Differential expression of aristaless-like homeobox 4: a potential marker for gastric adenocarcinoma
Aim: Gastric cancer is the second most common cancer all over the world, approximately responsible for 3% to 10% of all cancer-related deaths. The identification of biomarkers may improve the diagnosis and treatment of gastric cancer. Recent publications declared Aristaless-Like Homeobox 4 (ALX-4) expression levels to be up-regulated in multiple tumors. These results were intriguing for a variety of reasons. This article explores, for the first time, examined the ALX-4 mRNA level in different grades of human Gastric adenocarcinoma comparatively, in gastric cancer stem cell (GCSC) as well as MKN-45 cell line.
Methods: MKN-45 cell culture prepared, and gastric cancer stem cell (GCSC) isolation and identification performed by flowcytometry and then 37 fresh gastric cancer patients tissue sample were subjected for expression analysis with quantitative real-time PCR, prior to any therapeutic intervention in the comparative study for evaluation of ALX-4 gene expression.
Results: gastric cancer stem cell with cuboidal shape and positive expression for CD105, CD44, CD90 and negative for CD45, CD34 were identified. Overexpression of ALX-4 was detected in 46% (3.351±2.94, P<0.05) of gastric cancer tissue specimens and Significant high expression level of ALX-4in GCSCs (4.31±0.04, P<0.005). The mRNA expression level of ALX-4 in MKN-45 gastric cancer cell line was 2.81±0.07 (P<0.005). ALX-4 mRNA level significantly correlation with tumor grad (P=0.004), stage (p=0.000153) and relationship with gender (P= 0.06).
Conclusion: These sets of results documented the important role of ALX-4 in GCSCs as an indicated oncogenic role in progressive cancer and valuable target in treatment of drug resistant tumors.