Dataset Information

High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.

ABSTRACT: Rap2A is overexpressed in a multitude of human cancers and plays an important role in cytoskeleton rearrangement, arteriogenesis and cell migration. However, its role and function in hepatocellular carcinoma (HCC) has not yet been explored. Here, we aimed to investigate the expression of Rap2A in HCC and the relationship between Rap2A and clinicopathologic features of patients. Western blot and quantitative real-time PCR (qRT-PCR) showed that Rap2A was remarkably upregulated in HCC tissues compared to adjacent normal liver tissues. Immunohistochemistry (IHC) showed that Rap2A was mainly localized in the cytoplasm rather than nuclei in HCC tissues. Overexpression of Rap2A was significantly correlated with tumor size (P=0.019), metastasis (P=0.002), pathological differentiation (P=0.028) and vascular invasion (P=0.017) in HCC. Kaplan-Meier analysis demonstrated that HCC patients with high Rap2A expression had shorter overall survival time than those with low Rap2A expression (P=0.011). Furthermore, High level of Rap2A was a risk factor for HCC patients according to Cox's proportional hazard regression (P=0.026). In summary, our results suggest that high expression of Rap2A is involved in HCC progression and might be a novel prognostic indicator for patients.

SUBMITTER: Zheng X

PROVIDER: S-EPMC6965967 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.

Zheng Xuqing X Zhao Wenxiu W Ji Piyou P Zhang Kang K Jin Jianbin J Feng Min M Wang Fei F Zheng Sen S Wang Xiaomin X

International journal of clinical and experimental pathology 20170901 9

Rap2A is overexpressed in a multitude of human cancers and plays an important role in cytoskeleton rearrangement, arteriogenesis and cell migration. However, its role and function in hepatocellular carcinoma (HCC) has not yet been explored. Here, we aimed to investigate the expression of Rap2A in HCC and the relationship between Rap2A and clinicopathologic features of patients. Western blot and quantitative real-time PCR (qRT-PCR) showed that Rap2A was remarkably upregulated in HCC tissues compa ...[more]

PMID: 31966838

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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 Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.

Publications

High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.

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