A Multi-omics Study on the Oncogenic Roles and Clinical Significance of Dynactin Family Gene (DCTN1-6) Expression in Liver Hepatocellular Carcinoma

In this study, we employed a comprehensive database mining approach to examine the possible oncogenic roles and clinical relevance of Dynactin family genes (DCTN1-6) in Liver Hepatocellular Carcinoma (LIHC). All the DCTNs were observed to be differentially expressed in LIHC tissues compared to the adjacent normal liver tissues. Most of the DCTNs were discovered to be aberrantly methylated (less methylated) and contain multiple somatic mutations (alteration frequency: 0.2-2.5%) in LIHC tissues. Overexpression of DCTNs was mostly associated with poor overall and relapse-free survival of LIHC patients. Alongside, all the DCTN genes were reported to be overexpressed across different demographic and clinical conditions, i.e., age, cancer stage, tumor grades, and metastatic stages of LIHC patients. DCTN expression was also associated with the infiltration levels of different immune cells, i.e., B cell, T cell, and macrophages in LIHC microenvironment. The co-expressed genes of DCTNs in the LIHC tissues were previously found to be involved in oncogenic processes in different cancer types and control crucial biological processes, i.e., nucleotide metabolism, RNA degradation, and chromosome organization. Later, the expression pattern of DCTNs was validated in two independent microarray datasets (i.e., GSE17856, GSE98383), which also supported our initial findings. All these findings suggest that DCTNs and their transcriptional and translational products are potential prognostic and therapeutic targets for LIHC diagnosis and treatment. This study will help further the development of DCTN-based diagnostic and therapeutic measures for LIHC and translate them into clinical implications.