Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer – A Comprehensive Bioinformatics Analysis

Abstract

Objective We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC). Methods Kaplan–Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan–Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC. Results ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration. Conclusion ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

Identification of a cuproptosis related chromatin regulators signature for lung adenocarcinoma

“…L3MBTL3, a member of the putative polycomb group (PcG) protein family, is thought to be associated with cancer risk [47]. Meanwhile, we discovered a strong connection between the Origin Recognition Complex (ORC) gene family and various cancer types [48,49]. However, researchers have paid little attention to ORC2 and its role in cancer progression and metastasis.…”

Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression

“…ORC6 is a cofactor in the mismatch repair (MMR) complex that promotes efficient mismatch repair (8). In recent years, research has identified a correlation between elevated ORC6 expression and adverse prognostic outcomes in patients with colorectal cancer (9), renal clear cell carcinoma (10), gastric adenocarcinoma (11), and breast cancer (12). Current research on ORC6 in tumors is restricted to specific types of human cancers.…”