High expression of long non-coding RNA ANRIL is associated with poor prognosis in hepatocellular carcinoma

Introduction: long non-coding RNA ANRIL (lncRNA ANRIL) has been demonstrated to play a crucial role in cancer progression. However, its effects in hepatocellular carcinoma (HCC) have not been explored. The aim of this study was to investigate the clinical significance of lncRNA NRIL in human HCC. Methods: In this study, we determined for the first time the expression of lncRNA ANRIL in human HCC by quantitative Real-time-PCR analysis. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence lncRNA ANRIL and to explore the effects of reduced lncRNA ANRIL expression on cell growth and metastasis. Results: lncRNA ANRIL expression in HCC tissues was significantly higher than in the adjacent non-tumor tissues (P < 0.05). The expression of lncRNA ANRIL was remarkably associated with the histologic grade and TNM stage of HCC patients (P < 0.05). In addition, HCC patients with higher lncRNA ANRIL expression had significantly poorer overall survival (P < 0.05). Multivariate analysis suggested that high lncRNA ANRIL expression was an independent predictor of poor prognosis (P < 0.05). Moreover, in vitro assays revealed that the decreased expression of lncRNA ANRIL could suppress the cell proliferation, migration and invasion HCC cells. Conclusions: Our results suggest that lncRNA ANRIL may serve as an efficient clinical biomarker and a therapeutic target for HCC patients.     

Up-regulation of long non-coding RNA CCAT2 correlates with tumor metastasis and poor prognosis in cervical squamous cell cancer patients

Background: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. The purpose of this study was to investigate the relationship between lncRNA CCAT2 expression and cervical squamous cell cancer susceptibility and prognosis. Methods: Expression levels of lncRNA CCAT2 in 123 cervical squamous cell tumor specimens were determined by quantitative real-time PCR (qRT-PCR), to clarify the clinical significance of lncRNA CCAT2 in cervical squamous cell cancer, we further discussed the relationship between lncRNA CCAT2 expression and overall survival (OS) and progression-free survival (PFS). Results: In the present study, we found that lncRNA CCAT2 was up-regulated in cervical squamous cell cancer tissues compared to the adjacent non-tumor tissues. In addition, the high lncRNA CCAT2 expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (P<0.05). Furthermore, patients with high expression of lncRNA CCAT2 had poor OS (HR=2.813, 95% CI: 1.504-6.172; P=0.017), and PFS rates (HR=3.072, 95% CI: 1.716-8.174; P=0.008). Multivariate Cox proportional hazard model analysis demonstrated that high lncRNA CCAT2 expression was an independent poor prognostic factor for cervical squamous cell cancer patients. Conclusions: Our study suggested that high expression of lncRNA CCAT2 is related to the prognosis of cervical squamous cell cancer; it may be a new prognostic biomarker and potential therapeutic target for cervical squamous cell cancer intervention.     

Prognostic significance of long non-coding RNA PCAT-1 expression in human hepatocellular carcinoma

Background: Long non-coding RNAs (lncRNAs) play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in hepatocellular carcinoma (HCC) are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA PCAT-1 expression in HCC and evaluate its clinical significance in the development and progression of HCC. Methods: We examined the expression of PCAT-1 in 117 HCC tissues and adjacent non-tumor tissues using quantitative real-time-PCR and analyzed its correlation with the clinical parameters. Results: Our data showed that PCAT-1 expression in HCC tissues was significantly increased compared with adjacent non-tumor tissues (P<0.05). Up-regulated expression of PCAT-1 was significantly associated with TNM stage and metastasis (P<0.05), but not other clinical parameters. Moreover, Kaplan-Meier survival analysis showed that a high expression level of PCAT-1 resulted in a significantly poor overall survival of HCC patients. The multivariate Cox regression analysis demonstrated that PCAT-1 expression level was an independent prognostic factor for the overall survival rate of HCC patients. Conclusions: Our data suggested that the increased expression of PCAT-1 was associated with advanced clinical parameters and poor overall survival of HCC patients, indicating that PCAT-1 up-regulation may serve as a novel biomarker of poor prognosis in HCC patients.     

Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma

Introduction: Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNA GAS5 has recently been identified to be involved in tumorigenesis of several cancers such as breast cancer, lung cancer and renal cancer. However, the regulation of GAS5 in hepatocellular carcinoma (HCC) has not yet been reported before. Methods: Expression of GAS5 in tumor and their normal matched tissues was determined by quantitative real-time PCR in n = 71 HCC patients, and its association with overall survival of patients was analyzed by statistical analysis. Results: The expression level of GAS5 was reduced in HCC in comparison to normal matched tissues (P < 0.05). It is also proved that GAS5 expression was to be associated with HCC tumor size, lymphnode metastasis and clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that low GAS5 expression was associated with poor prognosis in HCC patients. GAS5 expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. Conclusions: The study proved for the first time that GAS5 down regulated in a majority of HCC patients. Our results indicated that GAS5 expression was an independent prognostic factor for patients with liver cancer, which might be a potential valuable biomarker for HCC.     

