Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage; however, the effect of systemic therapy on advanced HCC remains undetermined. Therefore, new treatment targets must be identified. We analyzed Gene Expression Omnibus datasets from two HCC patient cohorts and found that NT5DC2 was associated with vascular invasion and poor survival. In two hepatoma cell lines, NT5DC2 overexpression promoted HCC cell proliferation and clone formation in vitro and promoted tumor growth in vivo. Coimmunoprecipitation assays and liquid chromatography with tandem mass spectrometry analysis revealed that NT5DC2 bound directly to epidermal growth factor receptor (EGFR). NT5DC2 upregulated EGFR expression by downregulating EGFR ubiquitination and preventing its degradation via the ubiquitin-proteasome pathway but did not upregulate its transcription. EGFR upregulation activated downstream signal transduction, which played a critical role in the protumor effects of NT5DC2. Erlotinib, a small-molecule inhibitor of EGFR, blocked the effect of NT5DC2 in promoting HCC cell proliferation. In a cohort of 79 patients who underwent curative resection for HCC, NT5DC2 expression in the tumors was associated with larger tumors and microvascular invasion. NT5DC2 expression was also independently associated with recurrence-free survival. The present study demonstrated for the first time that NT5DC2 promotes tumor cell proliferation in HCC and may serve as a potential molecular target for treating HCC. EGFR blockage could be used to treat selected patients with NT5DC2 upregulation.
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PMID:NT5DC2 promotes tumor cell proliferation by stabilizing EGFR in hepatocellular carcinoma. 3238 41

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.
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PMID:NT5DC2 is a novel prognostic marker in human hepatocellular carcinoma. 3286 3