J Cancer 2020; 11(7):1869-1882. doi:10.7150/jca.39163 This issue
1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
2. Department of Medical Cosmetology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Province, China.
3. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Province, China.
4. Department of Health Management and Division of Physical Examination, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
5. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
Background: Hepatocellular carcinoma (HCC) has high morbidity and mortality and lacks effective biomarkers for early diagnosis and survival surveillance. Origin recognition complex (ORC), consisting of ORC1-6 isoforms, was examined to assess the potential significance of ORC isoforms for HCC prognosis.
Methods: Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to examine differential isoform expression, stage-specific expression, calculate Pearson correlations and perform survival analysis. A human protein atlas database was utilized to evaluate the protein expression of ORCs in liver tissue. The cBioPortal database was used to assess isoform mutations and the survival significance of ORCs in HCC. Cytoscape software was employed to construct gene ontologies, metabolic pathways and gene-gene interaction networks.
Results: Differential expression analysis indicated that ORC1 and ORC3-6 were highly expressed in tumor tissues in the Oncomine and GEPIA databases, while ORC2 was not. All the ORCs were showed positive and statistically significant correlations with each other (all P<0.001). ORC1-2 and ORC4-6 expressions were associated with disease stages I-IV (all P<0.05), but ORC3 was not. Survival analysis found that ORC1 and ORC4-6 expressions were associated with overall survival (OS), and ORC1-3 and ORC5-6 expression were associated with recurrence-free survival (RFS; all P<0.05). In addition, low expression of these ORC genes consistently indicated better prognosis compared with high expression. Protein expression analysis revealed that ORC1 and ORC3-6 were expressed in normal liver tissues, whereas ORC2 was not. Enrichment analysis indicated that ORCs were associated with DNA metabolic process, sequence-specific DNA binding and were involved in DNA replication, cell cycle, E2F-enabled inhibition of pre-replication complex formation and G1/S transition.
Conclusions: Differentially expressed ORC1, 5 and 6 are candidate biomarkers for survival prediction and recurrence surveillance in HCC.
Keywords: origin recognition complex, ORC1, ORC5, ORC6, biomarker, hepatocellular carcinoma.