<p>Identification of a novel DNA repair-related prognostic signature predicting survival of patients with hepatocellular carcinoma</p>

Abstract

Purpose Hepatocellular carcinoma (HCC) is the sixth most lethal neoplasm worldwide. Traditional biomarkers often exploit the relationship between a certain gene and cancer progression, but they cannot predict patient survival or prognosis accurately. We aim to construct a new DNA repair-related gene signature that combines several genes to improve prognosis prediction in HCC. Methods We selected an HCC mRNA sequencing (mRNA-seq) dataset (n=365) from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) was used to explore bioinformatics information and further screen genes. We then built a gene signature based on the Cox proportional hazards regression model. Results GSEA revealed that the hallmark DNA repair gene set was significantly upregulated in the tumor phenotype. A set of seven genes, namely, ADA, FEN1, POLR2G, SAC3D1, SEC61A1, SF3A3 , and UPF3B , were significantly a ssociated with overall survival (OS) and used to form a gene signature. The signature risk score was calculated and used to divide patients into high‐ and low‐risk groups. The high-risk group showed worse prognosis (log-rank test p <0.0001). Univariate and multivariate Cox regression analysis showed that the prognostic performance of this risk score signature was robust in different subgroups based on clinicopathological features, with p -values <0.05 (HR=2.38, 95% CI (confidence interval) =1.355–4.184), indicating that it can serve as an independent prognostic indicator. Conclusion We developed and identified a seven‐gene signature related to the DNA repair process that can predict survival in HCC. It can be used as an effective classification tool and to guide clinical treatment.

Identification of hepatocellular carcinoma prognostic markers based on 10-immune gene signature

“…An immune-related gene expression pattern in liver tissues of patients with early-stage HCC that is associated with risk of HCC development in patients with cirrhosis [24]. A set of seven genes were significantly associated with overall survival (OS) for HCC and used to form a novel DNA repair-related prognostic signature [25]. An immunoscore was constructed, which contained eight immunocyte fraction types, potentially served as a candidate marker to estimate the OS for HBV-related HCC cases [26].…”

Analysis of HBV Genomes Integrated into the Genomes of Human Hepatoma PLC/PRF/5 Cells by HBV Sequence Capture-Based Next-Generation Sequencing

“…The SAC3D1 mRNA is significantly associated with the overall survival of patients with HCC (B Cox value, +0.540; HR (95% CI), 1.717 (0.179–3.0 0); p < 0.0001). Higher expression of SAC3D1 mRNA in HCC is considered a high-risk factor associated with short survival [ 29 ]. SAC3D1 is associated with centrosome abnormalities, and SAC3D1 could be a prognostic marker for HCC recurrence after surgical treatment [ 30 ].…”

Development and validation of a RNA binding protein gene pair-associated prognostic signature for prediction of overall survival in hepatocellular carcinoma

“…However, most of existing signatures have not been widely used in clinical practice, which may owe to multiple factors. First, many traditional prognostic signatures failed to validate their findings in another independent cohort [17,21]. More importantly, the diversity of data also represents a major challenge, and data processing across various sequencing platforms require suitable normalization and elimination of the batch effects.…”

“…The RBP prognostic signature was verified as a robust complement to clinical and pathological factors for the prognosis assessment of HCC patients with C-index of 0.803. We further compared the novel established signature with twelve published molecular signatures [16][17][18][19][20][21][24][25][26][27][28][29], which were all prognostic signatures for HCC survival prediction. More importantly, the C-index of the prognostic model yielded much higher value than that of other risk models (Fig.…”

“…For example, Liu et al [20] have established a novel six-gene signature for HCC prognosis prediction, but only one external validation cohort was used to validate the performance of the predicted model without comparison of its performance with other existed biomarkers. Li et al developed and identified a seven-gene signature related to the DNA repair process to predict survival in HCC, but without any external validation the performance of the predicted model [21]. However, none of these signatures have yet been widely accepted in routine clinical practice because of technical limitations and evaluation difficulties.…”