High-density lipoprotein cholesterol level as an independent protective factor against aggravation of acute pancreatitis: a case-control study.

Background and aims: At present, evidence on the association between high-density lipoprotein cholesterol (HDL-C) levels and aggravation of acute pancreatitis (AP) is limited. This study aimed to investigate the relationship between the lowest HDL-C level during intensive care units (ICU) stay and AP aggravation and to determine the optimum cutoff lowest HDL-C level. Methods: Patients admitted to the ICU of the Shandong Provincial Hospital for AP from 2015 to 2021 were included. The lowest HDL-C level during ICU stay was set as the independent variable, and the progression or non-progression to severe AP (SAP) was set as the dependent variable. Univariate and multivariate analyses were performed to determine the relationship between the two variables, and receiver operating characteristic (ROC) curves were plotted to analyze the predictive ability of the lowest HDL-C level for progression to SAP. Results: This study included 115 patients. The difference in the lowest HDL-C level between the SAP and moderately SAP groups was significant (P < 0.05). After adjusting for covariates, the lowest HDL-C level showed a negative correlation with the occurrence of SAP, with a relative risk of 0.897 (95% confidence interval: 0.827-0.973). The area under the ROC curve for prediction of AP aggravation by the lowest HDL-C level was 0.707, and the optimum cutoff lowest HDL-C level was 0.545 mmol/L. Conclusion: No less than 0.545 mmol/L of the HDL-C level during ICU stay may be an independent protective factor for the aggravation of AP.

Intraductal papillary mucinous neoplasm of the biliary tract in the caudate lobe of the liver: a case report and literature review.

An intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) in the caudate lobe of the liver is a rare tumor originating from the bile duct. Approximately 40% of the intraductal papillary neoplasms of the biliary tract (IPNB) secrete mucus and can grow in the intrahepatic or extrahepatic bile ducts. A 65-year-old woman presented with recurrent episodes of right upper pain. She developed her first episode 8 years ago, which resolved spontaneously. The frequency of symptoms has increased in the last 2 years. She underwent laparoscopic hepatectomy and choledochal exploration and was pathologically diagnosed with a rare BT-IPMN of the caudate lobe after admission. Here, we review studies on IPNB cases and systematically describe the pathological type, diagnosis, and treatment of IPNB to provide a valuable reference for hepatobiliary surgeons in the diagnosis and treatment of this disease.

Silencing lncRNA HCG18 regulates GPX4-inhibited ferroptosis by adsorbing miR-450b-5p to avert sorafenib resistance in hepatocellular carcinoma.

Ferroptosis is potential to relieve drug resistance in hepatocellular carcinoma (HCC). Glutathione peroxidase 4 (GPX4) is a critical modulator of ferroptosis. This study discussed the mechanism of GPX4-inhibited ferroptosis in sorafenib resistance in HCC. HCG18 in HCC cells was detected. Sorafenib resistant (SR) cell line Huh7-SR cells were treated with sorafenib (0, 2.5, 5, 7.5, 10 µM). After silencing HCG18 in Huh7-SR cells, cell activity, proliferation and apoptosis were detected. The levels of iron, the concentration of MDA, GSH and lipid reactive oxygen species (ROS) were measured to evaluate the ferroptosis. The downstream mechanism of HCG18 was predicted and verified. Huh7-SR cells were infected with lentivirus sh-HCG18 to establish xenograft tumor model. HCG18 was elevated in HCC cells and associated with sorafenib resistance. Silencing HCG18 inhibited cell proliferation, promoted apoptosis, and impaired sorafenib resistance. Ferroptosis was inhibited in Huh7-SR cells, while silencing HCG18 inhibited sorafenib resistance by promoting ferroptosis. GPX4 overexpression averted the promotion of sh-HCG18 on ferroptosis, thereby reducing sorafenib resistance. HCG18 sponged miR-450b-5p to regulate GPX4. Collectively, Silencing HCG18 inhibits GPX4 by binding to miR-450b-5p, promotes GPX4-inhibited ferroptosis, and averts sorafenib resistance in HCC.

Prognostic analysis of radical resection for iCCAphl and iCCApps: A retrospective cohort study.

