The expression, clinical relevance, and prognostic significance of HJURP in cholangiocarcinoma

Abstract

BackgroundCholangiocarcinoma (CCA) is the malignancy originating from the biliary epithelium, including intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCA. The prognosis of CCA is very poor, and the biomarkers of different CCA subsets should be investigated separately. Holliday junction recognition protein (HJURP) is a key component of the pre-nucleosomal complex, which is responsible for normal mitosis. The ectopic expression of HJURP has been reported in several cancers, but not CCA.Materials and methodsIn our study, we investigated the expression of HJURP in 127 CCA patients which were composed of 32 iCCAs, 71 pCCAs, and 24 dCCAs with immunohistochemistry and divided these patients into subgroups with a low or high expression of HJURP. With chi-square test and univariate and multivariate analyses, we evaluated the clinical relevance and prognostic significance of HJURP in iCCAs, pCCAs, and dCCAs.ResultsHJURP was ectopically upregulated in CCAs compared with the para-tumor tissues based on TCGA and other mRNA-seq databases. A high expression of HJURP was correlated with low overall survival rates of iCCA and pCCA, but not in dCCA. Moreover, HJURP was an independent prognostic biomarker in both iCCA and pCCA. Patients with high HJURP were more likely to suffer CCA-related death after operation.ConclusionsHJURP was an independent prognostic biomarker in both iCCA and pCCA, but not in dCCA. Our results provide more evidence of the molecular features of different CCA subsets and suggest that patients with high HJURP are more high-risk, which can guide more precision follow-up and treatment of CCA.

The Clinical Impact of Death Domain-Associated Protein and Holliday Junction Recognition Protein Expression in Cancer: Unmasking the Driving Forces of Neoplasia

“…The role of HJURP in biliary tract neoplasia was investigated by Yang et al who reported increased HJURP expression in cholangiocarcinoma (CCA) tissue samples compared to non-tumorous ones. Additionally, HJURP overexpression was associated with lower OS in cases of intrahepatic and perihilar CCA but not in patients with distal CCA [52]. Thus, the study highlights the potential role of HJURP as a tumor-promoting factor (Figure 2) and a marker of worse prognosis (Figure 3) in CCAs.…”

Emerging role of HJURP as a therapeutic target in cancers

“…The ectopic expression of HJURP and its prognostic significance in various subtypes of CCA, including intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCA, were investigated [13]. HJURP is highly expressed in all subtypes of CCA and serves as an independent prognostic biomarker in iCCA and pCCA, but not dCCA.…”

“…The HJURP activation requirement for cancer cell immortality was initially identified in 2007 [9,10]. Furthermore, overexpression of HJURP has been observed in various tumor tissues and is associated with poor prognosis, thus making HJURP a potential prognostic cancer biomarker [11][12][13][14]. Given these findings, HJURP could be a key target for cancer treatment.…”

Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer

“…On the other hand, HJURP activates EMT through upregulation of Sphingosine kinase 1 (SPHK1), causing upregulation of vimentin and N-cadherin and downregulation of E-cadherin to promote tumor cell migration, invasion, and metastasis in vivo ( Chen T. et al, 2019 ) ( Figure 4 ). In a recent study employing bioinformatics analysis and immunohistochemistry, Yang et al reported that HJURP was highly expressed in cholangiocarcinoma (CCA) samples ( Yang et al, 2022 ). High expression of HJURP was associated with low overall survival in intrahepatic CCA and perihilar CCA, but not in distal CCA ( Yang et al, 2022 ).…”

“…In a recent study employing bioinformatics analysis and immunohistochemistry, Yang et al reported that HJURP was highly expressed in cholangiocarcinoma (CCA) samples ( Yang et al, 2022 ). High expression of HJURP was associated with low overall survival in intrahepatic CCA and perihilar CCA, but not in distal CCA ( Yang et al, 2022 ). Luo et al reported that high HJURP expression in HCC was associated with tumor-infiltrating immune cells, immune checkpoints, and immunosuppression, verified by gene sequencing analysis ( Luo et al, 2022 ).…”