Dys-regulated Gene Expression Networks by Meta-Analysis of Microarray Data on Oral Squamous Cell Carcinoma

Abstract

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common type of carcinoma worldwide. Development of OSCC is a multi-step process involving genes related to cell cycle, growth control, apoptosis, DNA damage response and other cellular regulators. The pathogenic pathways involved in this tumor are mostly unknown and therefore a better characterization of OSCC gene expression profile would represent a considerable advance. The availability of publicly available gene expression datasets has opened up new challenges especially for the integration of data gener- ated by different research groups and different array platforms with the purpose of obtaining new in- sights on the biological process investigated. Results: In this work we performed a meta-analysis on four microarray and four datasets of gene ex- pression data on OSCC in order to evaluate the degree of agreement of the biological results obtained by these different studies and to identify common regulatory pathways that could be responsible of tumor growth. Sixteen dys-regulated pathways implicated in OSCC were mined out from the four pub- lished datasets, and most importantly three pathways were first reported. Those regulatory pathways and biological processes which are significantly enriched have been investigated by means of litera- tures and meanwhile, four genes of the maximally altered pathways, ECM-receptor interaction, were validated and identified by qRT-PCR as a possible candidate of aggressiveness of OSCC. Conclusion: we have developed a robust method for analyzing pathways altered in OSCC using three expression array data sets. Although this method has been used on four microarray studies, it can be extended to multiple expression array data sets. This study sets a stage for the further discovery of the basic mechanisms that may underlie a diseased state and would help in identifying critical nodes in the pathway that can be targeted for diagnosis and therapeutic intervention. In addition, those who are interested in our approach can obtain the software package (MATLAB platform) by email freely.