Pan-cancer analysis based on epigenetic modification explains the value of HJURP in the tumor microenvironment

Abstract

To analyze the expression levels, prognostic value and immune infiltration association of Holliday junction protein (HJURP) as well as its feasibility as a pan-cancer biomarker for different cancers. The Protter online tool was utilized to obtain the localization of HJURP, then the methylation of HJURP in tumors were further explored. Thereafter, the mRNA data and clinical characteristics of 33 tumor types from TCGA database were obtained to investigate the expression and prognostic relationship of HJURP in different tumor types. Finally, the composition pattern and immune infiltration of HJURP in different tumors were detected in Tumor Immune Estimation Resource. HJURP was abnormally expressed in most of the cancer types and subtypes in TCGA database. Also, it was associated with poor prognosis of different cohorts. At the same time, the results also showed that HJURP was related to tumor immune evasion through different mechanisms, including T cell rejection and methylation in different cancer types. Besides, the methylation of HJURP was inversely proportional to mRNA expression levels, which mediated the dysfunctional phenotypes of T cells and poor prognosis of different cancer types. Alternatively, our results indicated that HJURP expression was associated with immune cell infiltration in a variety of cancers. HJURP may serve as an oncogenic molecule, and its expression and immune infiltration characteristics can be used as a biomarker for cancer detection, prognosis, treatment design and follow-up.

Emerging role of HJURP as a therapeutic target in cancers

“…For example, in U2OS cells, serous ovarian cancer cells, and t(4;14)-positive multiple myeloma cells, HJURP has been observed to localize in the nucleus [8,9,12,72]. HJURP has been further found to co-localize with ER and microtubules in U2OS cells [15]; however, in various cancer cells, including HCC, and prostate and breast cancers, HJURP is mainly expressed in the cytoplasm [34,48,53,54]. HJURP has been located in the cytoplasm and/or cell membrane in CRC [41], while in gliomas HJURP immunoreactivity has been observed in both the nucleus and cytoplasm, increasing with the grade of gliomas [64].…”

“…Abnormal upregulation of HJURP has been demonstrated in various human cancers based on public genomics databases and independent patient cohorts. Two pan-cancer analyses were performed to determine the relationship between HJURP and cancer [14,15]. Specifically, these studies showed that HJURP expression is upregulated in most human cancers.…”

“…HJURP expression increases during cell cycle progression. G2 is the phase with the highest expression, suggesting a role for HJURP in cell cycle regulation [15]. Furthermore, HJURP has been shown to mediate tumor immune evasion and interacts with immune infiltration and T cell immune exclusion, thus promoting cancer progression and metastasis [15].…”