzyme is not clear. In the current study, we investigated the prognostic value of ALDH1 isoenzymes in NSCLC patients through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information from a total of 1,926 NSCLC patients. High expression of ALDH1A1 mRNA was found to be correlated to a better overall survival (OS) in all NSCLC patients followed for 20 years (hazard ratio [HR] 0.88 [0.77-0.99], P=0.039). In addition, high expression of ALDH1A1 mRNA was also found to be correlated to better OS in adenocarcinoma (Ade) patients (HR 0.71 [0.57-0.9], P=0.0044) but not in squamous cell carcinoma (SCC) patients (HR 0.92 [0.72-1.16], P=0.48). High expression of ALDH1A2 and ALDH1B1 mRNA was found to be correlated to worser OS in all NSCLC patients, as well as in Ade, but not in SCC patients. High expression of both ALDH1A3 and ALDH1L1 mRNA was not found to be correlated to OS in all NSCLC patients. These results strongly support that ALDH1A1 mRNA in NSCLC is associated with better prognosis. In addition, our current study also supports that ALDH1A2 and ALDH1B1 might be major contributors to the ALDH1 activity in NSCLC, since high expression of ALDH1A2 and ALDH1B1 mRNA was found to be significantly correlated to worser OS in all NSCLC patients. Based on our study, ALDH1A2 and ALDH1B1 might be excellent potential drug targets for NSCLC patients.

No MeSH data available.


Related in: MedlinePlus

The prognostic value of ALDH1L1 expression.Notes: The desired Affymetrix ID is valid: 205208_at (ALDH1L1). (A) Survival curves are plotted for all patients (n=1,926). (B) Survival curves are plotted for adenocarcinoma (n=719). (C) Survival curves are plotted for squamous cell carcinoma (n=525). Data was analyzed using Kaplan Meier Plotter (www.kmplot.com).Abbreviation: HR, hazard ratio.
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f5-dddt-9-5087: The prognostic value of ALDH1L1 expression.Notes: The desired Affymetrix ID is valid: 205208_at (ALDH1L1). (A) Survival curves are plotted for all patients (n=1,926). (B) Survival curves are plotted for adenocarcinoma (n=719). (C) Survival curves are plotted for squamous cell carcinoma (n=525). Data was analyzed using Kaplan Meier Plotter (www.kmplot.com).Abbreviation: HR, hazard ratio.

Mentions: Finally, we examined the prognostic value of ALDH1L1 mRNA expression in www.kmplot.com. The desired Affymetrix ID is valid: 205208_at (ALDH1L1). The curves show that ALDH1L1 expression above or below the median does not separate the cases into significantly different prognostic groups in NSCLC patients (HR 1.1 [0.97–1.25], P=0.13) (Figure 5A) or Ade patients (HR 1.19 [0.94–1.5], P=0.14) (Figure 5B), or SCC patients (HR 0.87 [0.69–1.1], P=0.26) (Figure 5C).


Distinct prognostic values and potential drug targets of ALDH1 isoenzymes in non-small-cell lung cancer.

You Q, Guo H, Xu D - Drug Des Devel Ther (2015)

The prognostic value of ALDH1L1 expression.Notes: The desired Affymetrix ID is valid: 205208_at (ALDH1L1). (A) Survival curves are plotted for all patients (n=1,926). (B) Survival curves are plotted for adenocarcinoma (n=719). (C) Survival curves are plotted for squamous cell carcinoma (n=525). Data was analyzed using Kaplan Meier Plotter (www.kmplot.com).Abbreviation: HR, hazard ratio.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562757&req=5

f5-dddt-9-5087: The prognostic value of ALDH1L1 expression.Notes: The desired Affymetrix ID is valid: 205208_at (ALDH1L1). (A) Survival curves are plotted for all patients (n=1,926). (B) Survival curves are plotted for adenocarcinoma (n=719). (C) Survival curves are plotted for squamous cell carcinoma (n=525). Data was analyzed using Kaplan Meier Plotter (www.kmplot.com).Abbreviation: HR, hazard ratio.
Mentions: Finally, we examined the prognostic value of ALDH1L1 mRNA expression in www.kmplot.com. The desired Affymetrix ID is valid: 205208_at (ALDH1L1). The curves show that ALDH1L1 expression above or below the median does not separate the cases into significantly different prognostic groups in NSCLC patients (HR 1.1 [0.97–1.25], P=0.13) (Figure 5A) or Ade patients (HR 1.19 [0.94–1.5], P=0.14) (Figure 5B), or SCC patients (HR 0.87 [0.69–1.1], P=0.26) (Figure 5C).

Bottom Line: Increased aldehyde dehydrogenase 1 (ALDH1) activity has been found in the stem cell populations of leukemia and some solid tumors including non-small-cell lung cancer (NSCLC).However, which ALDH1's isoenzymes are contributing to ALDH1 activity remains elusive.In addition, high expression of ALDH1A1 mRNA was also found to be correlated to better OS in adenocarcinoma (Ade) patients (HR 0.71 [0.57-0.9], P=0.0044) but not in squamous cell carcinoma (SCC) patients (HR 0.92 [0.72-1.16], P=0.48).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.

ABSTRACT
Increased aldehyde dehydrogenase 1 (ALDH1) activity has been found in the stem cell populations of leukemia and some solid tumors including non-small-cell lung cancer (NSCLC). However, which ALDH1's isoenzymes are contributing to ALDH1 activity remains elusive. In addition, the prognostic value of individual ALDH1 isoenzyme is not clear. In the current study, we investigated the prognostic value of ALDH1 isoenzymes in NSCLC patients through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information from a total of 1,926 NSCLC patients. High expression of ALDH1A1 mRNA was found to be correlated to a better overall survival (OS) in all NSCLC patients followed for 20 years (hazard ratio [HR] 0.88 [0.77-0.99], P=0.039). In addition, high expression of ALDH1A1 mRNA was also found to be correlated to better OS in adenocarcinoma (Ade) patients (HR 0.71 [0.57-0.9], P=0.0044) but not in squamous cell carcinoma (SCC) patients (HR 0.92 [0.72-1.16], P=0.48). High expression of ALDH1A2 and ALDH1B1 mRNA was found to be correlated to worser OS in all NSCLC patients, as well as in Ade, but not in SCC patients. High expression of both ALDH1A3 and ALDH1L1 mRNA was not found to be correlated to OS in all NSCLC patients. These results strongly support that ALDH1A1 mRNA in NSCLC is associated with better prognosis. In addition, our current study also supports that ALDH1A2 and ALDH1B1 might be major contributors to the ALDH1 activity in NSCLC, since high expression of ALDH1A2 and ALDH1B1 mRNA was found to be significantly correlated to worser OS in all NSCLC patients. Based on our study, ALDH1A2 and ALDH1B1 might be excellent potential drug targets for NSCLC patients.

No MeSH data available.


Related in: MedlinePlus