Backgroud: At present, there is no definitive conclusion about the relative prognostic factors on intrahepatic cholangiocarcinoma perihilar large duct type (iCCAphl) and iCCA peripheral small duct type (iCCApps). Aim of the study: To compare the prognoses of two different types of iCCA, and identify the independent risk factors affecting the long-term survival of patients undergoing radical resection for iCCA. Methods: This study included 89 patients with iCCA who underwent radical resection at the Department of Hepatobiliary Surgery of the East Yard of the Shandong Provincial Hospital between January 2013 and March 2022. According to the tumor origin, these patients were divided into the iCCAphl group (n = 37) and iCCApps group (n = 52). The prognoses of the two groups were compared using Kaplan-Meier analysis, whereas the independent risk factors of their prognoses were identified using Cox univariate and multivariate regression analyses. Results: In the iCCApps group, the independent risk factors for overall survival included diabetes history (p = 0.006), lymph node metastasis (p = 0.040), and preoperative carbohydrate antigen 19-9 (p = 0.035). In the iCCAphl group, the independent risk factors for overall survival included multiple tumors (p = 0.010), tumor differentiation grade (p = 0.008), and preoperative jaundice (p = 0.009). Conclusions: Among the iCCA patients who underwent radical resection, the long-term prognosis of iCCApps maybe better than that of iCCAphl. The prognoses of these two types of iCCA were affected by different independent risk factors.

Clinical utility of the pancreatitis activity scoring system in severe acute pancreatitis.

Objective: To analyze clinical utility of pancreatitis activity scoring system (PASS) in prediction of persistent organ failure, poor prognosis, and in-hospital mortality in patients with moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) admitted to the intensive care unit (ICU). Methods: The study included a total of 140 patients with MSAP and SAP admitted to the ICU of Shandong Provincial Hospital from 2015 to 2021. The general information, biochemical indexes and PASS scores of patients at ICU admission time were collected. Independent risk factors of persistent organ failure, poor prognosis and in-hospital mortality were analyzed by binary logistic regression. Through receiver operating characteristic curve (ROC), the predictive ability of lactic acid, procalcitonin, urea nitrogen, PASS, and PASS in combination with urea nitrogen for the three outcomes was compared. The best cut-off value was determined. Results: Binary logistic regression showed that PASS might be an independent risk factor for patients with persistent organ failure (odds ratio [OR]: 1.027, 95% confidence interval [CI]: 1.014-1.039), poor prognosis (OR: 1.008, 95% CI: 1.001-1.014), and in-hospital mortality (OR: 1.009, 95% CI: 1.000-1.019). PASS also had a good predictive ability for persistent organ failure (area under the curve (AUC) = 0.839, 95% CI: 0.769-0.910) and in-hospital mortality (AUC = 0.780, 95% CI: 0.669-0.891), which was significantly superior to lactic acid, procalcitonin, urea nitrogen and Ranson score. PASS (AUC = 0.756, 95% CI: 0.675-0.837) was second only to urea nitrogen (AUC = 0.768, 95% CI: 0.686-0.850) in the prediction of poor prognosis. Furthermore, the predictive power of urea nitrogen in combination with PASS was better than that of each factor for persistent organ failure (AUC = 0.849, 95% CI: 0.779-0.920), poor prognosis (AUC = 0.801, 95% CI: 0.726-0.876), and in-hospital mortality (AUC = 0.796, 95% CI: 0.697-0.894). Conclusion: PASS was closely correlated with the prognosis of patients with MSAP and SAP. This scoring system may be used as a common clinical index to measure the activity of acute pancreatitis and evaluate disease prognosis.

Role of Matrix Metallopeptidase 12 in the Development of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to investigate the role of matrix metallopeptidase 12 (MMP-12) in the development of hepatocellular carcinoma (HCC). Materials and Methods: A total of 343 HCC patients were retrospectively analyzed. MMP-12 expression was detected by immunohistochemical staining and the correlation between MMP-12 expression and clinical features was analyzed. Serum interleukin-6 (IL-6) and IL-10 levels were detected by an enzyme-linked immunosorbent assay (ELISA). Survival analysis was performed using the Kaplan-Meier method and PD-L1 expression in T cells was detected by flow cytometry. Results: MMP-12 expression in HCC tissues showed no correlation with age, gender, viral infection, cirrhosis, Child-Pugh score, alpha-fetoprotein levels, or Barcelona-Clinic Liver Cancer stage. However, higher levels of MMP-12 expression were correlated with increased tumor size, poorer tumor cell differentiation, higher TNM stage, and poorer prognosis. Moreover, MMP-12 expression was positively correlated with PD-L1 expression. Further analysis indicated that the regulation of PD-L1 expression by MMP-12 may occur through the IL-6-signaling pathway. Conclusions: Higher levels of MMP-12 expression indicated a poorer prognosis. PD-L1 expression was positively correlated with MMP-12 expression, indicating that MMP-12 may promote the development of HCC through the up-regulation of PD-L1.

