Abstract:Background: Hepatocellular carcinoma is the most common type of primary liver cancer, and it is associated with poor prognosis. It often fails to respond to immunotherapy, highlighting the need to identify genes that are associated with the tumor microenvironment and may be good therapeutic targets. We and others have shown that the Holliday cross-recognition protein HJURP can promote the proliferation, migration, and invasion by hepatocellular carcinoma cells, and that HJURP overexpression is associated with … Show more
“…HJURP can participate in various cell proliferation-related pathways and promote the proliferation of tumor cells, such as HCC. This is consistent with the fact that HJURP requires CENPA to bind to centrioles during telolobe/early G1 phase, which ensures normal chromosome segregation during mitosis 16 . However, there is no sufficient and effective evidence for the pathogenesis of HJURP in a variety of cancers, and it remains unclear about whether HJURP plays a role in TME, cell cycle progression, tumor treatment and prognosis through a common molecular mechanism in the context of immunocytological action.…”
Section: Introductionsupporting
confidence: 86%
“…GO enrichment analysis of HJURP and these gene functional partners revealed that they have immune-related functions. Clustering dendrogram of the top-ranked GO biological processes (GO-BP) showing major pathways such as cellular detection biotic interferon-gamma, neuron death oxidative stress, immune assembly phagocytosis bioprocesses, gland migration morphogenesis duct and interleukin-1 cysteine-type production endopeptidase 16 . Figure 2 HJURP showed changes in protein expression levels associated with interval progression in G1, S, and G2 phasesa ( A ).…”
Section: Resultsmentioning
confidence: 99%
“…Zhang et al suggested that HJURP is a potential independent prognostic marker for clear cell renal cell carcinoma (ccRCC), which plays an important role in the tumor microenvironment by regulating immune cell infiltration 33 . Luo et al believed that HJURP is related to tumor-infiltrating immune cells, immune checkpoints and immunosuppression in HCC, and HJURP-related genes involved in immune response may help predict the prognosis of patients 16 . Chen et al also found significant associations between HJURP and several tumor-infiltrating immune cells, immunomodulators, and immune subtypes in lung adenocarcinoma (LUAD) patients 34 .…”
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.
“…HJURP can participate in various cell proliferation-related pathways and promote the proliferation of tumor cells, such as HCC. This is consistent with the fact that HJURP requires CENPA to bind to centrioles during telolobe/early G1 phase, which ensures normal chromosome segregation during mitosis 16 . However, there is no sufficient and effective evidence for the pathogenesis of HJURP in a variety of cancers, and it remains unclear about whether HJURP plays a role in TME, cell cycle progression, tumor treatment and prognosis through a common molecular mechanism in the context of immunocytological action.…”
Section: Introductionsupporting
confidence: 86%
“…GO enrichment analysis of HJURP and these gene functional partners revealed that they have immune-related functions. Clustering dendrogram of the top-ranked GO biological processes (GO-BP) showing major pathways such as cellular detection biotic interferon-gamma, neuron death oxidative stress, immune assembly phagocytosis bioprocesses, gland migration morphogenesis duct and interleukin-1 cysteine-type production endopeptidase 16 . Figure 2 HJURP showed changes in protein expression levels associated with interval progression in G1, S, and G2 phasesa ( A ).…”
Section: Resultsmentioning
confidence: 99%
“…Zhang et al suggested that HJURP is a potential independent prognostic marker for clear cell renal cell carcinoma (ccRCC), which plays an important role in the tumor microenvironment by regulating immune cell infiltration 33 . Luo et al believed that HJURP is related to tumor-infiltrating immune cells, immune checkpoints and immunosuppression in HCC, and HJURP-related genes involved in immune response may help predict the prognosis of patients 16 . Chen et al also found significant associations between HJURP and several tumor-infiltrating immune cells, immunomodulators, and immune subtypes in lung adenocarcinoma (LUAD) patients 34 .…”
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.
“…We used the principal components analysis (PCA) (orthogonal rotation) method in the "IOBR" package 35 to construct a scoring system to evaluate the levels of 44 collagen molecules in SKCM patients and named it Col_Score. The Col_Score formula is Col_Score = ∑(PC1+PC2).…”
The incidence of cutaneous melanoma continues to rise rapidly and has an extremely poor prognosis. Immunotherapy strategies are the most effective approach for patients who have developed metastases, but not all cases have been successful due to the complex and variable mechanisms of melanoma response to immune checkpoint inhibition. Methods: We synthesized collagen-coding gene expression data (second-generation and single-cell sequencing) from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as Metascape database, Gene Set Cancer Analysis (GSCA) database, and Cytoscape software, etc., to investigate the biological mechanisms that may be related with collagens. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of Nidogen-2 (NID2). Results: Melanoma patients can be divided into two collagen clusters. Patients with high collagen levels (C1) had a shorter survival than those with low collagen levels (C2) and were less likely to benefit from immunotherapy. We demonstrated that NID2 is a potential key factor in the collagen phenotype, is involved in fibroblast activation in melanoma, and forms a barrier to limit the proximity of CD8+ T cells to tumor cells.
Conclusion:We clarified the adverse effects of collagen on melanoma patients and identified NID2 as a potential therapeutic target.
“…Aberrant expression of chromatin regulators (CRs) has a major impact on immune responses. For example, HJURP has been associated with immune cell infiltration and immune checkpoint expression in hepatocellular carcinoma and clear cell renal cell carcinoma (8)(9)(10). HMGB3 was a member of a family of chromatin-binding proteins that can modify DNA structure to facilitate transcription factor binding (11,12).…”
BackgroundDysregulation of chromatin regulators (CRs) can perturb the tumor immune microenvironment, but the underlying mechanism remains unclear. We focused on uterine corpus endometrial carcinoma (UCEC) and used gene expression data from TCGA-UCEC to investigate this mechanism.MethodsWe used weighted gene co-expression network analysis (WGCNA) and consensus clustering algorithm to classify UCEC patients into Cluster_L and Cluster_H. TME-associated CRs were identified using WGCNA and differential gene expression analysis. A CR risk score (CRRS) was constructed using univariate Cox and LASSO-Cox regression analyses. A nomogram was developed based on CRRS and clinicopathologic factors to predict patients' prognosis.ResultsLower CRRS was associated with lower grade, more benign molecular subtypes, and improved survival. Patients with low CRRS showed abundant immune infiltration, a higher mutation burden, fewer CNVs, and better response to immunotherapy. Moreover, low CRRS patients were more sensitive to 24 chemotherapeutic agents.ConclusionA comprehensive assessment of CRRS could identify immune activation and improve the efficacy of UCEC treatments.
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