Association between HMGA1 and immunosuppression in hepatocellular carcinoma: A comprehensive bioinformatics analysis

The high mobility group A1 (HMGA1) gene is overexpressed in malignant tumors, and its expression level correlates with the progression and metastasis of tumors. However, the specific role of HMGA1 in hepatocellular carcinoma (HCC) and relevant influencing approaches in tumor immunity remain unclear. In this study, the expression and clinical significance of HMGA1 in HCC immunity were analyzed. The expression levels of HMGA1 mRNA and protein in HCC tissue and normal liver tissue were analyzed based on the cancer genome atlas, the gene expression omnibus and the Human Protein Atlas databases. The correlation between HMGA1 and clinicopathological factors was analyzed, and survival was estimated based on the expression of HMGA1. Gene set cancer analysis and the TISIDB database were used to identify tumor-infiltrating immune cells and immune inhibitors. Gene set enrichment analysis was performed to determine the involved signaling pathway. The HMGA1 genetic alterations were identified with the cBioPortal for Cancer Genomics. The expression of HMGA1 mRNA and protein was significantly higher in HCC tissue and negatively correlated with survival. Neutrophils, Th17 cells, several immune inhibitors, and signaling pathways were positively correlated with the expression of HMGA1. Amplification was the main type of genetic alteration in HMGA1. These findings demonstrate that HMGA1 can be a therapeutic target and a potential biomarker to predict the prognosis of patients with HCC. HMGA1 may affect the progression of HCC by suppressing the immune function of these patients.     

肝细胞癌诊断标志物的研究进展

肿瘤标志物,又称为生物标志物,主要由肿瘤或宿主产生,能在体液或组织中检测到并有助于诊断和鉴别肿瘤。通过测定其存在或含量可辅助肿瘤的早期诊断、分子分型、分析病程、指导治疗、监测复发或转移及判断预后等。理想的标志物一般应敏感性高,能早期测出所有肿瘤患者,同时可用于以下一种或多种情况：早期诊断;筛检高危人群;监测病程进展与疗效、早期复发和转移或指导化学治疗的终点时间。     

肝细胞癌肿瘤标志物的研究进展

肿瘤标志物检测是目前协助诊断、监测肝细胞癌(HCC)及评估预后的重要方法之一。总结了肿瘤标志物对HCC的诊断、预测肿瘤生物学特性及预后等方面的价值,以及多项肿瘤标志物联合诊断的价值。新的肿瘤标志物不断被发现,有助于提高HCC的早期诊断率和评估治疗效果。     

代谢组学在肝细胞癌标志物研究中的应用

代谢组学技术作为一种新的组学研究手段,能够揭示肝细胞癌(HCC)发生发展过程中的代谢谱差异,成为HCC生物标志物研究的热点。简述了代谢组学在HCC诊断中的意义,概括了HCC相关的生物标志物的代谢组学研究,这些研究主要以血清、尿液及肝组织代谢物为对象,通过动物实验和临床研究两个方面进行。指出分析和监视HCC发生发展过程中相应代谢物的变化,对于患者的个体化治疗具有重要价值。     

Tumour staging, morphology and p53 overexpression concur in predicting survival in hepatocellular carcinoma

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) on cirrhosis is hard to predict as it depends on tumour stage, underlying liver disease, type of treatment and, possibly, biological factors of the tumour itself. METHODS: We prospectively evaluated the survival of 91 consecutive patients with HCC on cirrhosis, diagnosed between January 1998 and December 1999. Clinical features and histological/biological aspects, including histotype, grade, p53 overexpression, cytoproliferation and apoptotic markers were analysed. RESULTS: Child-Pugh (P = 0.01), Okuda (P < 0.0001), Cancer of the Liver Italian Program (CLIP) staging (P < 0.0001) and type of treatment (P = 0.0001) were significantly related to survival. In the Cox model, CLIP staging was included as independent predictor of survival at step 1 (P < 0.0001) with Okuda at step 2 (P = 0.013). Amongst the biological factors, p53 overexpression and histotype were significantly related with survival (P = 0.0044 and 0.017 respectively). When clinical and biological variables were examined together in the Cox model, CLIP and Okuda were confirmed as being statistically related with survival (P < 0.0001 and =0.012) followed by histotype and p53 overexpression (P = 0.019 and 0.02). CONCLUSIONS: CLIP, Okuda, histotype and p53 overexpression are the strongest predictors of survival in this series of patients. These data confirm that staging of the tumour and underlying liver disease are strictly related to prognosis but support the concurrent role of clinical and biological factors in upgrading our capacity of predicting the fate of HCC patients.     