Ubiquitin-conjugating enzyme E2T regulates cell proliferation and migration in cholangiocarcinoma.

Ubiquitin-conjugating enzyme E2T (UBE2T) is overexpressed in several human cancer cells, but a role in cholangiocarcinoma (CAA) progression has not been investigated. We analyzed the expression of UBE2T in CAA tissues. Then, we generated UBE2T deregulation models in which it was overexpressed or silenced, and examined the effects on CAA malignant progression by flow cytometry, western blot, MTT assay, wound healing assay and transwell assay. We report the involvement of UBE2T in CAA malignant progression. UBE2T was found to be highly expressed in human CAA cells both in vitro and in vivo. Overexpression of UBE2T significantly enhanced epithelial-to-mesenchymal transition, proliferation, migration and invasion of CAA cells in vitro, while silencing UBE2T had opposing effects. Furthermore, UBE2T appears to exert its effects via the mammalian target of rapamycin (mTOR) pathway as the cellular effects caused by UBE2T overexpression are inhibited by the mTOR inhibitor rapamycin. Our findings suggest that UBE2T may have potential as a new therapeutic target for the prevention or treatment of CAA.

Prognostic value of glucose transporter 3 expression in hepatocellular carcinoma.

Determining an effective biomarker for predicting the prognosis of patients with hepatocellular carcinoma (HCC) may improve patient survival rates. The present study aimed to investigate the expression of glucose transporter 3 (GLUT-3) in HCC and to determine its predictive value for the survival of patients with HCC. Immunohistochemistry was used to detect GLUT-3 expression in HCC tissues of 275 and 140 patients with HCC from training and validation cohorts, respectively. The association between GLUT-3 expression and the clinicopathological characteristics of patients with HCC, and between GLUT-3 expression and patient survival rates were analyzed. The predictive value of GLUT-3 expression was confirmed using the validation cohort. The results demonstrated that the high GLUT-3 expression in HCC tissues was significantly associated with elevated α-fetoprotein level, large tumor size, poor histological differentiation and Tumor-Node-Metastasis stages III and IV (P<0.05). In addition, GLUT-3 high expression was also significantly associated with reduced overall survival of patients with HCC in the training and validation cohorts. In conclusion, the results from the present study suggested that GLUT-3 may be considered as a potential independent prognostic factor for predicting the survival of patients with HCC.

Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma.

AIM: To construct a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis with high efficiency. METHODS: Differentially expressed lncRNAs (DELs) between HCC specimens and peritumor liver specimens were identified using the edgeR package to analyze The Cancer Genome Atlas (TCGA) LIHC dataset. Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival (OS) in a training set. These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model. Those lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula. The prognostic value of this formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lncRNAs in the signature. RESULTS: Based on lncRNA expression profiling of 370 HCC patients from the TCGA database, we constructed a 5-lncRNA signature (AC015908.3, AC091057.3, TMCC1-AS1, DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis. HCC patients with high-risk scores based on the expression of the 5 lncRNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups. Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lncRNAs was independent of clinicopathological parameters. A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lncRNA signature showed improved prognostic power compared with the other two signatures. Functional enrichment analysis indicated that the 5 lncRNAs were potentially involved in metabolic processes, fibrinolysis and complement activation. CONCLUSION: Our present study constructed a 5-lncRNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.

Insulin-like growth factor-1 induces epithelial-mesenchymal transition in hepatocellular carcinoma by activating survivin.

