Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer
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Jia-Xin Shen1,*, Jing Liu2,3,*, Guan-Wu Li4, Yi-Teng Huang5, Hua-Tao Wu1
1Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, PR China
2Chang Jiang Scholar’s Laboratory, Shantou University Medical College, Shantou, PR China
3Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou, PR China
4Open Laboratory for Tumor Molecular Biology/Department of Biochemistry, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, PR China
5Health Care Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, PR China
*These authors contributed equally to this work
Hua-Tao Wu, email: [email protected]
Keywords: ALDH1, gastric cancer, prognosis, KM plotter, hazard ratio (HR)
Received: October 27, 2015 Accepted: March 10, 2016 Published: March 23, 2016
Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database. Through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information of 876 GC patients, we also investigated the prognostic values of ALDH1 isoenzymes in GC patients. It was found that when compared with normal tissues, ALDH1A1 mRNA expression was downregulated, whereas ALDH1A3 and ALDH1B1 were upregulated in GC patients. In survival analyses, high ALDH1A1 and ALDH1B1 expressions were associated with better overall survival (OS) in all GC patients. In addition, high transcription activity of ALDH1A1 predicted better OS in gastric intestinal type adenocarcinoma, but not in diffuse gastric adenocarcinoma. GC patients with high mRNA level of ALDH1B1 showed better OS in gastric intestinal type, and worse OS in diffuse type. Oppositely, high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in GC patients, suggesting that these isoenzymes might be responsible mainly for the ALDH1 activities in GC. These data provides ALDH1A2, ALDH1A3 and ALDH1L1 as excellent potential targets for individualized treatment of GC patients.
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