Identification of G6PC as a potential prognostic biomarker in hepatocellular carcinoma based on bioinformatics analysis

Hepatocellular carcinoma (HCC) has high mortality and incidence rates around the world with limited therapeutic options. There is an urgent need for identification of novel therapeutic targets and biomarkers for early diagnosis and predicting patient survival with HCC.Several studies ({"type":"entrez-geo","attrs":{"text":"GSE102083","term_id":"102083"}}GSE102083, {"type":"entrez-geo","attrs":{"text":"GSE29722","term_id":"29722"}}GSE29722, {"type":"entrez-geo","attrs":{"text":"GSE101685","term_id":"101685"}}GSE101685, and {"type":"entrez-geo","attrs":{"text":"GSE112790","term_id":"112790"}}GSE112790) from the GEO database in HCC were screened and analyzed by GEO2R, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted with the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interaction network was plotted and the module analysis was performed using Search Tool for the Retrieval of Inter-acting Genes/Proteins database and Cytoscape. The expression and survival of key genes were identified using UALCAN, Kaplan–Meier Plotter and ONCOMINE online databases, and the immune infiltration level of key genes was analyzed via the Tumor Immune Estimation Resource (TIMER) database.Through database analysis, eight key genes were finally screened out, and the expressions of cyclin-dependent kinase regulatory subunit 2 and glucose-6-phosphatase catalytic (G6PC), which were closely related to the survival of HCC patients, was detected by using UALCAN. Further analysis on the differential expression of G6PC in multiple cancerous tumors and normal tissues revealed low expression in many solid tumors by Oncomine and TIMER. In addition, Kaplan–Meier plotter and UALCAN database analysis to access diseases prognosis suggested that low expression of G6PC was significantly associated with poor overall survival in HCC patients. Finally, TIMER database analysis showed a significant negative correlation between G6PC and infiltration levels of six kinds of immune cells. The somatic copy number alterations of G6PC were associated with B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, dentritic cells and neutrophils.These bioinformatic data identified G6PC as a potential key gene in the diagnosis and prognosis of HCC.     

肝细胞癌早期诊断血清学标志物的研究进展

肝细胞癌(HCC)是一种发生率和致死率均较高的严重威胁人类健康的疾病。目前尚无一种血清学指标可以单独早期诊断HCC。总结了近年发现对HCC早期诊断有潜在价值的血清学标志物,并对其在诊断HCC的敏感性和特异性以及判断疾病进展等方面进行阐述,认为对HCC早期诊断应通过联合其他血清学标志物以弥补甲胎蛋白在敏感性方面的不足。     

肝细胞肝癌组织中CD90表达变化及意义

目的观察肝细胞肝癌(HCC)组织中肿瘤干细胞标记物CD90的表达变化,并探讨其临床意义。方法采用免疫组化法检测60例HCC组织(HCC组)、60例癌旁组织(癌旁组)及60例正常肝脏组织(对照组)中的CD90,分析其表达与HCC临床病理参数的关系。结果 CD90阳性表达率HCC组为76.7%(46/60)、癌旁组为48.3%(29/60)、对照组为0,3组组间两两比较,P均<0.01。CD90表达与HCC患者的性别、民族、有无门静脉瘤栓、包膜是否完整、TMN分期、病理分级有关(P均≤0.05),与HCC患者的年龄、肿瘤大小、甲胎蛋白高低、乙肝病毒是否阳性无关(P均>0.05)。结论 CD90在HCC组织及癌旁组织中高表达,HCC组织中表达更高;癌组织中CD90表达有助于HCC患者预后的判断,可为患者进行个体化诊断治疗提供参考。     

