Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 28:12:972550.
doi: 10.3389/fonc.2022.972550. eCollection 2022.

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

Yang Yang  1 , Jinyan Yuan  1 , Zhenzhong Liu  1 , Wenwen Cao  2 , Pei Liu  3
Affiliations

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

Yang Yang et al. Front Oncol. .

Abstract

Background: Cholangiocarcinoma (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 methods: In 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.

Results: HJURP 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.

Conclusions: HJURP 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.

Keywords: CCA subsets; HJURP; biomarker; cholangiocarcinoma; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The expression of HJURP in CCA. (A) The fragments per kilobase of exon model per million mapped fragments (FPKMs) of HJURP in CCAs and para-tumor tissues in TCGA database. (B) The FPKMs of HJURP in iCCAs, ehCCAs, and their para-tumor tissues in the database with GSE33327 and GSE132305. (C) HJURP expression in CCAs was detected with IHC, dividing the patients into low and high HJURP expressions. (D) The IHC scores of pCCAs and dCCAs were higher than iCCAs. * represents P < 0.05, and n.s. represents not significant. In A, B, and D, statistical significance was analyzed by t test.
Figure 2
Figure 2
The prognostic significance of HJURP in iCCA, pCCA, and dCCA. The patients with iCCA (A), pCCA (B), and dCCA (C) were divided into low- or high-HJURP subgroups, and the statistical significance between subgroups was analyzed with the log-rank test.
Figure 3
Figure 3
The prognostic significance of clinicopathological factors in iCCA. In iCCA, the prognosis-relevant factors included histological grade (A), T stage (B), N stage (C), and TNM stage (D). The statistical significance between subgroups was analyzed with the log-rank test.
Figure 4
Figure 4
The prognostic significance of clinicopathological factors in pCCA. In pCCA, the prognosis-relevant factors included tumor size (A), T stage (B), and TNM stage (C). The statistical significance between subgroups was analyzed with the log-rank test.
Figure 5
Figure 5
The prognostic significance of clinicopathological factors in dCCA. In dCCA, the prognosis-relevant factors included TNM stage. The statistical significance between subgroups was analyzed with the log-rank test.
See this image and copyright information in PMC

References

    1. Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma - evolving concepts and therapeutic strategies. Nat Rev Clin Oncol (2018) 15(2):95–111. doi: 10.1038/nrclinonc.2017.157 - DOI - PMC - PubMed
    1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet (2014) 383(9935):2168–79. doi: 10.1016/S0140-6736(13)61903-0 - DOI - PMC - PubMed
    1. Chen T, Li K, Liu Z, Liu J, Wang Y, Sun R, et al. . WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1alpha accumulation in myc-dependent and independent pathways. Mol Ther (2021) 29(6):2134–50. doi: 10.1016/j.ymthe.2021.02.017 - DOI - PMC - PubMed
    1. Li Z, Liu J, Chen T, Sun R, Liu Z, Qiu B, et al. . HMGA1-TRIP13 axis promotes stemness and epithelial mesenchymal transition of perihilar cholangiocarcinoma in a positive feedback loop dependent on c-myc. J Exp Clin Cancer Res (2021) 40(1):86. doi: 10.1186/s13046-021-01890-1 - DOI - PMC - PubMed
    1. Montal R, Sia D, Montironi C, Leow WQ, Esteban-Fabro R, Pinyol R, et al. . Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J Hepatol (2020) 73(2):315–27. doi: 10.1016/j.jhep.2020.03.008 - DOI - PMC - PubMed

LinkOut - more resources