scholarly journals Identification of Platform-Independent Diagnostic Biomarker Panel for Hepatocellular Carcinoma using Large-scale Transcriptomics Data

2019 ◽  
Author(s):  
Harpreet Kaur ◽  
Anjali Dhall ◽  
Rajesh Kumar ◽  
Gajendra P. S. Raghava
Keyword(s):  
Hepatocellular Carcinoma ◽  
Large Scale ◽  
External Validation ◽  
Disease Free Survival ◽  
Prognostic Indicators ◽  
Support Vector ◽  
Diagnostic Biomarker ◽  
Free Survival ◽  
Biomarker Panel ◽  
Wide Range

AbstractThe high mortality rate of hepatocellular carcinoma (HCC) is primarily due to its late diagnosis. In the past numerous attempts have been made to design genetic biomarkers for the identification of HCC; unfortunately, most of the studies are based on a small dataset obtained from a specific platform or lack of their reasonable validation performance on the external datasets. In order to identify a universal expression-based diagnostic biomarker panel for HCC that can be applicable across multiple platforms; we have employed large scale transcriptomic profiling datasets containing a total of 2,306 HCC and 1,655 non-tumorous tissue samples. These samples were obtained from 29 studies generated by mainly four types of profiling techniques include Affymetrix, Illumina, Agilent and High-throughput-seq, which implemented a wide range of platforms. Firstly, we scrutinized 26 genes that are differentially expressed or regulated in uniform pattern among numerous datasets. Subsequently, we identified three genes (FCN3, CLEC1B, & PRC1) panel-based HCC biomarker using different machine learning techniques include Simple-threshold based approach, Extra Trees, Support Vector Machine, Random Forest, K Neighbors Classifier, Logistic Regression etc. Three-genes panel-based HCC biomarker classified HCC samples and non-tumorous samples of training and three external validation datasets with an accuracy between 93 to 98% and AUROC (Area Under Receiver Operating Characteristic curve) in a range of 0.97 to 1.0. Furthermore, the prognostic potential of these genes was evaluated on TCGA cohort and GSE14520 cohort using univariate survival analysis revealed that these genes are independent prognostic indicators for various types of the survivals, i.e. OS (Overall Survival), PFS (Progression-Free Survival), DFS/RFS (Disease-Free Survival/Recurrence-Free Survival) and DSS (Disease-Specific Survival) of HCC patients and significantly stratify high-risk and low-risk HCC patients (p-value <0.05). In conclusion, we identified a universal platform-independent three genes-based biomarker that can predict HCC patients with high precision; also possess significant prognostic potential. Eventually, to provide service to the scientific community, we developed a webserver HCCPred based on the above study (http://webs.iiitd.edu.in/raghava/hccpred/).

A 10-year retrospective analysis of risk factors, patterns of cancer recurrence, and survival after liver transplant for cirrhosis and hepatocellular carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4617-4617
Author(s):  
A. O. Kaseb ◽  
M. Bansal ◽  
I. Wollner ◽  
V. Shah ◽  
D. Moonka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Disease Free Survival ◽  
Small Sample ◽  
Prognostic Indicators ◽  
Term Survival ◽  
Free Survival ◽  
Pathologic Features ◽  
Disease Free

4617 Introduction: Determining eligible patients who are likely to have better outcomes following orthotopic liver transplant (OLT) for cirrhosis and hepatocellular carcinoma (HCC) is an ongoing challenge. In addition, tumor recurrence represents a major limitation of long-term survival in this setting. Patients and Methods: The study analyzed 72 OLT recipients for cirrhosis and HCC, between 1996–2006. The endpoints were frequency, patterns, localization, and risk factors of recurrence. Survival from time of OLT to recurrence was compared with primary tumor and patient characteristics, and type of treatment received pre- and post-OLT using univariate and multivariate analyses. Survival was estimated using Kaplan-Meier plots. Results: 13 recurrences (18%) occurred after a median of 33.4 months follow up (6–123 months). 11/13 (84.6%) were distant metastases. Using cox regression analysis and log-rank p-value; bilobar involvement, a tumor number of =3, tumor grade 2 or 3, size >3 cm, vascular invasion, and elevated AFP at diagnosis were all positively associated with recurrence (either distant or any). Tumors that met Milan criteria were associated with a lower likelihood of recurrence. In addition, Pre and post-OLT treatments were not found to be associated with significantly improved disease-free survival. Conclusions: Our analyses confirmed that advanced pathologic features are independently associated with significantly shorter disease-free survival. Pre- and post-OLT treatment modalities were not observed to improve disease-free survival for patients with bad prognostic indicators. However, this is limited due to our small sample size and our univariate anaylsis. We conclude that careful patient selection based on prognostic indicators would maximize benefit from use of this expensive and limited resource. [Table: see text] No significant financial relationships to disclose.