The analysis of tumor-infiltrating immune cell and ceRNA networks in laryngeal squamous cell carcinoma

Background:Laryngeal squamous cell carcinoma (LSCC) is one of the most common forms of head and neck cancers. However, few studies have focused on the correlation between competing endogenous RNA (ceRNAs) and immune cells in LSCC.Methods:RNAseq expression of LSCC and adjacent tissues were downloaded from The Cancer Genome Atlas to establish a ceRNA network. The key gene in ceRNA was screened by the cox regression analysis to establish a prognostic risk assessment model. The CIBERSORT algorithm was then used to screen important tumor-infiltrating cells related to LSCC. Finally, co-expression analysis was applied to explore the relationship between key genes in the ceRNA network and tumor-infiltrating cells. The external datasets were used to validate critical biomarkers.Results:We constructed a prognostic risk assessment model of key genes in the ceRNA network. As it turned out, Kaplan–Meier survival analysis showed significant differences in overall survival rates between high-risk and low-risk groups (P < .001). The survival rate of the high-risk group was drastically lower than that of the low-risk group, and the AUC of 1 year, 3 years, and 5 years were all above 0.7. In addition, some immune infiltrating cells were also found to be related to LSCC. In the co-expression analysis, there is a negative correlation between plasma cells and TUBB3 (r = −0.33, P = .0013). External dataset validation also supports this result.Conclusion:In this study, we found that some key genes (SLC35C1, CLDN23, HOXB7, STC2, TMEM158, TNFRSF4, TUBB3) and immune cells (plasma cells) may correspond to the prognosis of LSCC.     

Survival analysis of 904 patients with hepatocellular carcinoma in a hepatitis B virus-endemic area

Background and Aim: To investigate the clinical characteristics and survival outcomes of a large cohort of hepatocellular carcinoma (HCC) patients treated at a single institute in a hepatitis B virus (HBV)–endemic area. Methods: Between 2000 and 2003, 904 patients with HCC treated at our institute were enrolled, and followed until 2005. Results: The mean age of the patients was 56 years and 76.3% were HBV‐positive. The 1‐, 2‐, 3‐, and 4‐year survival rates were 53.8%, 40.0%, 31.4%, and 25.7%, respectively. The 4‐year survival rates for Child–Pugh class A patients treated by resection or transarterial chemoembolization (TACE) were 77.3% and 63.2% for those with modified International Union Against Cancer (UICC) stage I or II disease (P = 0.043), and 58.6% and 19.2% for those with modified UICC stage III disease (P < 0.001). In patients with Child–Pugh class A and stage IVa, the median survival times differed between TACE and chemotherapy treatments (6.9 vs 4.0 months, P = 0.003), whereas in patients with stage IVb there was no difference between treatments (8.5 vs 6.1 months, P = 0.173) Serum α‐fetoprotein level, presence of portal vein tumor thrombosis, Child–Pugh class, tumor, node, and metastasis stage, and the number and type of HCC were all related to prognosis. Significant differences in survival curves were observed among the Japanese Integrated Staging scores. Conclusions: The results of this study will be helpful in determining the survival outcomes and treatment strategies for HCC patients in HBV‐endemic areas.     

Integrated analysis of lncRNA-associated ceRNA network in p16-positive and p16-negative head and neck squamous cell carcinoma

