scholarly journals MicroRNA-429 Modulates Hepatocellular Carcinoma Prognosis and Tumorigenesis

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.

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Yi-Xiao Liu ◽  
Xi-Dai Long ◽  
Zhi-Feng Xi ◽  
Yun Ma ◽  
Xiao-Ying Huang ◽  
...  

MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66–8.47) and overall survival (HR=3.58, 95% CI = 2.34–5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.


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.


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.


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.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Jian-Hong Zhong ◽  
Le-Qun Li ◽  
Xin-Ping Ye ◽  
Yang Ke ◽  
Lin Wang ◽  
...  

427 Background: Official guidelines and retrospective studies have different view on the role of hepatic resection (HR) for patients with large (≥5 cm) multinodular (≥2) hepatocellular carcinoma (HCC) and those involving macrovascular invasion (MVI). We aim to evaluate the efficacy and its variation trend and the safety of HR for these patients in three tertiary care settings. Methods: A consecutive sample of 1,824 patients with Child-Pugh A liver function and large/multinodular HCC or involving MVI and who underwent initial HR were divided into four groups: large/multinodular HCC of the previous (2000-2004, n = 496) and recent five years (2005-2010, n = 765), involving MVI of the previous (n = 242) and recent five years (n = 321). Results: Among our patient sample, the hospital mortality was less than 5% and had a downward trend. Moreover, patients in recent five years have statistically significant longer survival time. Among patients with large/multinodular HCC, patients in recent five years showed a significantly better overall survival than those in previous five years at 1-year (92% vs. 84%), 3-year (69% vs. 61%), and 5-year (45% vs. 40%) (P = 0.004). Moreover, among patients involving MVI, overall survival in recent five years was significantly higher at 1-year (83% vs. 78%), 3-year (50% vs. 41%), and 5-year (25% vs. 17%) (P= 0.033). However, the disease-free survival of recent five years was only slightly higher than that of the previous five years in the two subgroups. Conclusions: HR offers good overall survival for patients with resectable large/multinodular HCC or those involving MVI and with preserved liver function. Outcomes have tended to improve in recent decade.


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.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 170-170 ◽  
Author(s):  
A. R. Limaye ◽  
R. Cabrera

170 Background: The Milan criteria are utilized to predict outcomes in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT). Though the survival of these patients has significantly improved since the adoption of these criteria, the risk of recurrence after LT is as high as 20 percent. One limitation of the Milan criteria is the lack of any estimation of tumor biology. The neutrophil-lymphocyte ratio (NLR) has been proposed as a peripheral surrogate for tumor biology. The predictive power of the NLR has been demonstrated for several solid tumors, and early evidence points to a role in HCC. We hypothesize that the NLR is predictive of overall survival and recurrence-free survival in patients with HCC who undergo LT. Methods: This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We defined an elevated NLR as a ratio of five or greater. Results: We identified 160 patients who underwent LT for HCC, 28 of whom had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival for subjects with an elevated NLR (1-year cumulative survival 70% ± 0.08, 3-year cumulative survival 48% ± 0.09, 5-year cumulative survival 38% ± 0.11) was significantly lower than for subjects with a normal NLR (1-year survival 80% ± 0.04, 3-year survival 75% ± 0.04, 5-year survival 68% ± 0.06). On univariate analysis, seven factors (including an elevated NLR) predicted decreased overall and recurrence-free survival. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of overall survival. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of recurrence-free survival. Conclusions: Preoperative NLR is a powerful independent predictor of overall survival and recurrence-free survival in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the MELD score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplant. No significant financial relationships to disclose.


2019 ◽  
Vol 7 (5) ◽  
pp. 354-360 ◽  
Author(s):  
Ya-Bin Wang ◽  
Bo-Xuan Zhou ◽  
Yun-Biao Ling ◽  
Zhi-Yong Xiong ◽  
Rui-Xi Li ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. Methods We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. Results ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan–Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. Conclusions ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.


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