Abstract
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.
Highlights
Gastric cancer (GC), one of the serious threats to human health contributing to a malignant tumor in the digestive system, is currently the third most common cause of deaths associated with cancer worldwide, accounting for approximately 9% of cancer-related deaths [1]
ONCOMINE analysis of 6 Aldehyde dehydrogenase 1 (ALDH1) sub-members in cancer vursus. normal samples showed that ALDH1A1 was significantly downregulated in different types of GC in different datasets
The ALDH1A1 mRNA level was decreased in diffuse gastric adenocarcinoma (Figure 2C) and gastric intestinal type adenocarcinoma (Figure 2D), compared with gastric mucosa [19, 20]
Summary
Gastric cancer (GC), one of the serious threats to human health contributing to a malignant tumor in the digestive system, is currently the third most common cause of deaths associated with cancer worldwide, accounting for approximately 9% of cancer-related deaths [1]. Only a handful of new chemotherapeutic agents or moleculartargeted therapies have been developed. Further investigations in the underlining mechanisms of incidence and progression, as well as determining the development of prognosis and treatment biomarkers, will provide a comprehensive picture of their impacts on survival and invaluable reference allowing new agents/therapies. It is reported that CSC is responsible for the renewal of tumor mass after systemic treatment and development of sub-clones with more resistance to chemotherapeutics [5]. Many protein are reported to be the putative gastric cancer CSC markers, such as CD26 [6], CD44 [7], ALDH1 [8], and CD133 [9], and Lgr, which was reported to be co-localized with other CSC markers and may be functionally-associated [10]
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