Carbohydrate Antigen 19-9 Increases the Predictive Efficiency of a-Fetoprotein for Prognosis of Resected Hepatocellular Carcinoma

2018 ◽  
Vol 84 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Li Zhou ◽  
Jing-An Rui ◽  
Shao-Bin Wang ◽  
Shu-Guang Chen ◽  
Qiang Qu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Large Scale ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Carbohydrate Antigen ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Disease Free ◽  
Predictive Efficiency

Serum α-fetoprotein (AFP) is a classical biomarker for both diagnosis and prognosis of hepatocellular carcinoma (HCC). However, its predictive efficiency for prognosis remains unsatisfactory. This study explores whether integrating AFP and carbohydrate antigen (CA) 19-9/carcinoembryonic antigen (CEA) increase its prognostic efficiency in HCC. A total of 67 HCC patients with complete record of AFP, CA19-9, and CEA, who underwent radical hepatectomy, were included. The sole and combined evaluations for prognostic significance of the three markers were performed. In the first, it was found by one-factor analysis that AFP was a univariate prognostic indicator for disease-free survival, but not overall survival, whereas CEA and CA19-9 were not statistically significant, although the latter was of marginally predictive significance for disease-free survival. Subsequently, it was revealed that combined evaluation of AFP and CA19-9, rather than AFP and CEA, distinguished overall and disease-free survival more effectively, compared with single ones. However, this combination was not significant in multivariate Cox regression analysis, thus needing further validation, especially in large-scale prospective investigations. The addition of vascular invasion to AFP/CA19-9 combination might provide enhanced predictive power for disease-free survival. Collectively, these results preliminarily suggest that CA19-9 increases the predictive efficiency of AFP for prognosis of HCC after resection.

scholarly journals Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592098707
Author(s):  
Carolina Méndez-Blanco ◽  
Paula Fernández-Palanca ◽  
Flavia Fondevila ◽  
Javier González-Gallego ◽  
José L. Mauriz
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Tumor Size ◽  
Vasculogenic Mimicry ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Hypoxia Inducible Factors ◽  
Free Survival ◽  
Node Metastasis ◽  
Clinicopathological Significance

Background: Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients. Methods: We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test. Results: HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration. Conclusions: HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.

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.

A Risk Score Model Associated with Tumor Microenvironment Predicts Disease-Free Survival After Radical Prostatectomy

2020 ◽  
Author(s):  
Hao Zhao ◽  
Xuening Zhang ◽  
Zhan Shi ◽  
Songhe Shi
Keyword(s):  
Tumor Microenvironment ◽  
Gleason Score ◽  
Risk Score ◽  
Regression Models ◽  
Cox Regression ◽  
External Validation ◽  
Disease Free Survival ◽  
Data Set ◽  
Free Survival ◽  
Disease Free

Abstract Background Tumor microenvironment (TME) and immune checkpoint inhibitors has been shown to promote active immune responses through different mechanisms. We aimed to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa).Methods The gene transcriptome profiles and clinical information of PCa patients were obtained from the TCGA database, and the immune, stromal and estimate scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of risk score (RS) model based on univariate Cox and LASSO Cox regression models analysis, and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 data set was used for external validation. Finally, 22 subsets of tumor-infiltrating immune cells (Tiics) were analyzed using the Cibersort algorithm.Results In this study, the patients with higher immune, stromal, and estimate scores were associated with poorer DFS, higher Gleason score, and higher AJCC T stage. Based on the immune and stromal scores, the Venny diagram screened out 515 cross DEGs. The univariate COX and Lasso Cox regression models were used to select 18 DEGs from 515 DEGs, and constructed a RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (P<0.001). The AUC of 1-year, 3-year and 5-year DFS rates in RS model were 0.778, 0.754 and 0.750, respectively. In addition, the RS model constructed from 18 genes was found to be more sensitive than Gleason score (1, 3, 5 year AUC= 0.704, 0.677 and 0.682). The nomograms of DFS were established based on RS and Gleason scores. The AUC of the nomograms in the first, third, and fifth years were 0.802, 0.808, and 0.796, respectively. These results have been further validated in GEO. In addition, the proportion of Tregs was higher in high-RS patients (P<0.05), and the expression of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) was higher in high-RS patients (P<0.05).Conclusion We identified 18 TME-related genes from the TCGA database, which were significantly related to DFS in PCa patients.

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