Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common cause of cancer mortality worldwide. However, the exact molecular mechanism of HCC remains uncertain. Many enzymes are involved in one-carbon metabolism (OCM), and single nucleotide polymorphisms (SNPs) in the corresponding genes may play a role in liver carcinogenesis. In this study, we enrolled 1500 HCC patients and 1500 cancer-free controls, which were frequency-matched by age, gender, and HBV infection status. Then eight SNPs from seven OCM genes (MTHFR, MTR, MTRR, FTHFD, GART, SHMT, and CBS) were evaluated. Results showed that six SNPs (MTHFR rs1801133, MTRR rs2287780, MTRR rs10380, FTHFD rs1127717, GART rs8971, and SHMT rs1979277) were significantly associated with HCC risk in Chinese population, with P values range from 2.26 × 10(-4) to 0.035). The most significant association was detected for GART rs8971. Compared with individuals with the TT genotype, the age- and sex-adjusted odds ratio (OR) for developing HCC was 1.44 (95% confidence interval (CI): 1.03-2.02) among those with the CC genotype and 1.30 (95% CI: 1.10-1.53) for those with CT genotype. Under the log-additive model, each additional copy of minor allele C was associated with a 1.28-fold increased risk of HCC (OR = 1.28, 95% CI: 1.12-1.45). These findings indicated that genetic variants in OCM genes might contribute to HCC susceptibility.
BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two ...
Cholangiocarcinoma (CCA) is a malignant tumor with poor prognosis and high recurrence rate.There is no standard treatment for advanced CCA beyond first-line chemotherapy, which provides only limited benefits. In this study, we report a case of a postoperative recurrence ECC patient harboring a breast cancer 2 (BRCA2)-inactivating rearrangement mutation that had an obvious reaction to olaparib therapy.The patient was a 68-year-old man with postoperative recurrence of extrahepatic CCA (ECC) who declined systemic chemotherapy. In August 2015, abdominal computed tomography (CT) of the patient revealed intrahepatic bile duct dilatation, obstruction at the hepatic hilar region proximal to the common hepatic duct, and splenomegaly, and radical surgical resection was performed. Postoperative histopathology diagnosis was ECC without metastases. In February 2017, abdominal CT revealed local recurrence, and the patient refused chemotherapy. BRCA2 rearrangement were detected by next-generation sequencing. Oral administration of olaparib was initiated. The patient achieved stable disease 1 month later, progression-free survival for >10 months without any significant adverse reactions, and an overall survival (OS) of 27 months. This is the first report demonstrating the clinical benefits of olaparib in a BRCA2 rearrangement-harboring patient with ECC. This observation would help determine the best treatment option for advanced ECC patients.
Changes in the methylation levels of tumor suppressor genes or proto-oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection-induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression profile (GSE19665 and GSE62232) and methylation profile (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein-protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identified. These genes were enriched in the Gene Ontology biological processes terms of ‘inflammatory response’ [Fos proto-oncogene, AP-1 transcription factor subunit (FOS)] and ‘cell cycle process’ [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV-positive HCC.
BACKGROUND Colorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time. AIM To explore the prognostic factors and treatments of liver metastases of CRC. METHODS A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis. RESULTS The median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo ( P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) ( P < 0.05). CONCLUSION Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.
Background Hepatitis C virus (HCV) infection is a main contribution to the increase in hepatocellular carcinoma (HCC) incidence and patients’ death recently, but prognostic biomarkers for HCV-related HCC remain rarely reported. This study was to identify an lncRNA prognostic signature for HCV-HCC patients and explore their underlying function mechanisms. Methods In total, 102 HCV-HCC samples and 50 normal control samples were obtained from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis were conducted to screen an lncRNA signature that could predict overall survival (OS) and then, the risk score was calculated using this signature. The prognostic potential of this risk score was evaluated by drawing Kaplan-Meier, receiver operating characteristic (ROC) curves and performing multivariate Cox regression analyses with clinical variables. Furthermore, a co-expression and competing endogenous RNA (ceRNA) networks were constructed to explore the functional mechanisms of lncRNAs. Results Multivariate Cox regression showed six lncRNAs (SLC16A1-AS1, ZFPM2-AS1, JARID2-AS1, LINC01426, USP3-AS1 and LYPLAL1-AS1) were significantly associated with OS of HCV-HCC patients. These six lncRNAs were used to establish a risk score model, which displayed a higher prognosis prediction accuracy [area under the ROC curve (AUC) = 0.95 for training set; AUC = 0.885 for testing; AUC = 0.907 for entire set]. Also, this was independent of various clinical variables. The crucial co-expression (LINC01426/SLC16A1-AS1-AURKA/SFN/CCNB1, ZFPM2-AS1/LYPLAL1-AS1/JARID2-AS1-TSSK6) or ceRNA (USP3-AS1-hsa-miR-383-SFN) interaction axes were identified. Conclusion Our study identified a novel six-lncRNA prognosis signature for HCV-HCC patients and indicated their underlying mechanisms for HCC progression.
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