A Seven-Gene Signature to Predict Prognosis of Patients With Hepatocellular Carcinoma

Abstract

Purpose: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and has a poor prognosis. Gene-based prognostic models have been reported to predict the overall survival of patients with HCC. Unfortunately, most of the genes used in earlier prognostic models lack prospective validation and, thus, cannot be used in clinical practice.Methods: Candidate genes were selected from GEPIA (Gene Expression Profiling Interactive Analysis), and their associations with patients’ survival were confirmed by RT-PCR using cDNA tissue microarrays established from patients with HCC after radical resection. A multivariate Cox proportion model was used to calculate the coefficient of corresponding gene. The expression of seven genes of interest (MKI67, AR, PLG, DNASE1L3, PTTG1, PPP1R1A, and TTR) with two reference genes was defined to calculate a risk score which determined groups of different risks.Results: Our risk scoring efficiently classified patients (n = 129) with HCC into a low-, intermediate-, and high-risk group. The three groups showed meaningful distinction of 3-year overall survival rate, i.e., 88.9, 74.5, and 20.6% for the low-, intermediate-, and high-risk group, respectively. The prognostic prediction model of risk scores was subsequently verified using an independent prospective cohort (n = 77) and showed high accuracy.Conclusion: Our seven-gene signature model performed excellent long-term prediction power and provided crucially guiding therapy for patients who are not a candidate for surgery.

Hepatocellular carcinoma subtypes based on metabolic pathways reveals potential therapeutic targets

“…One study showed that epithelial cell adhesion molecules were downregulated by 5-fluorouracil (5FU) in human HCC cell lines (HepG2, Hep3B and HuH-7) and upregulated by cisplatin in the HuH-7 cells, indicating that these molecules are targets of chemoresistance (51) and play an important role in tumor recurrence and progression. Furthermore, the expression levels of APOA2, RPB4, TTR, APOH and some HCC-related genes were significantly different between HCC and control samples (45,(52)(53)(54). These findings are consistent with the roles played by different stromal cells during tumor growth (55).…”

Downregulation of indolethylamine N‐methyltransferase is an early event in the rat hepatocarcinogenesis and is associated with poor prognosis in hepatocellular carcinoma patients

“…Coincidently, previous studies have reported a close relationship between increased expression of ANXA2 , 31 EGLN3 , 32 GAS2L3 , 33 MKI67 , 31 MMP12 , 34 NQO1 35 and PTTG1 36 genes and poor survival in HCC tumors, while variants of PPP1RB gene have been associated with liver steatosis and increased risk of developing liver cancer 37 . Since our comparison revealed INMT as the most downregulated gene (Supplementary Table S5), we analyzed its expression among the 371 cases from the TCGA database.…”

Prognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based on Proteomics

“…PLG encodes a serine protease called plasminogen, which is located on the cell surfaces and is essential for the degradation of extracellular matrices, cell migration, inflammation, oncogenesis, and metastasis [30]. PLG was found to be a prognostic protective factor in HCC [31,32] and a potential biomarker for prediction of papillary thyroid carcinoma [33], but there has been no report of it in PDAC. COPS5 (also known as CSN5) is the fifth component of the COP9 signalosome complex and affects a variety of cellular processes [34].…”