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Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma.

ABSTRACT: Identifying novel prognostic biomarkers for hepatocellular carcinoma (HCC) and then, develop an effective individualized treatment strategy remain extremely warranted. The prognostic role of sulfiredoxin-1(SRXN1), an antioxidant enzyme, remains unknown in HCC. This study aimed to explore the prognostic implications of SRXN1 in HCC patients after partial hepatectomy. The expression of SRXN1 in HCC and normal tissue were analyzed using the patients from the public databases and Zhongshan Hospital. The Cox regression, Kaplan-Meier survival analysis, and time-dependent receiver operating characteristic curves were performed to identify the predictive role of SRXN1 expression on HCC patients. A prognostic nomogram based on SRXN1 expression was constructed and validated to further confirm the predictive power of SRXN1 as a prognostic biomarker. Finally, functional enrichment analysis and protein-protein interaction network analysis of SRXN1 and its associated genes were conducted. The results showed that SRXN1 was upregulated in HCC samples compared with the normal liver tissues. Patients with SRXN1 upregulation had shorter survival time. SRXN1 overexpression was significantly correlated with advanced clinicopathological parameters. The prognostic nomogram based on SRXN1 expression was proved to be more accurate than routine staging systems for the prediction of overall survival. Protein-protein interaction network analysis demonstrated the first neighbor genes of SRXN1 mainly participated in response to oxidative stress. In brief, SRXN1 could be a prognostic biomarker for the management of HCC.

SUBMITTER: Rao QW

PROVIDER: S-EPMC7666720 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma.

Rao Qian-Wen QW Zhang Shi-Long SL Guo Meng-Zhou MZ Yuan Fei-Fei FF Sun Jia-Lei JL Qi Feng F Wang Li-Shun LS Yang Bi-Wei BW Xia Jing-Lin JL Xia Jing-Lin JL

Cancer medicine 20200921 22

Identifying novel prognostic biomarkers for hepatocellular carcinoma (HCC) and then, develop an effective individualized treatment strategy remain extremely warranted. The prognostic role of sulfiredoxin-1(SRXN1), an antioxidant enzyme, remains unknown in HCC. This study aimed to explore the prognostic implications of SRXN1 in HCC patients after partial hepatectomy. The expression of SRXN1 in HCC and normal tissue were analyzed using the patients from the public databases and Zhongshan Hospital. ...[more]

PMID: 32955798

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Project description:BackgroundDeoxycytidine kinase (DCK), an enzyme in the nucleoside biosynthetic pathway, can affect the development of immune cells. However, the relationships between the expression of DCK, patient prognosis, and tumor-infiltrating immune cells (TIICs) in hepatocellular carcinoma (HCC) are still unclear.MethodsThe expression of DCK in HCC was analyzed through the Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The impact of DCK on clinical prognosis was investigated via the Kaplan-Meier plotter and verified in the Gene Expression Profiling Interactive Analysis (GEPIA) databases. The interrelationships between DCK expression and TIICs in HCC were analyzed by the TIMER database. Additionally, the relationship between DCK expression and immune cell gene markers was calculated through TIMER and GEPIA databases.ResultsCompared with the adjacent normal tissues, high expression of DCK was observed in HCC tissues. Also, the higher expression of DCK was correlated to poorer prognosis in HCC patients, and it was associated with decreased survival in those with early stage and grade. Moreover, DCK expression was positively correlated with TIICs, including CD4+ and CD8+ T cells, B cells, monocytes, tumor-associated macrophages (TAMs), M1 and M2 macrophages, neutrophils, natural killer cells, and dendritic cells. Specifically, DCK expression levels were significantly associated with diverse immune gene marker sets, including those of Tregs and exhausted T cells.ConclusionThese findings suggest that DCK expression is correlated with patient outcomes and tumor infiltration cell levels in HCC patients. Additionally, the increased level of DCK was associated with marker genes of Tregs and exhaustion-related inhibitory receptors, suggesting the potential role of DCK in immunosuppression and immune escape. These findings suggest that DCK can function as a potential novel prognostic biomarker and reflect the immune infiltration status in HCC patients.

Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown.MethodsTCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro.ResultsMRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro.ConclusionsWe demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.

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Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma.

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Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma.

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