Evaluation of the prognostic value of paraoxonase 1 in the recurrence and metastasis of hepatocellular carcinoma and establishment of a liver-specific predictive model of survival

Abstract

BackgroundHepatocellular carcinoma is a malignant tumor with a highly invasive and metastatic phenotype, and the detection of potential indicators associated with its recurrence and metastasis after surgical resection is critical for patient survival.MethodsTranscriptome data for large cohorts (n = 1432) from multicenter sources were comprehensively analyzed to explore such potential signatures. The prognostic value of the selected indicators was investigated and discussed, and a comparison with conventional clinicopathological features was performed. A survival predictive nomogram for 5-year survival was established with the selected indicator using the Cox proportional hazards regression. To validate the indicator at the protein level, we performed immunohistochemical staining with paraffin-embedded slides of hepatocellular carcinoma samples (n = 67 patients) from our hospital. Finally, a gene set enrichment analysis (GSEA) was performed to detect the underlying biological processes and internal mechanisms.ResultsThe liver-specific protein paraoxonase 1 (PON1) was found to be the most relevant indicator of tumor recurrence, invasiveness, and metastasis in the present study, and the downregulation of PON1 might reveal poor survival for patients with hepatocellular carcinoma. The C-index of the PON1-related nomogram was 0.714, thus indicating a more effective predictive performance than the 7th American Joint Committee on Cancer (AJCC) tumor stage (0.534), AJCC T stage (0.565), or alpha-fetoprotein (0.488). The GSEA revealed that PON1 was associated with several hepatocellular carcinoma-related pathways, including the cell cycle, DNA replication, gap junction and p53 downstream pathways.ConclusionsThe downregulation of paraoxonase 1 may suggest worse outcomes and a higher recurrence rate. Thus, paraoxonase 1 might represent an indicator for predicting the survival of patients with hepatocellular carcinoma.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1707-0) contains supplementary material, which is available to authorized users.

A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma

“…Interestingly, GAST can also expresses in a group of primary human tumors, including neuronal, renal, and myogenic stem cell tumors [ 25 ], which suggest that GAST may play a previously unrecognized role in human CSC. Galanin and GMAP Prepropeptide (GAL) has been demonstrated to activate in human HCC, and it prefers to accumulate in the stromal tissue around the HCC cells [ 26 ]; Somatostatin (SST) is a kind of hormone that can inhibits the release of various secondary hormones; Paraoxonase 1 (PON1) was found to be a highly related predictor of recurrence and metastasis in HCC [ 27 ]; Production and Homeostasis of Lipoprotein(A) (LPA) can be impaired when liver cancer occurs [ 28 ]; and both the downregulation of PON1 [ 27 ] and alcohol dehydrogenase 4 (Class II), Pi polypeptide (ADH4) [ 29 ] can confers poor survival time of HCC. However, the relationship among these genes and CSC or stemness was seldom reported.…”

Diagnostic and Prognostic Characteristics of Circulating Free DNA Methylation Detected by the Electrochemical Method in Malignant Tumors

“…The results showed that the cfDNA adsorption rate is an indicator of possible potential malignant tumor efficacy monitoring and prognosis evaluation. However, its sensitivity and specificity in monitoring efficacy is low, and its recurrence diagnostic efficacy is similar to clinical tumor biomarkers such as CEA and AFP [41,42]. When the sensitivity increases, the specificity is significantly reduced.…”

A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma

“…A growing body of evidence has suggested that PON1 could serve as an important clinical indicator of cancer progression for a number of cancers such as lung cancer and breast cancer (Bobin-Dubigeon et al, 2015;Aldonza et al, 2017). Data in THPA database showed that the expression of PON1 in HCC is significantly higher than that in other tumors, and its down-regulated expression has been implicated to be a poor indicator for survival in patients with HCC (Yu et al, 2018). MAPK7 (mitogen-activated protein kinase 7) encodes extracellular-regulated protein kinase 5 (ERK5).…”