AST-to-APOA ratio to predict overall survival in hepatocellular carcinoma receiving TACE.

e16637 Background: Current guidelines lack definitive evidences about the predictive capability of clinical parameters for transcatheter arterial chemoembolization (TACE). The aim of this study was to comprehensively investigate the predictive factor among stage I-IV liver hepatocellular carcinoma (LIHC) patients after TACE. Methods: We investigated the clinical features of 211 stage I-IV patients with LIHC in discover group and 341 patients in validation group. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test. Results: Univariate Cox regression revealed that Monocyte count, TNM stage and AST-to-APOA ratio (AAR) were associated with unfavorable OS. AAR was identified as an independent predictor of OS using multivariate analysis. Kaplan-Meier curve demonstrated that patients with AAR < 50 displayed better prognosis. The median follow-up time was 17.1 (95%CI, 14.4 to 19.3) months, 3-year overall survival was 55.9% in the low AAR group versus 28.6% in the high AAR group, and there was significant difference in OS (Hazard ratio [HR] 0.47, 95%CI 0.33 to 0.67, P < 0.001). The AAR showed predictive ability for OS (12-month, AUC = 0.707). These findings were successfully validated in validation group (HR 0.62, 95%CI 0.46 to 0.84, P = 0.002; 12-month AUC = 0.636). Conclusions: AAR was an independent predictor among LIHC patients after TACE. Patients with lower AAR were optimal candidates for TACE.

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Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2019/9691067 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Hai-Ge Zhang ◽

Ping Yang ◽

Tao Jiang ◽

Jian-Ying Zhang ◽

Xue-Juan Jin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

External Beam Radiation ◽

Rank Test ◽

Beam Radiation ◽

Kaplan Meier ◽

Target Volumes ◽

The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

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Nomograms Predicting Long-Term Overall Survival and Cancer-Specific Survival in Metastatic Hepatocellular Carcinoma Patients

10.21203/rs.3.rs-31444/v1 ◽

2020 ◽

Author(s):

Chi Cui ◽

Yaru Duan ◽

Rui Li ◽

Hua Ye ◽

Peng Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

Training Group ◽

Clinicopathological Characteristics ◽

Validation Group ◽

Cancer Specific Survival ◽

Term Survival ◽

Metastatic Hepatocellular Carcinoma

Abstract Background This study aims to evaluate the clinicopathological characteristics of metastatic hepatocellular carcinoma (HCC) patients and develop nomograms to predict their long-term overall survival (OS) and cancer-specific survival (CSS). Methods Information on metastatic HCC from 2010 to 2015 was retrieved from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. The metastatic HCC patients were divided into a long-term survival (LTS) group and a short-term survival (STS) group with 1 year selected as the cut-off value. Then, we compared the demographic and clinicopathological features between the two groups. Next, all patients were randomly divided into a training group and validation group at a 7:3 ratio. Univariate and multivariate Cox regression analyses were used to identify potential predictors for OS and CSS in the training group, and nomograms of OS and CSS were established. These predictive models were further validated in the validation group. Results A total of 2163 patients were included in the current study according to the inclusion and exclusion criteria. Patients with characteristics including lower T stage and N stage; treatment with surgery, radiation or chemotherapy; no lung metastasis; and AFP negative status showed better survival. The concordance index (C-index) of the OS nomogram was 0.72 based on 9 variables. The C-index of the CSS nomogram was 0.71 based on 8 variables. Conclusions These nomograms may help clinicians make better treatment recommendations for metastatic HCC patients.

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

10.21203/rs.3.rs-121134/v1 ◽

2020 ◽

Author(s):

YuPing Bai ◽

Wenbo Qi ◽

Le Liu ◽

Jing Zhang ◽

Lan Pang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Cox Regression ◽

Risk Group ◽

Enrichment Analysis ◽

High Risk Group ◽

Prognostic Models ◽

Cox Regression Analysis ◽

Significant Difference

Abstract Background: Hepatocellular carcinoma 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. Methods: RNA-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 hepatocellular carcinoma cells. Results: Through a series of analyses, 7 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. Conclusion: This 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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Stage I ovarian immature teratomas: Is there a role for chemotherapy?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5523 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5523-5523

Author(s):

John K. Chan ◽

Emily B Rosenfeld ◽

Austin Blake Gardner ◽

Lejla Delic ◽

Daniel Stuart Kapp

Keyword(s):

