Журнал канцерогенеза и мутагенеза

Абстрактный

Gene Expression Meta-Analysis of Colon Rectal Cancer Tumour Cells Reveals Genes in Association with Tumourigenesis

Rutvi Vaja

Background: Every year, more than 12 million people are diagnosed with colorectal cancer (CRC), and more than 600,000 people die from it, making it second most deadly form of cancer.This work analyzes differential gene expression across CRC and other glandular tumour samples to identify expression changes potentially contributing to the development of CRC tumourigenesis.

Methods: This work defines 13 gene signatures representing four CRC tumour and 10 other glandular tumours that are colonic by origin. Gene Set Enrichment Analysis (GSEA) is used to define positive and negative CRC gene panels from GSEA-identified leading-edge genes using two CRC signatures. GSEA then is used to verify enrichment and leading-edge gene membership of CRC panels in two independent CRC gene signatures. Analysis is then extended to four individual and 10 glandular tumour signatures. Genes most associated with CRC tumourigenesis are predicted by intersecting membership of GSEA-identified leading-edges across signatures.

Results: Significant enrichment is observed between CRC gene identification signatures, from which the positive (55 genes) and negative (77 genes) CRC panels are defined. Non-random significant enrichment is observed between CRC gene panels and verification signatures, from which 54 overand 72 under-expressed genes are shared across leading-edges. Considering other glandular tumour samples individually and in combination with CRC, significant non-random enrichment is observed across these signatures. Eight solute carrier family genes such as (SLC25A32, SLC22A3, SLC25A20, SLC36A1, SLC26A3, SLC9A2, SLC4A4 and SLC26A2) from the CRC panel were shared commonly across all the gene signatures leading-edges, regardless of the colonic tumour type.

Conclusion: This meta-analysis identifies gene expression changes associated with the process of CRC tumourigenesis. These changes may contribute to developing therapeutic treatments available for CRC patients.