Insulin-like growth factor-1 (IGF-1), a small polypeptide hormone similar to insulin in protein structures, has been identified as an activator of epithelial-mesenchymal transition (EMT) pathways in several types of cancers. As a member of the inhibitor of apoptosis protein (IAP) family, survivin is implicated in the EMT of some cancers. However, the role of survivin on IGF-1-mediated EMT of hepatocellular carcinoma (HCC) has not been clarified. In the present study, we demonstrated that survivin was involved in the EMT process induced by IGF-1 in HCC cell line SMMC7721. With administration of different concentrations of IGF-1, survivin mRNA and protein expression were significantly increased and stimulated EMT in the tested cell line, while the increased invasive and migratory abilities of HCC cells and activation of the EMT process induced by IGF-1 were reversed after silencing of survivin expression by transfecting small interfering RNA. This was further confirmed by the observation of morphological changes, the decrease of invasive and migratory abilities and the downregulation of EMT markers, N-cadherin, vimentin and Snail, and the upregulation of E-cadherin. In conclusion, survivin may play a vital role in the IGF-1 signaling pathway by mediating EMT in HCC through the upregulation of the expression of EMT markers, and the knockdown of survivin expression may suppress the metastasis of HCC, which may provide new insights for the molecular therapy of HCC patients in clinical treatment.

Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo.

Metformin, an oral biguanide drug used to treat type 2 diabetes, has displayed anticancer activities in several types of cancer cells. The combination of gemcitabine and cisplatin is the standard chemotherapy regimen for cholangiocarcinoma, but its benefit is limited. The present study aimed to investigate whether metformin could enhance the activities of gemcitabine and cisplatin against cholangiocarcinoma, and the underlying mechanisms. Metformin inhibited the proliferation of human cholangiocarcinoma RBE and HCCC-9810 cells and induced cell cycle arrest at the G0/G1 phase by increasing the activation of AMP-activated protein kinase (AMPK) pathways. Metformin upregulated the expression of p21Waf1 and p27kip1, and downregulated the expression of cyclin D1, a key protein required for cell cycle progression. The combination of gemcitabine and cisplatin inhibited the proliferation and induced the apoptosis of human cholangiocarcinoma cells by inducing the phosphorylation of AMPK, downregulating cyclin D1, and activating caspase-3. Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3. Given that metformin has been used to treat type 2 diabetes patients for over half a century due to its superior safety profile, the results presented here indicate that metformin may be a potent agent for enhancing the efficacy of gemcitabine and cisplatin in the treatment of cholangiocarcinoma.

miR-1299 suppresses cell proliferation of hepatocellular carcinoma (HCC) by targeting CDK6.

microRNA (miRNA) plays critical role in HCC initiation and development, many miRNAs have been reported to regulate HCC progression. In this study, we studied the role of miR-1299 in cell proliferation of HCC. We found miR-1299 was significantly downregulated in HCC cells and tissues. miR-1299 overexpression inhibited cell proliferation and arrested cell cycle in G0/G1 phase analyzed by MTT assay, soft agar assay, BrdU cell proliferation assay and cell cycle assay, while miR-1299 knockdown promoted cell proliferation and accelerated G1/S transition. Further analysis suggested the key regulator of G1/S transition, cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited CDK6 expression and bound to the 3'UTR of CDK6. When double knockdown of miR-1299 and CDK6 promoted cell proliferation copied the phenotype caused by miR-1299 overexpression, suggesting miR-1299 inhibits cell proliferation by targeting CDK6. In summary, our data revealed miR-1299 inhibits cell proliferation, and might be a target for HCC therapy.

MiR-1180 promoted the proliferation of hepatocellular carcinoma cells by repressing TNIP2 expression.

MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory function, playing crucial roles in cancer development and progression of hepatocellular carcinoma (HCC). Previous studies have indicated that miR-1180 was implicated in diverse biological processes. However, the underlying mechanism of miR-1180 in HCC has not been intensively investigated. In this study, we aimed to investigate the role of miR-1180 and its target genes in HCC. We found that miR-1180 expression was significantly increased in HCC cells and clinical tissues compared with their corresponding controls. Overexpression of miR-1180 promoted cell proliferation in HCC cell line HepG2. TNFAIP3 interacting protein 2 (TNIP2), a potential target gene of miR-1180, and were validated by a luciferase assay. Further studies revealed that miR-1180 regulated cell proliferation of HCC by directly suppressing TNIP2 expression and the knockdown of TNIP2 expression reversed the effect of miR-1180-in on HCC cell proliferation. In summary, our data indicated that miR-1180 might act as a tumor promoter by targeting TNIP2 during development of HCC.

Interaction Between Polymorphisms of IFN-γ and MICA Correlated with Hepatocellular Carcinoma.

