scholarly journals Downregulation of CYP2A6 and CYP2C8 in Tumor Tissues Is Linked to Worse Overall Survival and Recurrence-Free Survival from Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaojing Ren ◽  
Yuanyuan Ji ◽  
Xuhua Jiang ◽  
Xun Qi

Objective. This study aimed to evaluate the links between CYP450 family genes in tumor tissues and hepatocellular carcinoma (HCC) outcomes.Methods. Gene Expression Omnibus (GEO) databases GSE14520 and GSE36376 were used to identify differential expressed CYP450 genes between tumor and nontumor tissues and related to HCC clinicopathological features and survivals.Results. Seven CYP450 genes including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2E1, CYP3A4, and CYP4A11 were downregulated in tumor tissues, which were validated in both GSE14520 and GSE36376. HCC patients with CYP2A6 and CYP2C8 low levels in tumor tissues suffered from poorer overall survival (OS) compared to those with high CYP2A6 and CYP2C8 in GSE14520 profile (log ranksP= 0.01 andP= 0.006, respectively). In addition, HCC patients with lower CYP2A6 and CYP2C8 in tumors had worse recurrence-free survival (RFS) than those with higher CYP2A6 and CYP2C8 (log ranksP= 0.02 andP= 0.012, respectively). In GSE36376 validation dataset, HCC patients with lower CYP2A6 and CYP2C8 had worse OS and RFS than those with higher CYP2A6 and CYP2C8 (allP< 0.05), in line with results in GSE14520 dataset. Additionally, lower CYP2A6 and CYP2C8 are associated with advanced clinicopathological features including tumor staging, vascular invasion, intrahepatic metastasis, and high alpha fetoprotein (allP< 0.05).Conclusion. Downregulation of CYP2A6 and CYP2C8 in tumor tissues links to poorer OS and RFS in HCC patients.

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097714
Author(s):  
Liping Zhuang ◽  
Yuan Zhang ◽  
Zhiqiang Meng ◽  
Zongguo Yang

Objective: This study aimed to investigate the associations between RAD51AP1 and the outcomes of hepatocellular carcinoma (HCC). Methods: RAD51AP1 expression levels were compared in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset. Results: RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all P < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression ( P = 0.0034 and P = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset ( P = 0.0074 and P = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, P = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, P = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml. Conclusions: Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-Ying Huang ◽  
Jin-Guang Yao ◽  
Hong-Dong Huang ◽  
Chao Wang ◽  
Yun Ma ◽  
...  

MicroRNA-429 (miR-429) may modify the development and progression of cancers; however, the role of this microRNA in the hepatocellular carcinoma (HCC) has not been well elaborated. Here, we tested miR-429 expression in 138 pathology-diagnosed HCC cases and SMMC-7721 cells. We found that miR-429 was upregulated in HCC tumor tissues and that the high expression of miR-429 was significantly correlated with larger tumor size (odd ratio (OR), 2.70; 95% confidence interval (CI), 1.28–5.56) and higher aflatoxin B1-DNA adducts (OR = 3.13, 95% CI = 1.47–6.67). Furthermore, this microRNA overexpression modified the recurrence-free survival and overall survival of HCC patients. Functionally, miR-429 overexpression progressed tumor cells proliferation and inhibited cell apoptosis. These results indicate for the first time that miR-429 may modify HCC prognosis and tumorigenesis and may be a potential tumor therapeutic target.


2013 ◽  
Vol 31 (4) ◽  
pp. 426-432 ◽  
Author(s):  
Zhen-Wei Peng ◽  
Yao-Jun Zhang ◽  
Min-Shan Chen ◽  
Li Xu ◽  
Hui-Hong Liang ◽  
...  

Purpose To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Patients and Methods A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. Results At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. Conclusion TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.


Author(s):  
Susumu Mochizuki ◽  
Hisashi Nakayama ◽  
Yutaka Midorikawa ◽  
Tokio Higaki ◽  
Masamichi Moriguchi ◽  
...  

Objective The effect of postoperative complications including red blood transfusion (BT) on long-term survival for hepatocellular carcinoma (HCC) is unknown. The purpose of this study was to define the relationship between postoperative complications and long-term survival in patients with HCC. Methods Postoperative complications of 1251 patients who underwent curative liver resection for HCC were classified, and their recurrence-free survival (RFS) and cumulative overall survival (OS) were investigated. Results Any complications occurred in 503 patients (40%). Five-year RFS and 5-year OS in the complication group were 21% and 56%, respectively, significantly lower than the respective values of 32% ( p &lt; 0.001) and 68% ( p &lt; 0.001) in the no-complication group (n=748). Complications related to RFS were postoperative BT [Hazard ratio (HR): 1.726, 95% confidence interval (CI): 1.338–2.228, p &lt; 0.001], pleural effusion [HR: 1.434, 95% CI: 1.200–1.713, p &lt; 0.001] using Cox-proportional hazard model. Complications related to OS were postoperative BT [HR: 1.843, 95%CI: 1.380-2.462, p &lt; 0.001], ascites [HR: 1.562, 95% CI: 1.066–2.290 p = 0.022], and pleural effusion [HR: 1.421, 95% CI: 1.150–1.755, p = 0.001). Conclusions Postoperative complications were factors associated with poor long-term survival. Postoperative BT and pleural effusion, were noticeable complications that were prognostic factors for both recurrence-free survival and overall survival.


2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877800 ◽  
Author(s):  
Xi Liu ◽  
Lei Chen ◽  
Tao Zhang

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.


