Controversial role of the possible oxyntic stem cell marker ASPM in gastric cancer.

We read with great interest the article by Vange et al [1] in the December 2015 issue of the Journal of Pathology, as well as the subsequent commentary by Zhu et al in the January 2016 issue [2]. Vange et al identified a novel possible oxyntic stem/progenitor cell marker ASPM [Asp (abnormal spindle) homologue, microcephaly-associated (Drosophila)] by genome-wide expression analysis of the microdissected isthmus zone, where the majority of stem/progenitor cells are believed to reside. ASPM was also overexpressed in gastric cancer and correlated with its possible transcription factor E2F1 at the mRNA level. In our analysis of the microarray dataset GSE13911, ASPM was also highly expressed in gastric tumour tissues, indicating its role in carcinogenesis (p< 0.001 for all three ASPM-oriented probes) (Figure 1). Meanwhile, as ASPM is a stem cell marker, we hypothesized that tumours with high expression of ASPM should be more poorly differentiated than those with low expression. However, we found that tumours with poor differentiation showed significantly lower expression of ASPM than those with moderate differentiation (p= 0.0204) (Figure 2). This result was based on IlluminaHiseq RNA-sequencing data from 421 stomach adenocarcinomas from the TGCA database. Thus, we thought that ASPM might play a different role in gastric cancer. To validate our result, we used the Kaplan–Meier Plotter online tool (http://kmplot.com/analysis/) to identify the role of ASPM in the prognosis of gastric cancer. Surprisingly, patients with high expression of ASPM in gastric cancer showed a better prognosis than those with low expression (p< 0.001 for all three ASPM-oriented probes) (Figure 3). Conversely, high expression of ASPM was related to poor prognosis in both lung and breast cancers, but was not significant in ovarian cancer. Regarding its coexpressed transcription factor E2F1, high expression was also related to poor prognosis (p< 0.001 for both E2F1-oriented probes) (Figure 4). Although the authors demonstrated an association between ASPM and E2F1 in gastric cancer, owing to their common involvement in crucial cell fate-regulatory mechanisms, these results indicate different roles for ASPM and E2F1 in the prognosis of gastric cancer. In conclusion, the current evidence could not confirm ASPM as a novel oxyntic stem/progenitor cell marker, and its role in gastric cancer is controversial. Further well-designed studies are needed to identify the role of Figure 1. ASPM expression in gastric cancer and adjacent normal tissues.