Identification of personalized dysregulated pathways in hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common liver malignancy, and ranks the fifth most prevalent malignant tumors worldwide. In general, HCC are detected until the disease is at an advanced stage and may miss the best chance for treatment. Thus, elucidating the molecular mechanisms is critical to clinical diagnosis and treatment for HCC. The purpose of this study was to identify dysregulated pathways of great potential functional relevance in the progression of HCC.

MATERIALS AND METHODS: Microarray data of 72 pairs of tumor and matched non-tumor surrounding tissues of HCC were transformed to gene expression data. Differentially expressed genes (DEG) between patients and normal controls were identified using Linear Models for Microarray Analysis. Personalized dysregulated pathways were identified using individualized pathway aberrance score module.

RESULTS: 169 differentially expressed genes (DEG) were obtained with |logFC|≥1.5 and P≤0.01. 749 dysregulated pathways were obtained with P≤0.01 in pathway statistics, and there were 93 DEG overlapped in the dysregulated pathways. After performing normal distribution analysis, 302 pathways with the aberrance probability≥0.5 were identified. By ranking pathway with aberrance probability, the top 20 pathways were obtained. Only three DEGs (TUBA1C, TPR, CDC20) were involved in the top 20 pathways.

CONCLUSION: These personalized dysregulated pathways and overlapped genes may give new insights into the underlying biological mechanisms in the progression of HCC. Particular attention can be focused on them for further research.