Overall Survival ◽

Regression Models ◽

Cox Regression ◽

Racial Group ◽

Stage I ◽

National Cancer Database ◽

Fertility Sparing Surgery ◽

Kaplan Meier ◽

Fertility Sparing ◽

The Impact

5523 Background: To determine the impact of chemotherapy on survival of patients with stage I ovarian immature teratomas. Methods: Data obtained from the National Cancer Database from 2004-2013. Kaplan-Meier methods and multivariate Cox regression models were used for statistical analyses. Results: Of 888 patients (median age 24 years), 76%, 7%, 15%, 3% were stages I, II, III, and IV, respectively. 27%, 28%, 38%, and 8% had grades 1, 2, 3 and 4. The predominant racial group was White (50%) and remainder Black (19%), Hispanic (16%), Asian (6%) and other (9%). 64% had fertility sparing surgery and 55% received chemotherapy. For all patients, 5 year survival was over 90%. Chemotherapy did not change the 5 year survival for stage I or stage II disease (p = 0.35 and p = 0.69, respectively). However, chemotherapy improved 5 year survival from 59% to 76% in stages III-IV (p < 0.01). When controlling for other factors, older age (HR 3.2, p < 0.01), stages II and III-IV (HR 6.0, p < 0.01; HR 10.6, p < 0.01) and grades 3-4 (HR 15.3, p < 0.01) had worse survival. In a subset analysis of stage I patients chemotherapy did not improve 5 year survival of those with stage I grade 1 (p = 0.75) but chemotherapy did improved the survival of those with stage I grade 2 disease from 85% to 99% (p = 0.04). Conclusions: The overall survival of patients with immature teratomas is excellent. In patients with stage I grade 2 or higher disease chemotherapy was associated with an improved overall survival.

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Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2016/8201642 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Weijie Ma ◽

Zhenfei Hong ◽

Hailing Liu ◽

Xi Chen ◽

Lu Ding ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cancer Progression ◽

Cox Regression ◽

Roc Curves ◽

Endogenous Retroviruses ◽

Human Endogenous Retroviruses ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Kaplan Meier

Background. The association between human endogenous retroviruses-K (HERV-K) (HML-2) and human disease, including a variety of cancers, has been indicated. However, the function of HERV-K (HML-2) in the progression of hepatocellular carcinoma (HCC) still remains largely unclear.Methods. We detected the expression of HERV-K (HML-2) in 84 HCC tissues and adjacent nontumor tissues by quantitative real-time PCR (qRT-PCR) and analyzed its correlation with the clinical parameters.Result. The HEVR-K level was significantly increased in HCC compared with adjacent normal tissues (P<0.01) which was proved to be significantly associated with cirrhosis (P<0.05), tumor differentiation (P<0.05), and TNM stage (P<0.05). Moreover, the high expression of HERV-K (HML-2) had a poorer overall survival than patients with lower expression by a Kaplan-Meier survival analysis (P<0.01). The multivariate Cox regression analysis indicated that the level of HERV-K (HML-2) was an independent prognostic factor for the overall survival rate of HCC patients. Receiver operating characteristic (ROC) curves demonstrated the diagnostic accuracy of HERV-K (HML-2) expression in HCC (AUC = 0.729, 74.7% sensitivity, and 67.8% specificity).Conclusions. Our results suggested that upregulation of HERV-K (HML-2) in HCC patients was significantly related to cancer progression and poor outcome, indicating that HERV-K (HML-2) might be a novel candidate prognostic biomarker for HCC.

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The utilization of palliative radiation therapy to the liver for hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.474 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 474-474

Author(s):

Sara-Jane N. Onyeama ◽

Abdulrahman Y Hammad ◽

Fabian McCartney Johnston ◽

T. Clark Gamblin ◽

Jared Rex Robbins

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Radiation Therapy ◽

Cox Regression ◽

Intensity Modulated Radiation Therapy ◽

Treatment Schedule ◽

Palliative Radiation ◽

Palliative Intent ◽

Kaplan Meier ◽

Palliative Radiation Therapy

474 Background: Despite retrospective and prospective clinical trials conveying the efficacy of palliative radiation therapy (RT) to the liver, this modality is not commonly used. The purpose of this project is to evaluate trends, dose schemas, and techniques of palliative RT to the liver in current practice. We aim to identify factors associated with overall survival using patient data from the National Cancer Database (NCDB). Methods: Using the NCDB, we analyzed patients with hepatocellular carcinoma (HCC) diagnosed from 2004-2012 treated with palliative RT. Various patient factors were reviewed and survival analyses were performed. Doses were converted to biological effective dose (BED) to compare the different fractionation schemas. Univariate and multivariate analyses were performed with Kaplan Meier and Cox regression tests. Results: A total of 3,267 HCC patients were identified who were treated with palliative intent. Of these 877 (27%) received radiation therapy and only 138 (4% of total, 16% of RT) received radiation therapy to the liver. For those treated with palliative radiation to the liver, the median age was 61 years. Patients with stages I, II, III and IV disease comprised 15%, 15%, 45%, and 25% respectively. Various dose schema and techniques were used. 38% were treated with advanced radiation techniques (24% stereotactic body radiation therapy (SBRT), 14% Intensity-modulated radiation therapy (IMRT). A total of 79 (57%) patients received 10 or fewer fractions, but 32 (40%) of those were SBRT. The median survival was 4.7 months with 16% mortality at 1 month. On multivariate analysis, stage 3 (HR 2.625, p = 0,013) and stage 4 tumors (HR 2.701, p = 0.018), no chemotherapy (HR 1.743, p = 0.025), and lower radiation dose (HR 0.982, p = 0.003) was associated with worse overall survival. Conclusions: Palliative radiation to the liver is not frequently used in patients with HCC. As a result, there is minimal standardization of dose, modality, or treatment schedule. Better understanding of prognostic factors may help better determine the most appropriate plan for each patient to coordinate treatment length with projected survival.