Determination of human papillomavirus (HPV) status has become clinically relevant for head and neck squamous cell carcinoma (HNSCC) patients. p16 immunohistochemistry is one of the recommended methods for classifying HPV status. However, long noncoding RNAs (lncRNAs) and related competing endogenous RNA (ceRNA) networks linked to different p16-status HNSCC are still absent.In the present study, The Cancer Genome Atlas database provided RNA profiles as well as clinical information from 26 p16-positive HNSCC samples, 71 p16-negative HNSCC samples, and 44 adjacent normal control samples. Differentially expressed RNAs (DERNAs) between HNSCC samples and normal samples were identified by limma package in R. Functional enrichment analysis of differentially expressed mRNAs was performed using Clusterprofiler package in R. Survival analysis of DERNAs was carried out by survival package in R. The ceRNA network was constructed using GDCRNATools package in R.A total of 102 lncRNAs, 196 microRNAs (miRNAs), and 2282 mRNAs were identified as p16-positive-specific DERNAs. There were 90 lncRNAs, 153 miRNAs, and 2038 mRNAs were identified as p16-negative-specific DERNAs. Functional enrichment analysis revealed that the differentially expressed mRNAs in the p16-positive and the p16-negative group were mainly enriched in the “DNA replication” and “extracellular matrix -receptor interaction” pathway, respectively. Among the top 25 DERNAs, there were 1 key lncRNA, 1 key miRNA, and 1 key messenger RNA in the p16-positive group and 2 key lncRNAs, 1 key miRNA, and 2 key mRNAs in the p16-negative group were significantly related to the overall survival. Then the ceRNA network in the p16-positive and p16-negative group was constructed. There were 5 lncRNAs, 16 miRNAs, and 66 mRNAs included in the p16-positive group ceRNA network and 1 lncRNA, 4 miRNAs, and 28 mRNAs included in the p16-negative group ceRNA network. Among the RNAs in the ceRNA network, 5 mRNAs were significantly related to the overall survival.Taken together, we revealed the differential RNA expression profiling and the differential ceRNA network in the p16-positive and p16-negative group of HNSCC. Our findings provided a novel insight into this HPV-related cancer and potential biomarkers and therapeutic targets for HNSCC based on p16 status.     

Review of current staging systems for hepatocellular carcinoma

Several staging systems have been developed to classify patients with hepatocellular carcinoma (HCC), however, there is no consensus on which of these is the most useful and reliable. In this review article, currently available integrated staging systems taking into account both liver function and tumor progression are presented, and their characteristics and applicability for current HCC patients, many of whom are diagnosed in the early stage of the disease and treated by curative therapy, are discussed. Based on the original andsubsequent validation studies of these staging systems, we recommend that further validation studies of staging systems for HCC should focus on the revised Barcelona Clinic Liver Cancer (BCLC) staging classification, Japan Integrated Staging (JIS) score and Tokyo score.     

Identification of hub genes and candidate drugs in hepatocellular carcinoma by integrated bioinformatics analysis

Background:Hepatocellular carcinoma (HCC) is the third cancer-related cause of death in the world. Until now, the involved mechanisms during the development of HCC are largely unknown. This study aims to explore the driven genes and potential drugs in HCC.Methods:Three mRNA expression datasets were used to analyze the differentially expressed genes (DEGs) in HCC. The bioinformatics approaches include identification of DEGs and hub genes, Gene Ontology terms analysis and Kyoto encyclopedia of genes and genomes enrichment analysis, construction of protein–protein interaction network. The expression levels of hub genes were validated based on The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, and the Human Protein Atlas. Moreover, overall survival and disease-free survival analysis of HCC patients were further conducted by Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis. DGIdb database was performed to search the candidate drugs for HCC.Results:A total of 197 DEGs were identified. The protein–protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes software, 10 genes were selected by Cytoscape plugin cytoHubba and served as hub genes. These 10 genes were all closely related to the survival of HCC patients. DGIdb database predicted 29 small molecules as the possible drugs for treating HCC.Conclusion:Our study provides some new insights into HCC pathogenesis and treatments. The candidate drugs may improve the efficiency of HCC therapy in the future.     

Comparison of staging systems to predict survival in hepatocellular carcinoma.