乙肝病毒促进肝癌细胞系的转移侵袭力

目的探讨乙肝病毒(HBV)对肝癌细胞转移能力的影响及其可能机制。方法以初始汇合度为30%,将3种细胞系HL-7702(人正常肝细胞系)、HepG2(未转染HBV-DNA的人肝癌细胞系)、HepG2.2.15(稳定转染HBV-DNA的人肝癌细胞系)种植于96孔板中,待细胞增殖至70%汇合时,利用划痕器制造划痕伤口,置于活细胞动态成像系统中进行多时间点的显微拍照与数据采集,计算相对伤口密度(RWD),并通过免疫荧光染色与Western blot技术测定细胞中Eph A2蛋白表达,分析其与RWD值的相关性。结果细胞迁移实验中,划痕后24~96 h,HL-7702组RWD显著高于HepG2与HepG2.2.15组(P0.01),划痕后72~144 h,HepG2.2.15组RWD显著高于HepG2组(P0.01);细胞侵袭实验中,HL-7702细胞因不能穿过基质胶,而无RWD值;划痕后72~144 h,HepG2.2.15组RWD显著高于HepG2组(P0.05或P0.01)。Eph A2表达:与HL-7702组比较,HepG2与HepG2.2.15组细胞中Eph A2表达水平显著升高(P0.01),其中HepG2.2.15组中Eph A2表达水平显著高于HepG2组(P0.01),且两组肝癌细胞中Eph A2的表达量与划痕实验的RWD值呈显著正相关(迁移实验:P0.01;侵袭实验:P0.01)。结论乙肝病毒可能促进肝癌细胞的迁移和侵袭能力,其机制可能与上调Eph A2的异常表达有关。     

The expression of long non-coding RNA HOTAIR in advanced hepatocellular carcinoma and its prognostic correlation with sunitinib therapy

IntroductionThe study was designed to assess the expression of long non-coding RNA HOTAIR (lncRNA HOTAIR) in tissues and peripheral blood of patients with advanced hepatocellular carcinoma (HCC). In addition, we also investigated the prognostic correlation between the expression level of lncRNA HOTAIR in tumour tissues and peripheral blood of patients with advanced HCC and sunitinib monotherapy.Material and methodsA total of 60 patients with advanced HCC who received sunitinib monotherapy and another 60 healthy individuals who were examined at the physical examination centre during the same period were included in the study. Real-time quantitative PCR (RT-QPCR) was used to determine the relative expression of lncRNA HOTAIR in tumour tissue, adjacent tissue, and peripheral blood of HCC patients as well as peripheral blood of healthy controls. Moreover, the clinicopathological information, overall survival (OS), and progression-free survival (PFS) were collected, followed by correlation analysis with lncRNA HOTAIR expression.ResultsThe expression of lncRNA HOTAIR was significantly higher in tumour tissues compared to that in adjacent tissues (t = 9.03, p < 0.001). The expression of lncRNA HOTAIR in peripheral blood of HCC patients was higher than that in healthy controls (t = 8.04, p < 0.001). There was a correlation between the expression of lncRNA HOTAIR in tumour tissue and peripheral blood in HCC patients (r = 0.638, p < 0.001). Patients with low lncRNA HOTAIR expression in tumour tissues harboured significantly longer OS (13.4 vs. 9.5, p < 0.001) and PFS (8.4 vs. 6.2, p < 0.001) compared to those with high expression. Consistently, patients with low lncRNA HOTAIR expression in peripheral blood had significantly prolonged OS (12.8 vs. 9.1, p < 0.001) and PFS (8.9 vs. 6.4, p < 0.001) compared to those with high expression. Patients with low expression both in tumour tissue and peripheral blood had prolonged OS (14.3 vs. 8.8, p < 0.001) and PFS (10.6 vs. 6.0, p < 0.001) compared to the rest of the patients. Cox regression analysis indicated that the expression level of lncRNA HOTAIR in tumour tissue and peripheral blood was an independent predictive factor of OS and PFS in patients with advanced HCC treated by sunitinib.ConclusionsThe expression of lncRNA HOTAIR was up-regulated in tumour tissue and peripheral blood in patients with advanced HCC. In addition, the expression level of lncRNA HOTAIR was one of the indicators predicting the effectiveness of sunitinib therapy.     

