High expression of NME1 correlates with progression and poor prognosis in patients of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies that results from genes regulation via different pathways. NME/NM23 nucleoside diphosphate kinase 1 (NME1) is generally regarded as a metastasis suppressor, but its function in HCC is largely unknown. In our study, we explored the role of NME1 in HCC. By analyzing the gene expression omnibus (GEO) database, we discovered that NME1 was more highly expressed in HCC tumor tissues than non-HCC liver tissues (P < 0.001), and NME1 was significantly up-regulated in HCC tumor tissues than in adjacent normal tissues (P < 0.001). Then, validated by the enrolled HCC patients and The Cancer Genome Atlas (TCGA) database, NME1 was upregulated in HCC tumor tissues compared with matched adjacent normal tissue (P < 0.05). Besides, NME1 was down-regulated in Stage III/IV HCC patients than Stage I/II HCC patients (P = 0.009). Moreover, Kaplan-Meier analysis showed that HCC patients with high NME1 expression had poor overall survival (P = 0.004) and higher recurrence rate (P < 0.001). Our data revealed that NME1 was a special oncogene, and its expression was significantly associated with the progression and prognosis of HCC. NME1 may be a novel molecular biomarker for the targeted therapy and prognosis of HCC.

Keywords: NME1; hepatocellular carcinoma; prognosis.

Figure 1

The NME1 expression in human expression profiling array. A. GSE10143, hepatitis/cirrhotic liver tissues (n = 307) vs HCC tumor tissues (n = 80). B. GSE62232, normal liver tissues (n = 10) vs HCC tumor tissues (n = 81). C. GSE36376, adjacent normal tissues (n = 193) vs HCC tumor tissues (n = 240). D. GSE45436, adjacent normal tissues (n = 39) vs HCC tumor tissues (n = 95). Data are shown as mean (SE). ***P < 0.001.

Figure 2

Expression of NME1 were verified by real-time qPCR in enrolled HCC patients. A. Paired adjacent normal tissues (n = 72) vs HCC tumor tissues (n = 72); B. NME1 expression in HCC tissues at I/II (n = 51) and III/IV (n = 21) clinical stages. Results are shown as mean (SE). *P < 0.05, **P < 0.01.

Figure 3

The expression and prognostic value of NME1 were explored by RNA-seq in TCGA database. A. Matched adjacent normal tissues (n = 59) vs HCC tumor tissues (n = 59); B. The correlation between NME1 expression and serum AFP level (n = 377); C and D. Kaplan-Meier curves and estimates of overall survival and recurrence in patients with high or low NME1 expression, p values are calculated based on the log-rank test, ***P < 0.001.