Value of HCC-MELD Score in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation

Context: Liver transplantation (LT) is considered the ideal therapy for patients with hepatocellular carcinoma (HCC) having cirrhosis but the shortage of liver donors and the risk of dropout from the wait list due to tumor progression severely limit transplantation. A new prognostic score, the HCC-model for end-stage liver disease (HCC-MELD), was developed by combining α-fetoprotein (AFP), MELD, and tumor size, to improve risk stratification of dropout in patients with HCC. Objectives: In this study, we investigated the ability of the HCC-MELD score in predicting the posttransplant for patients fulfilling Milan criteria (MC). Design: Two hundred patients with stage II tumor were retrospectively reviewed from a total of 1290 transplants performed at our institution from October 1997 through April 2015. Cox regression analysis was performed to identify the prognostic factors impacting the posttransplant survival. Results: Overall survival at 1, 5, and 10 years was 89.3%, 71.1%, and 67.2%, whereas disease-free survival was 86.4%, 66.5%, and 52.4%, respectively. Multivariate analysis showed HCC-MELD score (hazard ratio [HR] 39.6, P < .001) and microvascular invasion (HR 2.41, P = .002) to be independent risk factors for recurrence, whereas HCC diameter (HR 1.15, P = .041), HCC-MELD (HR 15.611, P = .006), and grading (HR 2.17, P = .03) proved to be predictive factors of poor overall survival. Conclusion: Our study showed the validity of the HCC-MELD equation in the evaluation of patients undergoing LT for HCC. This score offers a reliable method to assess the risk of waiting list dropout and predict posttransplantation outcomes.

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Indication of Liver Transplantation for Hepatocellular Carcinoma Should Be Reconsidered in Case of Microvascular Invasion and Multilocular Tumor Occurrence

Journal of Clinical Medicine ◽

10.3390/jcm10061155 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1155

Author(s):

Jan-Paul Gundlach ◽

Stephan Schmidt ◽

Alexander Bernsmeier ◽

Rainer Günther ◽

Victor Kataev ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Overall Survival ◽

Cox Regression ◽

Disease Free Survival ◽

Microvascular Invasion ◽

Simultaneous Occurrence ◽

Free Survival ◽

Cox Regression Analysis ◽

Disease Free

Liver transplantation (LT) is routinely performed for hepatocellular carcinoma (HCC) in cirrhosis without major vascular invasion. Although the adverse influence of microvascular invasion is recognized, its occurrence does not contraindicate LT. We retrospectively analyzed in our LT cohort the significance of microvascular invasion on survival and demonstrate bridging procedures. At our hospital, 346 patients were diagnosed with HCC, 171 patients were evaluated for LT, and 153 were listed at Eurotransplant during a period of 11 years. Among these, 112 patients received LT and were included in this study. Overall survival after 1, 3 and 5 years was 86.3%, 73.9%, and 67.9%, respectively. Microvascular invasion led to significantly reduced overall (p = 0.030) and disease-free survival (p = 0.002). Five-year disease-free survival with microvascular invasion was 10.5%. Multilocular tumor occurrence with simultaneous microvascular invasion revealed the worst prognosis. In our LT cohort, predominant bridging treatment was transarterial chemoembolization (TACE) and the number of TACE significantly correlated with poorer overall survival after LT (p = 0.028), which was confirmed in multiple Cox regression analysis for overall and disease-free survival (p = 0.015 and p = 0.011). Microvascular tumor invasion is significantly associated with reduced prognosis after LT, which is aggravated by simultaneous occurrence of multiple lesions. Therefore, indication strategies for LT should be reconsidered.

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Upregulated miR-16 expression is an independent indicator of relapse and poor overall survival of colorectal adenocarcinoma patients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2016-0756 ◽

2017 ◽

Vol 55 (5) ◽

Cited By ~ 12

Author(s):

Marios A. Diamantopoulos ◽

Christos K. Kontos ◽

Dimitrios Kerimis ◽

Iordanis N. Papadopoulos ◽

Andreas Scorilas

Keyword(s):