Long non-coding RNA CCAT2 is up-regulated in gastric cancer and associated with poor prognosis

Introduction: Dysregulation of long non-coding RNAs (lncRNAs) play important roles in tumor progression. The aim of our study was to explore the clinicopathologic and prognostic significance of lncRNA CCAT2 expression in human gastric cancer. Methods: Expression levels of lncRNA CCAT2 in 85 pairs of gastric cancer and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival and progression-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Expression levels of lncRNA CCAT2 in gastric cancer tissues were significantly higher than those in adjacent non-tumor tissues. By statistical analyses, high lncRNA CCAT2 expression was observed to be closely correlated with higher incidence of lymph node metastasis and distance metastasis. Moreover, patients with high lncRNA CCAT2 expression had shorter overall survival and progression-free survival compared with the low lncRNA CCAT2 group. Multivariate analyses indicated that high lncRNA CCAT2 expression was an independent poor prognostic factor for gastric cancer patients. Conclusions: Our results suggested that up-regulation of lncRNA CCAT2 was correlated with gastric cancer progression, and lncRNA CCAT2 might be a potential molecular biomarker for predicting the prognosis of patients.     

Increased expression of miR-21 predicts poor prognosis in patients with hepatocellular carcinoma

Background: MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC) development and progression. Aberrant miR-21 expression has been reported in several cancers. However, the clinical significance of miR-21 in human HCC is still unclear. Methods: A total of 112 patients with primary HCC who underwent a curative liver resection were included in this retrospective study. The differentially expressed amount of the miR-21 was validated by quantitative real-time PCR (qRT-PCR). Survival rate was analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Multivariate analysis of the prognostic factors was performed with Cox regression model. Results: As revealed by qRT-PCR analysis, miR-21 expression was significantly upregulated in HCC tissues when compared with adjacent non-tumor tissues (P<0.05). High miR-21 expression level was observed to be closely correlated with tumor differentiation, TNM stage and vein invasion (P<0.05). Patients who had high miR-21 expression had a shorter overall survival than patients who had low miR-21 expression (P<0.05). Moreover, multivariate analysis of the prognosis factors with a Cox proportional hazards model showed that high miR-21 expression was a significant independent predictor of poor survival in HCC (P<0.05). Conclusion: Our results suggested that increased expression of miR-21 was significantly correlated with tumor progression and could be a novel potential biomarker for HCC prognosis.     

ARP3 promotes tumor metastasis and predicts a poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Therefore, the study of the precise molecular mechanism underlying hepatocarcinogenesis has profound significance. In this study, we found that the expression of ARP3 was significantly up-regulated in HCC tissues and cell lines. Studies in liver cancer specimens showed that the expression of ARP3 is closely related to the pathological grade, distant metastasis and vascular invasion of HCC. According to the results of multivariate analysis, ARP3 is an independent prognostic factor for HCC patients. In vitro, knockdown of ARP3 expression significantly inhibited the invasion and migration of HCC cells and altered the expression of EMT markers. Based on the above conclusions, we conclude that ARP3 may be a potential prognostic indicator and therapeutic target for HCC patients.     

Insulin-like growth factor binding protein-1 inhibits cancer cell invasion and is associated with poor prognosis in hepatocellular carcinoma

Insulin-like growth factor binding protein-1 (IGFBP-1) plays an important role in the development and progression of cancer. However, the expression of IGFBP-1 remains equivocal, and little is known about its clinicopathological significance and prognostic value in hepatocellular carcinoma (HCC). In this study, we evaluated the expression of IGFBP-1 in 90 paired HCC tissues and adjacent non-cancerous liver tissues and analyzed its clinical and prognostic significance. The results showed that IGFBP-1 was detected in cytoplasm as well as cell nucleus, and down-regulated in HCC tissues compared to the adjacent non-cancerous liver tissues. The decreased expression of IGFBP-1 was correlated with tumor differentiation, liver cirrhosis, microvascular invasion or metastasis, TNM stage and poor survival. Moreover, low levels of IGFBP-1 may be an independent prognostic indicator for the survival of patients with HCC. We also evaluated its function by adding recombinant IGFBP-1 to the cultured HCC cell lines HepG2 and MHCC97-H. The result of the invasion chamber assay showed that IGFBP-1 could inhibit the invasion of HepG2 and MHCC97-H. MMP-9 secretion by these cells was significantly decreased when the cells were treated with IGFBP-1. Our results suggest that IGFBP-1 inhibits the invasion and metastasis of HCC cells and that IGFBP-1 may be useful as a valuable marker for the prognosis of patients with HCC.     