2019 ◽  
Vol 18 ◽  
pp. 153303381988798 ◽  
Author(s):  
Hansong Bai ◽  
Xing Luo ◽  
Dongxu Liao ◽  
Wei Xiong ◽  
Ming Zeng ◽  
...  

Objective: PTTG3P, which maps to chromosome 8q13.1, is a novel long noncoding RNA with oncogenic properties in cancers. In this study, we aimed to investigate the prognostic value of PTTG3P in terms of overall survival and recurrence-free survival and its potential regulatory network and transcription pattern in patients with hepatocellular carcinoma. Patients and Methods: An in silico analysis was performed using data from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma. Results: Results showed that the high PTTG3P expression group was consistently associated with shorter overall survival and recurrence-free survival, regardless of pathological stages or tumor grade. High PTTG3P expression was an independent indicator of shorter overall survival (hazard ratio: 2.177, 95% confidence interval: 1.519-3.121, P < .001) and recurrence-free survival (hazard ratio: 2.222, 95% confidence interval: 1.503-3.283, P < .001). The genes strongly coexpressed with PTTG3P are enriched in several KEGG pathways that are closely associated with carcinogenesis and malignant transformation of hepatocellular carcinoma. Conclusion: Based on the findings, we infer that PTTG3P expression might serve as an independent prognostic biomarker in primary hepatocellular carcinoma.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 257-257
Author(s):  
Xiao Xiang ◽  
Jian-Hong Zhong ◽  
Yang Ke ◽  
Xue-Mei You ◽  
Ning-Fu Peng ◽  
...  

257 Background: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. Methods: We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n = 155) or ADV (n = 46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free and overall survival, as well as antiviral medication costs. Results: Despite significant improvement in HBV-DNA and ALT level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2 and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, 56.4%) than in the ADV group (0%, 3.3%, 14.5%; P < 0.001). Overall survival at 1, 2, 3 years after resection was similar for the LAM group (84.5%, 69.3%, 64.6%) and the ADV group (84.1%, 77.8%, 63.4%; P = 0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, 43.9%) and the ADV group (81.1%, 66.1%, 53.0%; P = 0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, €5.6 per person per day) than in the ADV group (€2.2, €2.4, €3.1 per person per day; all P < 0.05). Conclusions: ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.


2020 ◽  
Author(s):  
WENHUA WANG ◽  
LINGCHEN WANG ◽  
XINSHENG XIE ◽  
YEHONG YAN ◽  
YUE LI ◽  
...  

Abstract BackgroundHepatocellular carcinoma (HCC) remains the most frequent liver cancer, accounting for approximately 90% of primary liver cancers worldwide. The recurrence-free survival (RFS) of HCC patients is a critical factor in devising a personal treatment plan. Thus, it is necessary to accurately forecast the prognosis of HCC patients in clinical practice.MethodsUsing The Cancer Genome Atlas (TCGA) dataset, we identified genes associated with RFS. A robust likelihood-based survival modeling approach was used to select the best genes for the prognostic model. Then, the GSE76427 dataset was used to evaluate the prognostic model’s effectiveness.ResultsWe identified 1331 differentially expressed genes associated with RFS. Seven of these genes were selected to generate the prognostic model. The validation in both the TCGA cohort and GEO cohort demonstrated that the 7-gene prognostic model can predict the RFS of HCC patients. Meanwhile, the results of the multivariate Cox regression analysis showed that the 7-gene risk score model could function as an independent prognostic factor. In addition, according to the time-dependent ROC curve, the 7-gene risk score model performed better in predicting the RFS of the training set and the external validation dataset than the classical TNM staging and BCLC. Furthermore, these seven genes were found to be related to the occurrence and development of liver cancer by exploring three other databases.ConclusionOur study identified a seven-gene signature for HCC RFS prediction that can be used as a novel and convenient prognostic tool. These seven genes might be potential target genes for metabolic therapy and the treatment of HCC.


2020 ◽  
Author(s):  
Wenhua Wang ◽  
Lingchen Wang ◽  
Xinsheng Xie ◽  
Yehong Yan ◽  
Yue Li ◽  
...  

Abstract Hepatocellular carcinoma (HCC) remains the most frequent liver cancer, accounting for approximately 90% of primary liver cancers worldwide. The recurrence-free survival (RFS) of HCC patients is a critical factor in devising a personal treatment plan. Thus, it is necessary to accurately forecast the prognosis of HCC patients in clinical practice. Using the The Cancer Genome Atlas (TCGA) dataset, we identified genes that are associated with RFS. A robust likelihood-based survival modeling approach was used to select the best genes for the prognostic model. Then, the GSE76427 dataset was used to evaluate the prognostic model’s effectiveness. We identified 1331 differentially expressed genes associated with RFS. Seven of these genes were selected to generate the prognostic model. Validation in both the TCGA cohort and the GEO cohort demonstrated that the 7-gene prognostic model has the capability of predicting the RFS of HCC patients. Meanwhile, the result of multivariate Cox regression showed that the 7-gene prognostic model could work as an independent prognostic factor. In addition, according to the time dependent ROC curve, the 7-gene prognostic model performed better in predicting the RFS of the training set and the external validation dataset than the classical TNM staging and BCLC. What’s more, these seven genes were found to be related to the occurrence and development of liver cancer by exploring other three databases. Our study identified a seven-gene signature for HCC RFS prediction that is a novel and convenient prognostic tool. The seven genes might provide potential target genes for metabolic therapy and the treatment of HCC.


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