Article Abstract

An assessment of candidate genes to assist prognosis in gastric cancer

Authors: Michael McFarlane, Julia Brettschneider, Adrian Gelsthorpe, Sean James, David Snead, Kishore Gopalakrishnan, Hisham Mehenna, Janusz Jankowski, Ramesh Arasaradnam, Chuka Nwokolo


Background: Gastric cancer (GC) is the fourth commonest cancer worldwide, with the second highest mortality rate. Its poor mortality is linked to delayed presentation. There is a drive towards non-invasive biomarker screening and monitoring of many different types of cancer, although with limited success so far. We aimed to determine if any genes from a 32-gene panel could be used to determine GC prognosis.
Methods: We carried out a retrospective study on the expression of 32 genes, selected for their proven or potential links to GC, on historic formalin fixed paraffin-embedded (FFPE) GC specimens from our unit. Gene expression was measured using quantitative nuclease protection assays (qNPA) technology. Following statistical analysis of the results, immunohistochemical staining for eight genes, both discriminating and nondiscriminating, was conducted in seven age and sex matched non-metastatic: metastatic GC pairings. The stained samples were reviewed by two blinded consultant histopathologists.
Results: Multivariate Cox analysis of the gene expression data revealed metastatic status, age, sex and five genes appeared to influence GC survival. Genes negatively influencing survival included BCAS1, P53 and HSP90AA1 (relative risks 2.20, 3.73 and 7.53 respectively). Genes conveying survival benefit included CASP3 and TERT (relative risks 0.10 and 0.24 respectively). Immunohistochemical staining of seven age and sex matched nonmetastatic: metastatic pairs revealed no association between gene expression and protein expression.
Conclusions: Our study found several genes whose expression may affect GC prognosis. However, immunohistochemical analysis revealed no association between gene expression and protein expression. It remains to be determined whether gene expression or protein expression are reliable means of assessing GC prognosis.