Chromobox homolog 2 protein: A novel biomarker for predicting prognosis and Taxol sensitivity in patients with breast cancer

Abstract

Polycomb group (PcG) complexes modify histones to silence tumor suppressor genes, which exhibit an important function in tumorigenesis and progression. The chromobox (Cbx) protein family is a critical component of PcG-mediated repression. Cbx2, a member of the Cbx protein family, is hypothesized to exhibit a vital role in breast cancer. In the present study, immunohistochemical analysis using tissue microarrays was performed to determine the levels of Cbx2 protein expression in breast cancer. The association between Cbx2 expression and the clinical features and prognosis of 455 breast cancer patients was analyzed. In addition, the efficacy of Taxol was evaluated by comparing the survival of patients with high or low Cbx2 expression. The results revealed that Cbx2 expression was higher in cancer tissues compared with adjacent normal tissues. Furthermore, high Cbx2 expression was significantly associated with large tumor size, lymph node metastasis, high TNM stage and positive human epidermal growth factor receptor-2 (HER-2) status. Patients with high Cbx2 expression also exhibited a shorter mean overall survival (OS) time (74.37 months) compared with patients with low Cbx2 expression (77.37 months). Univariate analysis indicated that high Cbx2 expression increased the risk of mortality by 1.826-fold compared with low Cbx2 expression [hazard ratio (HR), 1.826; 95% confidence interval (CI), 1.069–3.116; P=0.027]. Among patients with high Cbx2 expression, the mean OS time of individuals treated with Taxol (71.01 months) was lower compared with patients that had not received Taxol treatment (78.43 months; log-rank test statistic, 13.03; P<0.001). However, no significant difference in OS time was identified in the low expression group. The results of the current study revealed that Cbx2 may present a novel biomarker for predicting the prognosis of breast cancer patients. Cbx2 may also represent a potential target for treatment due to its important function in Taxol treatment responses.

CBX2 is a functional target of miRNA let‐7a and acts as a tumor promoter in osteosarcoma

“…In addition, PRC1 promotes cancer cell proliferation through regulating the PcG activity in cancer. Recent study has revealed that CBX2 was significantly upregulated in breast cancer and prostate cancer and may serve as a prognostic biomarker . Consistent with this previous study, our study confirmed the dramatically upregulated CBX2 in osteosarcoma and high CBX2 expression was correlated with metastasis, recurrence, and chemotherapy response, as well as unfavorable prognosis in patients with osteosarcoma.…”

“…J, relationship between let-7a expression and CBX2 expression in human osteosarcoma tissues was analyzed (r=−0.475, P = 0.0014) significantly upregulated in breast cancer and prostate cancer and may serve as a prognostic biomarker. [8][9][10] Consistent with this previous study, our study confirmed the dramatically upregulated CBX2 in osteosarcoma and high CBX2 expression was correlated with metastasis, recurrence, and chemotherapy response, as well as unfavorable prognosis in patients with osteosarcoma. Given that osteosarcoma and soft tissue sarcomas might share a similar pathogenesis and etiology, 25 as well as the lack of large cohort of osteosarcoma expression profile, we analyzed the correlation of CBX2 with sarcoma patient survival to further confirm our finding in osteosarcoma with relative large cohort in TCGA dataset.…”

“…The chromobox (CBX2) family, a component of PRC1, is comprised of CBX2/4/6/7/8 . Recent studies have revealed that CBX2 is overexpressed in several cancer type and plays a critical role in tumorigenesis and progression . However, the expression pattern and functional role of CBX2 in osteosarcoma and its regulatory mechanisms are still unknown.…”

A novel approach to modeling transcriptional heterogeneity identifies the oncogene candidate CBX2 in invasive breast carcinoma

“…A significant reduction in 5-year survival in tumors that overexpressed CBX2 versus those that did not was observed (q = 0.03, log-rank test, Figure 6). This result in consistent with a report that found that high levels of CBX2 protein expression in breast tumors was associated with an increased risk of mortality 14 .…”

“…For example, the gene CBX2 was recently shown to be highly-expressed in both androgen-independent, late stage prostate cancers (PrCa) and distant PrCa metastases 12 . CBX2 is a member of the polycomb repressive complex (PRC), and expression of this gene and its protein product is negatively associated with breast cancer survival 13,14 . In addition, NELL2 is a neural cell growth factor whose expression is positively regulated by estrogen and that promotes invasion of breast cancer cells 15,16 .…”