Overall Survival ◽

Cancer Progression ◽

Reverse Transcription ◽

Colorectal Adenocarcinoma ◽

Cox Regression ◽

Malignant Tumors ◽

Disease Free Survival ◽

Poor Overall Survival ◽

Cox Regression Analysis ◽

Total Rna

AbstractBackground:Colorectal adenocarcinoma is one of the most common malignant tumors of the gastrointestinal tract and the second leading cause of cancer-related deaths among adults in Western countries. miR-16 is heavily involved in cancer progression. In this study, we examined the potential diagnostic and prognostic utility of miR-16 expression in colorectal adenocarcinoma.Methods:Total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After polyadenylation of 2 μg total RNA by poly(A) polymerase and subsequent reverse transcription with an oligo-dT adapter primer, miR-16 expression was determined using an in-house developed reverse transcription quantitative real-time PCR method, based on SYBR Green chemistry.Results:miR-16 was shown to be significantly upregulated in colorectal adenocarcinoma specimens compared to non-cancerous colorectal mucosae, suggesting its potential exploitation for diagnostic purposes. Moreover, high miR-16 expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis confirmed that miR-16 overexpression is a significant unfavorable prognosticator in colorectal adenocarcinoma, independent of other established prognostic factors, radiotherapy, and chemotherapy. Interestingly, miR-16 overexpression retains its unfavorable prognostic value in patients with advanced yet locally restricted colorectal adenocarcinoma that has not grown through the wall of the colon or rectum (T3) and in those without distant metastasis (M0).Conclusions:Overexpression of the cancer-associated miR-16 predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological factors that are currently used for prognostic purposes.

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Identification of Seven-Gene Hypoxia Signature for Predicting Overall Survival of Hepatocellular Carcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.637418 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuping Bai ◽

Wenbo Qi ◽

Le Liu ◽

Jing Zhang ◽

Lan Pang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Cox Regression ◽

Risk Group ◽

Disease Free Survival ◽

High Risk Group ◽

Prognostic Models ◽

Cox Regression Analysis ◽

Significant Difference

BackgroundHepatocellular carcinoma (HCC) is ranked fifth among the most common cancer worldwide. Hypoxia can induce tumor growth, but the relationship with HCC prognosis remains unclear. Our study aims to construct a hypoxia-related multigene model to predict the prognosis of HCC.MethodsRNA-seq expression data and related clinical information were download from TCGA database and ICGC database, respectively. Univariate/multivariate Cox regression analysis was used to construct prognostic models. KM curve analysis, and ROC curve were used to evaluate the prognostic models, which were further verified in the clinical traits and ICGC database. GSEA analyzed pathway enrichment in high-risk groups. Nomogram was constructed to predict the personalized treatment of patients. Finally, real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expressions of KDELR3 and SCARB1 in normal hepatocytes and 4 HCC cells. The expressions of SCARB1 in hepatocellular carcinoma tissue in 46 patients were detected by immunohistochemistry, and the correlation between its expressions and disease free survival of patient was calculated.ResultsThrough a series of analyses, seven prognostic markers related to HCC survival were constructed. HCC patients were divided into the high and low risk group, and the results of KM curve showed that there was a significant difference between the two groups. Stratified analysis, found that there were significant differences in risk values of different ages, genders, stages and grades, which could be used as independent predictors. In addition, we assessed the risk value in the clinical traits analysis and found that it could accelerate the progression of cancer, while the results of GSEA enrichment analysis showed that the high-risk group patients were mainly distributed in the cell cycle and other pathways. Then, Nomogram was constructed to predict the overall survival of patients. Finally, RT-qPCR showed that KDELR3 and SCARB1 were highly expressed in HepG2 and L02, respectively. Results of IHC staining showed that SCARB1 was highly expressed in cancer tissues compared to adjacent normal liver tissues and its expression was related to hepatocellular carcinoma differentiation status. The Kaplan-Meier survival showed a poor percent survival in the SCARB1 high group compared to that in the SCARB1 low group.ConclusionThis study provides a potential diagnostic indicator for HCC patients, and help clinicians to deepen the comprehension in HCC pathogenesis so as to make personalized medical decisions.

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Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

10.21203/rs.3.rs-1070685/v1 ◽

2021 ◽

Author(s):

Xinxin Chen ◽

Wenxia Qiu ◽

Xuekun Xie ◽

Zefeng Chen ◽

Zhiwei Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Tumor Diameter ◽

Cox Regression Analysis ◽

Tumor Capsule ◽

Calibration Curves ◽

Solitary Hepatocellular Carcinoma

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

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Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

10.21203/rs.3.rs-125323/v1 ◽

2020 ◽

Author(s):

Ran Wei ◽

Jichuan Quan ◽

Shuofeng Li ◽

Zhao Lu ◽

Xu Guan ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

Cancer Stemness ◽

Poor Overall Survival ◽

Tissue Samples ◽

Cox Regression Analysis ◽

Rna Methylation ◽

M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

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Identification of a five-gene signature in association with overall survival for hepatocellular carcinoma

PeerJ ◽

10.7717/peerj.11273 ◽

2021 ◽

Vol 9 ◽

pp. e11273

Author(s):

Lei Yang ◽

Weilong Yin ◽

Xuechen Liu ◽

Fangcun Li ◽

Li Ma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Overall Survival ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Signature ◽

Gene Set Enrichment Analysis ◽

Enrichment Score ◽

Hub Genes ◽

Cox Regression Analysis

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.

