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NT5DC2 is a novel prognostic marker in human hepatocellular carcinoma.

ABSTRACT: Reliable biomarkers for the prognosis of hepatocellular carcinoma (HCC) are rare, and novel biomarkers are required for the appropriate management of HCC. 5'-Nucleotidase domain containing 2 (NT5DC2) acts as an oncogene in various tumors, but its functions as a biomarker have not been confirmed. Therefore, the present study aimed to resolve these functions by analyzing the prognostic value of NT5DC2 in patients with HCC. A tissue microarray (TMA) was prepared and NT5DC2 expression was measured via IHC staining in TMA dots. The liver cancer (LIHC) cohort in The Cancer Genome Atlas (TCGA) was enrolled as a secondary cohort. Kaplan-Meier survival analyses and Cox regression models were used for assessment of the prognostic value of NT5DC2. Gene set enrichment analysis (GSEA) was performed in TCGA LIHC cohort. A total of 134 patients with HCC were retrospectively enrolled in the Peking Union Medical College Hospital cohort and clinical data were collected. A total of 359 patients with HCC in TCGA were enrolled as TCGA cohort. NT5DC2 was used as an indicator of overall survival (OS) and relapse-free survival (RFS) in multiple cohorts. In the multivariate Cox regression model, NT5DC2 upregulation was an independent prognostic factor of OS in both cohorts. GSEA indicated the enrichment of a series of survival- and metastasis-related gene-sets, such as LEE_LIVER_CANCER_SURVIVAL_UP and LIAO_METASTASIS. Collectively, it was suggested that NT5DC2 upregulation was associated with poor OS and RFS in HCC, and was a potential predictive marker for HCC stratification.

SUBMITTER: Chen J

PROVIDER: S-EPMC7436888 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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NT5DC2 is a novel prognostic marker in human hepatocellular carcinoma.

Chen Jiemin J Cao Jianzhong J Wang Penghui P He Xiaodong X

Oncology letters 20200729 4

Reliable biomarkers for the prognosis of hepatocellular carcinoma (HCC) are rare, and novel biomarkers are required for the appropriate management of HCC. 5'-Nucleotidase domain containing 2 (NT5DC2) acts as an oncogene in various tumors, but its functions as a biomarker have not been confirmed. Therefore, the present study aimed to resolve these functions by analyzing the prognostic value of NT5DC2 in patients with HCC. A tissue microarray (TMA) was prepared and NT5DC2 expr ...[more]

PMID: 32863903

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Project description:Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine-cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein-protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

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NT5DC2 is a novel prognostic marker in human hepatocellular carcinoma.

Publications

<i>NT5DC2</i> is a novel prognostic marker in human hepatocellular carcinoma.

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