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Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.4565 ◽

2007 ◽

Vol 25 (18) ◽

pp. 2586-2593 ◽

Cited By ~ 683

Author(s):

Qiang Gao ◽

Shuang-Jian Qiu ◽

Jia Fan ◽

Jian Zhou ◽

Xiao-Ying Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Cox Regression ◽

Independent Predictor ◽

Cytotoxic T Cells ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Tissue Microarrays ◽

Kaplan Meier ◽

Infiltrating Lymphocytes

Purpose To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. Patients and Methods CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. Results CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8+ cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031). Conclusion Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.

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High Expression of SRD5A3 in Human Hepatocellular Carcinoma (HCC) Predicts Poor Prognosis: A Study Based on TCGA Data

10.21203/rs.3.rs-1118583/v1 ◽

2021 ◽

Author(s):

Jing Xue ◽

Xianzhao Yang ◽

Feng Jiang

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Overall Survival ◽

Poor Prognosis ◽

Cox Regression ◽

High Expression ◽

Th2 Cells ◽

Kaplan Meier ◽

Potential Biomarker ◽

Pathologic Features

Abstract Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Steroid 5 alpha-reductase 3 (SRD5A3) was reported to be up-regulated in many types of cancer. However, its expression and role in HCC remains to be elucidated. We aim to evaluate the significance of SRD5A3 expression in HCC by using analysis of a public dataset from The Cancer Genome Atlas (TCGA).Methods: The relationship between clinical pathologic features and SRD5A3 were analyzed with the Kolmogorov‐Smirnov test and the logistic regression. Cox regression and the Kaplan-Meier method were used to assess the clinicopathologic characteristics associated with overall survival (OS) in TCGA patients. In addition, GSEA was used to predict potential hallmarks associated with different expression of SRD5A3 on transcriptional sequences from TCGA database.Results: SRD5A3 was highly expressed in HCC tumor tissue compared to normal tissue. A total of 184 upregulated DEGs (differentially expressed genes) and 58 downregulated DEGs were identified between high expression and low expression of SRD5A3. Among them, 22 hub genes mainly belonging to the keratin and MUC family demonstrated by connectivity degree in the PPI network were screened out. Kaplan-Meier method showed that HCC patients in the high SRD5A3 expression group had poorer overall survival (OS, HR=2.26(1.58-3.24), p<0.001). In addition, cell cycle mitotic, cell cycle checkpoints, mitotic nuclear division, Q-glycan processing, protein O-linked glycosylation were differentially enriched in the high SRD5A3 expression phenotype pathway. In addition, SRD5A3 expression level has significant correlations with infiltrating levels of Th17 (R = -0.238, p < 0.001), Cytotoxic cells (R = -0.234, p < 0.001) and Th2 cells (R = 0.258, p < 0.001) in HCC.Conclusions: High expression of SRD5A3 was significantly correlated with poor prognosis in HCC patients. It may be a potential biomarker in HCC.

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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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Nomograms Predicting Long-Term Overall Survival and Cancer-Specific Survival in Metastatic Hepatocellular Carcinoma Patients: A SEER Population-Based Study

10.21203/rs.3.rs-37178/v1 ◽

2020 ◽

Author(s):

Chi Cui ◽

Yaru Duan ◽

Rui Li ◽

Hua Ye ◽

Peng Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

Training Group ◽

Population Based ◽

Validation Group ◽

Cancer Specific Survival ◽

Term Survival ◽

Metastatic Hepatocellular Carcinoma

Abstract Background: This study aims to evaluate the clinicopathological characteristics of metastatic hepatocellular carcinoma (HCC) patients and develop nomograms to predict their long-term overall survival (OS) and cancer-specific survival (CSS). Methods: Information on metastatic HCC from 2010 to 2015 was retrieved from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. The metastatic HCC patients were divided into a long-term survival (LTS) group and a short-term survival (STS) group with 1 year selected as the cut-off value. Then, we compared the demographic and clinicopathological features between the two groups. Next, all patients were randomly divided into a training group and validation group at a 7:3 ratio. Univariate and multivariate Cox regression analyses were used to identify potential predictors for OS and CSS in the training group, and nomograms of OS and CSS were established. These predictive models were further validated in the validation group. Results: A total of 2163 patients were included in the current study according to the inclusion and exclusion criteria. Patients with characteristics including lower T stage and N stage; treatment with surgery, radiation or chemotherapy; no lung metastasis; and AFP negative status showed better survival. The concordance index (C-index) of the OS nomogram was 0.72 based on 9 variables. The C-index of the CSS nomogram was 0.71 based on 8 variables.Conclusions: These nomograms may help clinicians make better treatment recommendations for metastatic HCC patients.

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