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Surgical Resection Significantly Promotes the Overall Survival of Patients with Hepatocellular Carcinoma: A Propensity Score Matching Analysis

10.21203/rs.3.rs-148506/v1 ◽

2021 ◽

Author(s):

Pei-Min Hsieh ◽

Hung-Yu Lin ◽

Chao-Ming Hung ◽

Gin-Ho Lo ◽

I-Cheng Lu ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Overall Survival ◽

Propensity Score ◽

Propensity Score Matching ◽

Surgical Resection ◽

Cox Regression ◽

Survival Rates ◽

Hbv Infection ◽

Cox Regression Analysis

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

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Identification of a Liver Progenitor Cell-Related Genes Signature Predicting Overall Survival for Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211041425 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110414

Author(s):

Xiaoyong Li ◽

Jiaqong Lin ◽

Yuguo pan ◽

Peng Cui ◽

Jintang Xia

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Regression Analysis ◽

Prognostic Model ◽

Cox Regression ◽

Risk Group ◽

Gene Signature ◽

Regression Analyses ◽

Related Gene ◽

Cox Regression Analysis

Background: Liver progenitor cells (LPCs) play significant roles in the development and progression of hepatocellular carcinoma (HCC). However, no studies on the value of LPC-related genes for evaluating HCC prognosis exist. We developed a gene signature of LPC-related genes for prognostication in HCC. Methods: To identify LPC-related genes, we analyzed mRNA expression arrays from a dataset (GSE57812 & GSE 37071) containing LPCs, mature hepatocytes, and embryonic stem cell samples. HCC RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to explore the differentially expressed genes (DEGs) related to prognosis through DEG analysis and univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed to construct the LPC-related gene prognostic model in the TCGA training dataset. This model was validated in the TCGA testing set and an external dataset (International Cancer Genome Consortium [ICGC] dataset). Finally, we investigated the relationship between this prognostic model with tumor-node-metastasis stage, tumor grade, and vascular invasion of HCC. Results: Overall, 1770 genes were identified as LPC-related genes, of which 92 genes were identified as DEGs in HCC tissues compared with normal tissues. Furthermore, we randomly assigned patients from the TCGA dataset to the training and testing cohorts. Twenty-six DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed in the TCGA training set, and a 3-gene signature was constructed to stratify patients into 2 risk groups: high-risk and low-risk. Patients in the high-risk group had significantly lower OS than those in the low-risk group. Receiver operating characteristic curve analysis confirmed the signature's predictive capacity. Moreover, the risk score was confirmed to be an independent predictor for patients with HCC. Conclusion: We demonstrated that the LPC-related gene signature can be used for prognostication in HCC. Thus, targeting LPCs may serve as a therapeutic alternative for HCC.

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Establishment and Validation of an MTORC1 Signaling-Related Gene Signature to Predict Overall Survival in Patients with Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/6299472 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Zheng Yao ◽

Song Wen ◽

Jun Luo ◽

Weiyuan Hao ◽

Weiren Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Decision Tree ◽

Survival Data ◽

Cox Regression ◽

Gene Signature ◽

Related Gene ◽

Cox Regression Analysis ◽

Cancer Hallmarks ◽

Mtorc1 Signaling

Background. Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. Methods. The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. Results. Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. Conclusions. The present study may contribute to the improvement of current prognostic systems for patients with HCC.

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Opposite roles of BAP1 in overall survival of uveal melanoma and cutaneous melanoma

10.21203/rs.2.15589/v1 ◽

2019 ◽

Author(s):

Feng Liu-Smith

Keyword(s):

Overall Survival ◽

Uveal Melanoma ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Survival Function ◽

Poor Overall Survival ◽

Cox Regression Analysis ◽

Oncogenic Pathways ◽

Cellular Context ◽

Age Of Diagnosis

Abstract Background: BAP1 germline mutations predispose individuals to a number of cancer types including uveal melanoma (UM) and cutaneous melanoma (CM) which are distinctively different in the oncogenic pathways. BAP1 loss was common in UM and was associated with a worse prognosis. BAP1 loss was rare in CM and the outcome was unclear. Methods: This study used TCGA UM and CM databases for survival analysis for patients with different BAP1 status and mRNA expression levels. Cox regression model was used for adjusting to known prognosis factors. Results: BAP1- (loss or low expression) predicted a poor overall survival in UM (Cox HR = 0.062, logrank p =0.007) but a contrasting better overall survival in CM (HR = 1.69, p =0.009). Multi-covariate Cox regression analysis indicated BAP1 was a significant predictor for overall survival after adjusting for age of diagnosis, presence of ulceration, Breslow depth and CM stages in patients older than 50 years but not in younger patients. Co-expression analysis revealed no shared genes in BAP1 altered UM and CM tumors, further supporting a completely distinctive role of BAP1 in CM and UM. Conclusions: low BAP1 mRNA was significantly associated with a better overall survival in CM patients, in sharp contrast to its tumor suppressor role in UM where low or loss of BAP1 indicated a worse overall survival. Function of BAP1 may be dependent on cellular context.

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