PURPOSE: Some new staging systems in hepatocellular carcinoma (HCC) have been described in the last years. The aim of this study was to compare the survival-predicting capacity of some variables and the prognostic classifications. METHODS: Demographic, clinical, analytical variables and tumour characteristics were collected in a study including 115 patients with HCC. Predictors of survival were identified using the Kaplan-Meier test and the Cox model. Comparison between different staging systems was carried out. RESULTS: The 1-, 2- and 3-year estimated survival was 65%, 45% and 30%, respectively. Child-Pugh score and alpha-fetoprotein level greater than 400 UI/l were independent predictors of survival in the Cox model. Although all systems correctly differentiated between patients regarding survival (Kaplan-Meier, log rank < 0.05 for all), the Barcelona Clinic Liver Cancer (BCLC) showed a better discriminatory ability than the other evaluated scores. In addition, the independent homogenizing ability and stratification value of BCLC was better than that of other systems. On the contrary, model for end-stage liver disease (MELD) showed the worst results. CONCLUSIONS: Child-Pugh score and alpha-fetoprotein levels were the only independent predictors of survival in patients with HCC. Child-Pugh score showed a better prediction value for survival when compared with MELD. BCLC is more accurate than the other prognostic models evaluated in this investigation.     

Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies

Background: Although there are many studies of the predictors of death in hepatocellular carcinoma (HCC), most combine patients with and without cirrhosis and many combine those with compensated and decompensated cirrhosis. Objective: To perform a systematic review of the literature evaluating the predictors of death in patients with cirrhosis and HCC and to evaluate whether the predictors differ between patients with compensated and decompensated cirrhosis. Methods: Inclusion criteria: (i) publication in English, (ii) adult patients, (c) >80% of the patients had cirrhosis, (iv) follow‐up >6 months and (v) multivariable analysis. Quality was based on the accepted quality criteria for prognostic studies. Results: Of the 1106 references obtained, 947 were excluded because they did not meet the inclusion criteria. A total of 23 968 patients were included in 72 studies (median, 177/study); 77% male, median age 64, 55% Child–Pugh class A. The most robust predictors of death were portal vein thrombosis, tumour size, α‐foetoprotein and Child–Pugh class. Sensitivity analysis using only 15 ‘good’ studies and 22 studies in which all patients had cirrhosis yielded the same variables. In the studies including mostly compensated or decompensated patients, the predictors were both liver and tumour related. However, these studies were few and the results were not robust. Conclusions: This systematic review of 72 studies shows that the most robust predictors of death in patients with cirrhosis and HCC are tumour related and liver related. Future prognostic studies should include these predictors and should be performed in specific patient populations to determine whether specific prognostic indicators are more relevant at different stages of cirrhosis.     

Expression of HLA-G in patients with hepatocellular carcinoma

BACKGROUND:Human leukocyte antigen G(HLA-G)is a non-classical major histocompatibility complex class I molecule that has multiple immune regulatory functions including the induction of immune tolerance.The detection of HLA-G expression might serve as a clinical marker in the prediction of clinical outcomes for certain types of carcinoma.Currently, we investigated whether or not HLA-G is also expressed in patients with hepatocellular carcinoma(HCC),and whether the expression has clinical value. METHODS:Serum...     

Analysis of factors affecting long-term survival of patients with hepatocellular carcinoma following hepatectomy

The survival of 200 patients (172 males, 28 females; mean age ± SD: 53.6 ± 12 years) who underwent hepatectomy for hepatocellular carcinoma (HCC) was analyzed retrospectively to identify prognostic determinants to guide patient selection for appropriate treatment. All patients studied had had complete macroscopic extirpation of their tumor, histologic information regarding their lesions and the adjacent non-tumorous liver parenchyma, and no evidence of residual or recurrent disease 30 days after surgery. Survival was analyzed with reference to 25 different clinical (n=7), serological (n=2), macroscopic (n=4), and histological (n=12) features of the resected specimens, by using multivariate analysis. Recurrent HCC was detected in 138 patients within a median follow-up period of 12.6 months. While 33 patients had extra-hepatic disease alone, in 74, the recurrence was confined to the hepatic remnant. Survival at 1, 3, and 5 years was 58%, 34%, and 26%, respectively. The presence of residual histologic disease at the resection margin was found to be the only important prognostic determinant (P < 0.02). The distance of the macroscopic resection margin, either at 1 or 2 cm, made no difference to the long-term outcome of our patients. Following hepatectomy, a detailed pathologic examination of the resected liver specimen is mandatory to verify the status of disease clearance, as the distance of the gross surgical margin is an unreliable index.