BACKGROUND We explored the relationship of interferon-γ (IFN-γ) and MHC class-I chain related gene A (MICA) genes polymorphisms with hepatocellular carcinoma (HCC) risk, and tried to determine whether the interaction existed between these two genes polymorphisms on the basis of HCC. MATERIAL AND METHODS Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the genotypes of the 3 single-nucleotide polymorphisms (SNPs) and to analyze the correlation of each SNP with HCC susceptibility in 120 HCC patients and 124 healthy people. The association strength between the 3 SNPs and HCC is represented with odds ratio (OR) and 95% confidence interval (95% CI). Hardy-Weinberg equilibrium (HWE) was tested by χ2 test in the control group. RESULTS GG genotype of IFN-γ rs2069727 polymorphism had apparently different distributions in case and control groups (P<0.05), and might confer increased risk of HCC (OR=3.40, 95%CI=1.23-9.38). Analysis of MICA rs2596542 polymorphism also yielded the same result (OR=2.90, 95%CI=1.10-7.67), as did their risk alleles. Specifically, the interaction between rs2596542 and rs2069705 polymorphisms increased the HCC risk by 1.41 times and between rs2596542 and rs2069727 polymorphisms the increased risk of HCC by 5.56 times. CONCLUSIONS IFN-γ rs2069727 and MICA rs2596542 polymorphisms may be related to the incidence of HCC. Interaction exists between the polymorphisms of IFN-γ and MICA, which may increase risk of HCC.

Significant Association Between Adiponutrin and Hepatocellular Carcinoma Risk.

ADPN I148M polymorphism has been consistently reported to play a role in liver-associated diseases, such as alcoholic liver disease, chronic hepatitis C, and liver fat and fibrosis in nonalcoholic fatty liver disease. This significant association was also indicated in a series of hepatocellular carcinoma (HCC) studies, where the significance may be affected due to the small sample sizes. The aim of this study was to reexamine the ADPN-HCC association by use of meta-analysis. Biweekly computer-based literature searches plus manual screening were undertaken in an effort to identify all studies that met the predefined inclusion criteria. The Mantel-Haenszel method was selected to estimate risk effects (odds ratio [OR] and 95% confidence interval [CI]). To examine reliability of the pooled risk effects, we additionally performed sensitivity analysis and publication bias tests. Ten studies (1335 HCC patients and 2927 HCC-free controls) were identified for the meta-analysis. We found significantly increased risk of HCC attributable to presence of ADPN I148M polymorphism, with the highest risk associated with the M/M genotype under the recessive model of inheritance (OR = 2.23, 95% CI = 1.87-2.67, between-study heterogeneity: P = 0.468). The significant increase persisted in Caucasian and African when data were stratified by ethnicity. Subgroup analysis according to source of controls revealed similar risk effects. Our meta-analysis indicates that I148M polymorphism in the ADPN gene may independently contribute to the progression of HCC irrespective of the etiologies.

Less Aggressive Surgical Procedure for Treatment of Solid Pseudopapillary Tumor: Limited Experience from a Single Institute.

OBJECTIVES: To evaluate the clinical characteristics and radiological features of solid pseudopapillary tumor (SPT) and assess surgical therapy strategy. METHODS: A retrospective review was performed in 62 patients pathologically confirmed of SPT treated between 2003 and 2014. The clinical features, radiological examinations and surgical strategies were analyzed. RESULTS: 56 females and 6 males were included in this study, mean age was 26 years old (range: 8-66 years old) with mean size of the tumor was 7.2 cm (range: 3-15 cm), and most tumor were commonly located in the head of pancreas (n = 29). Among all the cases, 3 patients had liver metastasis and underwent resection of SPT and liver metastasis. Furthermore, we performed 29 cases of local tumor excision; other patients underwent pancreaticoduodenectomy, middle pancreatectomy, middle pancreatectomy with splenectomy, distal pancreatectomy with spleen preservation, distal pancreatectomy with splenectomy and duodenum-preserving pancreatic head resection. No patient suffered from lymph node metastases. After median follow-up of 46 months (range: 2-135 months), no mortality or local recurrence or distant metastasis was found. CONCLUSIONS: Solid pseudopapillary tumor is a latent malignant tumor with excellent prognosis. If feasible, less aggressive resection without regular lymphadenectomy is recommended for treatment of patients with SPT.

Common Variants of the Prostaglandin-Endoperoxide Synthase 2 Gene and Hepatocellular Carcinoma Susceptibility.

