DNA Replication Regulator ORCs in Lung Adenocarcinomas

Patients with lung adenocarcinoma (LUAD) is characterized by DNA replication alteration, which is typically seen during LUAD development. Origin recognition complex (ORC) 1, ORC 2, ORC 3, ORC 4, ORC 5, and ORC 6 form a replication-initiator complex to mediate DNA replication, which is essential for the development of cancer. However, their functions in LUAD are yet unclear.

The GEPIA, HPA, CPTAC, and TCGA databases confirmed the mRNA and protein expression of ORCs. The GeneMANIA database examined the network of protein-protein interactions. The Metascape database confirmed functional enrichment. The TIMER database confirmed the impact of ORCs on immunological infiltration. The KM-plot and GENT2 databases verified the predictive importance of ORCs in LUAD. The cBioProtal and PDB databases were used to detect DNA change and protein structure. Additionally, immunohistochemistry (IHC) staining was used to corroborate the protein expression and predictive usefulness of ORCs in the LUAD data sets.

Individuals with LUAD had considerably higher levels of ORC mRNA and protein compared to tissue samples from matching normal patients. The outcomes of the IHC staining study were comparable to those of the bioinformatics analysis discussed above. Additionally, there were substantial predictive values for LUAD patients for ORC1 and ORC6. Furthermore, through accelerating DNA replication, cellular senescence, and metabolic processes, the ORC worked in concert to promote the development of LUAD.

For LUAD patients, the ORC, particularly ORC1/6, had significant prognostic and expression values.

Reference: onlinelibrary.wiley.com/doi/10.1002/cam4.5238

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