High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma

Introduction: Long non-coding RNAs (lncRNAs) play a key role in cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNAs SPRY4-IT1 has recently been identified to be involved in tumorigenesis of several cancers such as non-small cell lung cancer and esophageal squamous cell carcinoma. However, the role of SPRY4-IT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: The expression of SPRY4-IT1 was examined in ccRCC patients and renal cancer cell lines by using quantitative real-time PCR (qRT-PCR). The relationship between SPRY4-IT1 level and clinicopathological parameters of ccRCC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in renal cancer cell line 786-O. In vitro assays were performed to further explore its role in renal cancer progressio. Results: The relative level of SPRY4-IT1 was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. And higher expression of SPRY4-IT1 was found in renal cancer cell lines compared with the normal human proximal tubule epithelial cell line HK-2. The ccRCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. Multivariate analyses by Cox’s proportional hazard model revealed that expression of SPRY4-IT1 was an independent prognostic factor in ccRCC. In vitro assays, our results indicated that knockdown of SPRY4-IT1 reduced renal cancer cell proliferation, migration, and invasion. Conclusions: Our data suggested that lncRNA SPRY4-IT1 might be considered as a potential prognostic indicator and a potential target for therapeutic intervention in RC.     

Overexpression of long non-coding RNA CCAT1 is a novel biomarker of poor prognosis in patients with breast cancer

Introduction: Recent studies have demonstrated that lncRNA CCAT1 was increased in many types of cancers and was involved in various cellular processes related to carcinogenesis. However, the clinical significance and prognostic value of lncRNA CCAT1 in breast cancer (BC) haven’t been investigated. Methods: Expression levels of lncRNA CCAT1 in 92 pairs of BC cancer tissues and adjacent normal tissues were detected by quantitative real-time PCR. In order to determine its prognostic value, overall survival and progression-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Expression levels of lncRNA CCAT1 in BC tissues were significantly higher than those in adjacent normal tissues. High expression of lncRNA CCAT1 was associated with differentiation grade, TNM stage, and lymph node metastases. Kaplan-Meier analysis with the log-rank test indicated that high expression of lncRNA CCAT1 had a decreased overall survival and progression-free survival. Multivariable analysis was further identified high expression of lncRNA CCAT1 as an independent prognosis factor for overall survival and progression-free survival. Conclusions: Our findings provided that the expression of lncRNA CCAT1 was up-regulated in BC and associated with overall survival as well as progression-free survival, suggesting that lncRNA CCAT1 could be a potential prognostic biomarker for BC progression.     

Decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma

Introduction: Long non-coding RNA MEG3 (lncRNA MEG3) has been showed to involve in a variety of cancers. However, the association between lncRNA MEG3 expression level and the prognosis of osteosarcoma is still unclear. Methods: The expression levels of lncRNA MEG3 in osteosarcoma tissues and adjacent non-tumor tissues were detected using quantitative real-time PCR (qRT-PCR). Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: Our findings showed that expression of lncRNA MEG3 was clearly lower in osteosarcoma tissues compared with adjacent non-tumor tissues. The expression of lncRNA MEG3 was associated with clinical stage and distant metastasis (P<0.05). Kaplan-Meier analysis showed that patients with low lncRNA MEG3 expression had a shorter overall survival (log-rank test, P<0.05). Furthermore, multivariate analysis revealed that decreased expression of lncRNA MEG3, advanced clinical stage and distant metastasis were all independent predictors to overall survival of osteosarcoma patients. Conclusions: Downregulation of lncRNA MEG3 was associated with poor overall survival of osteosarcoma. LncRNA MEG3 could be a useful biomarker for progression and prognosis of osteosarcoma.     

Decreased expression of serum miR-424 correlates with poor prognosis of patients with hepatocellular carcinoma

Background: MicroRNAs (miRNAs) play important roles in many important cellular processes and deregulation of miRNAs is linked to many human diseases including cancer. Although miR-424 has been demonstrated to inhibit progression of hepatocellular carcinoma (HCC), its expression level in serum samples and the potential clinical values remain unknown. Materials and methods: The expression level of miR-424 in the serum clinical samples from HCC patients and healthy volunteers were determined by qRT-PCR. Then the association of serum miR-424 expression level with various important clinicopathological parameters and survival rates was evaluated. Multivariate Cox regression analysis was used to identify the independent risk factors for HCC. Results: The expression level of serum miR-424 was significantly decreased in patients with HCC compared with the healthy volunteers (P<0.01). Reduced expression of serum miR-424 was associated with serum AFP (P=0.048), vein invasion (P=0.006) and TNM stage (P=0.003). In addition, survival analysis showed that HCC patients with lower serum miR-424 expression suffered poorer overall survival (P=0.018) and disease free survival (P=0.008). Moreover, serum miR-424 was demonstrated to be an independent risk factor for HCC. Conclusions: Our findings provide the compelling evidence that the decreased expression of serum miR-424 may serve as a novel biomarker to predict the unfavorable prognosis of HCC patients.