ORC6 drives the malignant progression of cervical squamous intraepithelial lesions and serves as a biomarker for high-grade dysplasia.

BACKGROUND

Origin Recognition Complex Subunit 6 (ORC6) is essential for DNA replication initiation. However, its dynamic expression patterns and potential biological functions during the progression of cervical lesions remain unclear.

METHODS

We analyzed the differential expression of ORC6 in cervical cancer and normal tissues using an integrated TCGA-GTEx-CESC dataset and explored its potential regulatory mechanisms via GO/KEGG, GSEA, and CIBERSORT immune infiltration analyses. Furthermore, a total of 163 clinical tissue specimens (including CIN I, CIN II, CIN III, and invasive cervical carcinoma) were examined by immunohistochemistry (IHC) to evaluate ORC6 protein expression and its association with pathological grade and clinicopathological characteristics.

RESULTS

Bioinformatics analysis revealed that ORC6 was significantly upregulated in cervical cancer (P < 0.001) and was associated with transcriptional programs related to E2F targets, DNA replication, and the G2/M checkpoint. Immune infiltration analysis showed that elevated ORC6 expression was associated with a distinct immune infiltration pattern, characterized by increased M0 macrophages and reduced activated NK cells, resting NK cells, and CD8+ T cells. IHC analysis further demonstrated that ORC6 expression was significantly increased in cervical lesions and invasive carcinoma compared with normal cervical tissues (P < 0.001). Notably, ORC6 expression was significantly higher in the CIN II-III group than in the CIN I group (P < 0.01). In contrast, ORC6 expression was not significantly associated with tumor differentiation, lymph node metastasis, vascular invasion, perineural invasion, or overall survival (all P > 0.05).

CONCLUSION

ORC6 is closely associated with the progression of HPV-related cervical lesions, particularly the transition from CIN I to CIN II-III. ORC6 may serve as a potential auxiliary biomarker for the identification and early stratification of high-grade squamous intraepithelial lesions (HSIL).