Abstract
Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis compared to moderately differentiated (MD) and well differentiated (WD) HCC. We aimed to identify differentially expressed genes (DEGs) to explore the mechanism of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non-tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus identified and functionally analyzed. Further RT-PCR was performed to validate DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for WD). A total of 681 PD DEGs were detected, including 368 up-regulated and 313 down-regulated genes. Less DEGs were found for MD and especially for WD HCC. Through bioinformatics analysis, PD HCC DEGs were enriched in liver tissue and liver cancer cells, and in biological process and pathway including metabolism, cell cycle, translation and blood coagulation. Potential drugs and genetic perturbations were found to reverse the cancer condition. The RT-PCR results showed consistency with RNA-seq in the validation of 4 DEGs specific for PD HCC. This study detected and validated DEGs of PD HCC, which provides useful information on molecular mechanism of PD HCC for development of new biomarkers, therapeutic targets and drugs.
Highlights
As one of the most common malignancies worldwide, hepatocellular carcinoma (HCC) represents the second-leading cause of cancer deaths globally with 745,000 deaths per year [1]
Poorly differentiated (PD) HCC differentially expressed genes (DEGs) were enriched in liver tissue and liver cancer cells, and in biological process and pathway including metabolism, cell cycle, translation and blood coagulation
The number of DEGs for poorly differentiated HCC is significantly bigger than that of other two stages. Those DEGs are enriched in liver tissue and cells, which is understood
Summary
As one of the most common malignancies worldwide, hepatocellular carcinoma (HCC) represents the second-leading cause of cancer deaths globally with 745,000 deaths per year [1]. The HCC were categorized into poorly-, moderately-, and well- differentiated types. Hepatic resection is currently the most optimal choice for HCC treatment. Poorly differentiated HCC has a worse prognosis with high recurrence rate compared to other two types [2, 3]. It is hard to discriminate poorly differentiated HCC from other two types of HCC before treatment. The lack of good diagnostic markers and therapeutic targets has rendered HCC a major challenge
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