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High expression of B7?H2 or B7?H3 is associated with poor prognosis in hepatocellular carcinoma.

ABSTRACT: B7 family members have been associated with the signaling transduction pathways underlying tumor immune evasion in hepatocellular carcinoma. In the present study, associations between the clinical characteristics of patients with hepatocellular carcinoma (HCC) and the expression of B7?H2 and B7?H3 were analyzed. A total of 63 formalin?fixed and paraffin?embedded HCC tissues were collected to be used as a tissue microarray. Following this, the association between B7?H2/B7?H3 and the prognosis of patients with HCC was analyzed using Pearson's ?2 test, the Kaplan?Meier method and receiver operating characteristic curve analysis. The results demonstrated that the expression of B7?H2 was significantly associated with recurrence (within 1 year) in patients with HCC (P<0.01), and that the expression of B7?H3 was associated with recurrence (within 1 year), metastasis and 2?year overall survival rate in patients with HCC (P<0.01, P=0.036 and P=0.016, respectively). In addition, the combined expression of B7?H2 and B7?H3 was associated with prognostic factors, including recurrence (within 1 year) and survival rate (within 2 years), in patients with HCC. In particular, an increased area under the curve was achieved when the combined expression of B7?H2 and B7?H3 was considered, compared with that for ??fetoprotein. Taken together, these results indicated that B7?H2? and/or B7?H3?positive expression indicates a poor clinical outcome for patients, and the combination of B7?H2 and B7?H3 may be a preferential prognostic biomarker in patients with HCC.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC6472081 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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High expression of B7‑H2 or B7‑H3 is associated with poor prognosis in hepatocellular carcinoma.

Zheng Youshi Y Liao Naishun N Wu Yuan Y Gao Ju J Li Zhenli Z Liu Wenwen W Wang Yingchao Y Li Ming M Li Xiaolou X Chen Li L Zhang Wenmin W Zhao Bixing B

Molecular medicine reports 20190322 5

B7 family members have been associated with the signaling transduction pathways underlying tumor immune evasion in hepatocellular carcinoma. In the present study, associations between the clinical characteristics of patients with hepatocellular carcinoma (HCC) and the expression of B7‑H2 and B7‑H3 were analyzed. A total of 63 formalin‑fixed and paraffin‑embedded HCC tissues were collected to be used as a tissue microarray. Following this, the association between B7‑H2/B7‑H3 and the prognosis of ...[more]

PMID: 30942404

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Project description:Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-? (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase II?. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319×10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40×10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

Project description:BackgroundDNA methylation patterns have been found to be distinct between tumor and normal patients. However, the effect of DNA demethylation enzymes, ten eleven translocation (TET) proteins, has not been comprehensively characterized in liver cancer. In this research, we sought to unravel the linkage of TET proteins with prognosis, immune characteristics and biological pathways in hepatocellular carcinoma (HCC).Materials and methodsFour independent datasets with gene expression data and clinical data of HCC samples were downloaded from public databases. CIBERSORT, single sample Gene Set Enrichment Analysis (ssGSEA), MCP-counter, and TIMER were implemented to evaluate immune cell infiltration. limma was employed to screen differentially expressed genes (DEGs) between two groups. The demethylation-related risk model was established by using univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO), and stepwise Akaike information criterion (stepAIC).ResultsTET1 was significantly higher expressed in tumor samples than that in normal samples. HCC patients with advanced stages (III+IV) and grades (G3+G4) had higher TET1 expression compared to early stages (I+II) and grades (G1+G2). HCC samples with high TET1 expression had worse prognosis than that with low expression. High and low TET1 expression groups had distinct immune cell infiltration and response to immunotherapy and chemotherapy. We identified 90 DEGs related to DNA demethylation in high vs. low TET1 expression groups. Furthermore, we established a risk model based on 90 DEGs containing seven key prognostic genes (SERPINH1, CDC20, HACD2, SPHK1, UGT2B15, SLC1A5, and CYP2C9) with effectiveness and robustness in predicting HCC prognosis.ConclusionsOur study suggested TET1 as a potential indicator in HCC progression. TET1 was closely involved in immune infiltration and activation of oncogenic pathways. The DNA demethylation-related risk model was potential to be applied for predicting HCC prognosis in clinics.

Dataset Information

High expression of B7?H2 or B7?H3 is associated with poor prognosis in hepatocellular carcinoma.

Publications

High expression of B7‑H2 or B7‑H3 is associated with poor prognosis in hepatocellular carcinoma.

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