scholarly journals Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Pan ◽  
Geng-yuan Hu ◽  
Shi Jiang ◽  
Shun-jie Xia ◽  
Hendi Maher ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aerobic Glycolysis ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Sorafenib Therapy ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Advanced Stages ◽  
Disease Free

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

scholarly journals Identification of ST7 Alteration Profile, Frequency of Alteration and Correlation with ST7-Related Genes using TCGA Data

2019 ◽  
Vol 16 (3) ◽  
pp. 217-230
Author(s):  
Nurdina CHARONG ◽  
Moltira PROMKAN
Keyword(s):  
Disease Free Survival ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Stomach Adenocarcinoma ◽  
Using Data ◽  
Liver Hepatocellular Carcinoma ◽  
Disease Free ◽  
Genome Atlas

ST7 (Suppression of Tumorigenicity 7) was reported as a protein playing a role in maintaining cellular structure. This study aims to investigate the ST7 alteration profiles and frequency of alteration in different cancers using data from The Cancer Genome Atlas (TCGA). The correlation between alterations of ST7 and angiogenesis-related genes, SERPINE1, MMP13, and VEGFA, was determined and the relation between ST7 and genes involved in suppression of ST7 transcription, PRMT5 and SMARCA4, were also analyzed. Data of 6 cancer groups from The Cancer Genome Atlas (TCGA) including ovarian serous cystadenocarcinoma (OSC), liver hepatocellular carcinoma (LHC), bladder urothelial adenocarcinoma (BUA), stomach adenocarcinoma (SC), prostate adenocarcinoma (PRAD) and glioblastoma multiforme (GBM) were downloaded for this study. The results indicated that 3 alteration patterns including amplification, missense mutation, and deletion were observed in 6 cancer studies. Gene pair between ST7 and SERPINE1 indicated the co-occurrent alteration in BUC, OSC and SC (p < 0.05). However, no association between alterations of these 2 genes and survival events in our study was observed. Shorter overall survival rate and disease-free survival were found in BUC patients with ST7, PRMT5, and  SMARCA4 alterations. These findings suggest that using TCGA data can target the potential genes involved in carcinogenesis. Combining ST7 with PRMT5 and SMARCA4 could be used as indicators for analyzing the patient survival in BUC patients and may serve as the potential therapeutic target for cancer in the future.

scholarly journals HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zongguo Yang ◽  
Yunfei Lu ◽  
Qingnian Xu ◽  
Bozong Tang ◽  
Cheol-Keun Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Vascular Invasion ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Tumor Tissues ◽  
Disease Free

Objective. This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival.Methods. We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376.Results. Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797–0.983, andP=0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835–0.998, andP=0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01–1.137, andP=0.022and HR = 2.4, 95% CI = 1.092–5.273, andP=0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rankP=0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008–1.29, andP=0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523–0.803, andP<0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277–1.646, andP<0.001and OR = 1.613, 95% CI = 1.1–2.365, andP=0.014, resp.).Conclusions. Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes.

scholarly journals TP53 mutations as potential prognostic markers for specific cancers: Analysis of data from The Cancer Genome Atlas and the International Agency for Research on Cancer TP53 Database

2018 ◽  
Author(s):  
Victor Li ◽  
Karen Li ◽  
John T. Li
Keyword(s):  
Survival Time ◽  
Disease Free Survival ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
International Agency ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Cancer Genome Atlas ◽  
Disease Free ◽  
Genome Atlas

AbstractMutations in the tumor suppressor gene TP53 are associated with a variety of cancers. Therefore, it is important to know the occurrence and the prognostic effects of TP53 mutations in certain cancers. Over 29,000 cases of TP53 mutations were obtained from the April 2016 release of the Internal Agency for Research on Cancer (IARC) TP53 Database, and 7,893 cancer cases were compiled in the cBioPortal for Cancer Genomics from the 33 most recent studies of The Cancer Genome Atlas (TCGA). The data was analyzed, and it was found that the majority of TP53 mutations were missense and the major mutational hotspots were located at codons 248, 273, 175, and 245 in exons 4–8 for somatic mutations with the addition of codon 337 and other mutations in exons 9–10 for germline mutations. Out of 33 TGCA studies, the effects of TP53 mutations were statistically significant in ten cancers (ovarian serous cystadenocarcinoma, lung adenocarcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, acute myeloid leukemia, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, uterine endometrial carcinoma, and thymoma) for survival time and in six cancers (ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, hepatocellular carcinoma, chromophobe RCC, acute myeloid leukemia, and thymoma) for disease-free survival time. Also, it was found that the most common p53 mutation in hepatocellular carcinomas (R249S) was a much better indicator for poor prognosis than TP53 mutations as a whole.Author summaryThe TP53 gene codes for the tumor suppressor protein, p53, which is essential for DNA repair, cell cycle arrest, and apoptosis. It is commonly inactivated or partially disabled by mutations, contributing to the development of a variety of human cancers. In this study, over 29,000 cases from the April 2016 release of the International Agency for Research on Cancer TP53 Database (IARC) were analyzed to determine the distribution of mutations in the TP53 gene. Data was also collected from the 33 most recent The Cancer Genome Atlas (TCGA) studies to determine the prevalence of TP53 mutations in cancers and their effects on survival and disease-free survival time. It was found that there were statistically significant differences between cases with and without TP53 mutations in ten cancers when comparing survival time, and in six cancers when comparing disease-free survival time. This indicates that TP53 mutations are potential prognostic markers that can be used to further improve the accuracy of predicting the survival time and disease-free survival time of cancer patients.

scholarly journals Oncogenic Roles of RAD51AP1 in Tumor Tissues Related to Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097714
Author(s):  
Liping Zhuang ◽  
Yuan Zhang ◽  
Zhiqiang Meng ◽  
Zongguo Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Fibrosis ◽  
Vascular Invasion ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Intrahepatic Metastasis ◽  
Free Survival ◽  
Tumor Tissues ◽  
Disease Free

Objective: This study aimed to investigate the associations between RAD51AP1 and the outcomes of hepatocellular carcinoma (HCC). Methods: RAD51AP1 expression levels were compared in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset. Results: RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all P < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression ( P = 0.0034 and P = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset ( P = 0.0074 and P = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, P = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, P = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml. Conclusions: Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.

scholarly journals Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Chi Square ◽  
Tumor Tissues ◽  
The Relationship ◽  
Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

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