Hepatocellular carcinoma (HCC) is a heterogeneous disease with substantial genetic constitution. Previous work has evaluated the effect of prostaglandin-endoperoxide synthase 2 (PTGS2) variants (-765G/C, -1195A/G, and +8473T/C) on the development of HCC, but the conclusions are inconsistent. We conducted a meta-analysis in this work. Data from 7 case-control studies were combined to assess the association between PTGS2 variants and HCC. The risk of HCC (OR and 95% CI) was estimated using either the fixed- or the random-effects model according to the Q test. No significant association was identified for -765G/C and +8473T/C. However, we identified a significantly decreased risk in relation to the GG genotype of -1195A/G (OR = 0.70, 95% CI = 0.50-0.98 for GG versus AA). We also observed a similar decrease (OR = 0.47, 95% CI = 0.23-0.95 for GG versus AA) in Caucasian samples. Variant -1195A/G in the promoter PTGS2 may protect against the malignant progression of HCC. This significant association suggests that -1195A/G could be used as a biomarker of HCC.

Relevance between HLA-DP gene rs2281388 polymorphism and hepatocellular carcinoma risk.

PURPOSE: We carried out this study to find out the relevance between rs2281388 T/C polymorphism of human leukocyte antigen (HLA) gene and hepatocellular carcinoma (HCC) risk in Chinese Han population. METHODS: The method of polymerase chain reaction (PCR) was applied to amplify the genomic DNA. Then the PCR products were sequenced to test the HLA-DP gene rs2281388T/C polymorphism of the case and control groups. Odds ratios (ORs) and 95% confidence interval (95% CIs) were utilized to evaluate the potential correlation between rs2281388 variants and HCC risk. RESULTS: We analyzed the rs2281388 polymorphism distribution among the clinical pathological features. The results showed that there existed a significant statistic correlation between rs2281388T/C polymorphism of HLA-DP gene and HBsAg feature, and no significant correlation was found between rs2281388 and other clinical features. Further analysis showed that the TT genotype of rs2281388 was significantly correlated with HCC risk, and the same to T allele, but there was no significant difference of CT genotype distribution in case and control groups. CONCLUSION: TT genotype and T allele of HLA-DP gene rs2281388 polymorphism may increase the risk of HCC.

Aberrant Expression of CCAT1 Regulated by c-Myc Predicts the Prognosis of Hepatocellular Carcinoma.

BACKGROUND: CCAT1 has been reported to be linked with pathogenesis of malignancies including colon cancer and gastric cancer. However, the regulatory effect of CCAT1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this research was to identify any role of CCAT1 in the progression of HCC. MATERIALS AND METHODS: Real time-PCR was performed to test the relative expression of CCAT1 in HCC tissues. A computation screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with CCAT1 promoter in vivo was tested by Pearson correlation analysis and chromatin immunoprecipitation assay. Additionally, Kaplan-Meier analysis and Cox proportional hazards analyses were performed. RESULTS: c-Myc directly binds to the E-box element in the promoter region of CCAT, and when ectopically expressed increases promoter activity and expression of CCAT1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of CCAT1 demonstrated better overall and relapse-free survival compared with the high expression group. Cox proportional hazards analyses showed that CCAT1 expression was an independent prognostic factor for HCC patients. CONCLUSIONS: The findings demonstrated CCAT1, acting as a potential biomarker in predicting the prognosis of HCC, is regulated by c-Myc.

CCAT1 promotes hepatocellular carcinoma cell proliferation and invasion.

It has been reported that CCAT1 is involved in the development of malignancies including colon cancer and gastric cancer. However, the role of CCAT1 in HCC still remains unknown. Real-time PCR was performed to test the relative expression of CCAT1 in HCC tissues and cell lines. We performed Chi-Square Analysis to study the correlation between clinical characteristics and CCAT1 expression. Based on the correlation, cell proliferation assay, cell invasion assay, wound healing assay and cell apoptosis assay were conducted in two HCC cell lines to examine the regulatory effect of CCAT1 on the HCC cells. The results indicated that the expression of CCAT1 was significantly increased in HCC tissues and cells compared with controls. We also found that the abnormally expressed CCAT1 could promote cell proliferation, migration and invasion. Taken together, our findings demonstrated that the aberrant expression of CCAT1 promotes hepatocellular carcinoma in vitro.