The Efficacy of Radiotherapy in the Treatment of Hepatocellular Carcinoma with Distant Organ Metastasis

Background. Recently, radiotherapy has been used in the treatment of hepatocellular carcinoma (HCC). However, there is no study analyzing the efficacy of radiotherapy in cases of advanced HCC. The objective of this investigation was to determine the efficacy of radiotherapy in patients with HCC invading distant organs. Methods. The data of 2342 patients diagnosed between 2010 and 2015 with HCC invading distant organs were extracted from the SEER database. Propensity score matching (PSM) was used to reduce selection bias. Results. Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group (mOS = 5 months, 95% CI: 4.5–5.5; mCSS = 5 months, 95% CI: 4.4–5.6) were longer than those in the nonradiotherapy group (mOS = 3 months, 95% CI: 2.8–3.2; mCSS = 3 months, 95% CI: 2.8–3.2; both P < 0.001 ). After PSM, mOS in the radiotherapy group (5 months, 95% CI: 4.5–5.5) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6–3.4; P < 0.001 ), and the mCSS in the radiotherapy group (5 months, 95% CI: 4.4–5.6) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6–3.4; P < 0.001 ). Before PSM, the multivariate analysis showed that all-cause and cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group. The adjusted Cox regression analysis for subgroups showed that, in the nonradiotherapy group, patients with bone metastases and multiorgan metastases had a worse survival than those in the radiotherapy group. Conclusion. HCC patients with metastases to distant organs obtain survival benefit from radiotherapy, particularly patients with bone metastases and multiorgan metastases.

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Effects of marital status on overall and cancer-specific survival in laryngeal cancer patients: a population-based study

Scientific Reports ◽

10.1038/s41598-020-80698-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhao Ding ◽

Deshun Yu ◽

Hefeng Li ◽

Yueming Ding

Keyword(s):

Marital Status ◽

Cancer Patients ◽

Laryngeal Cancer ◽

Cox Regression ◽

Group Analysis ◽

Population Based ◽

Cancer Specific Survival ◽

Cox Regression Analysis ◽

Prognostic Effect ◽

The Difference

AbstractMarital status has long been recognized as an important prognostic factor for many cancers, however its’ prognostic effect for patients with laryngeal cancer has not been fully examined. We retrospectively analyzed 8834 laryngeal cancer patients in the Surveillance Epidemiology and End Results database from 2004 to 2010. Patients were divided into four groups: married, widowed, single, and divorced/separated. The difference in overall survival (OS) and cancer-specific survival (CSS) of the various marital subgroups were calculated using the Kaplan–Meier curve. Multivariate Cox regression analysis screened for independent prognostic factors. Propensity score matching (PSM) was also conducted to minimize selection bias. We included 8834 eligible patients (4817 married, 894 widowed, 1732 single and 1391 divorced/separated) with laryngeal cancer. The 5-year OS and CSS of married, widowed, single, and separated/divorced patients were examined. Univariate and multivariate analyses found marital status to be an independent predictor of survival. Subgroup survival analysis showed that the OS and CSS rates in widowed patients were always the lowest in the various American Joint Committee on Cancer stages, irrespective of sex. Widowed patients demonstrated worse OS and CSS in the 1:1 matched group analysis. Among patients with laryngeal cancer, widowed patients represented the highest-risk group, with the lowest OS and CSS.

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The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

British Journal of Cancer ◽

10.1038/s41416-021-01445-3 ◽

2021 ◽

Author(s):

Philip J. Johnson ◽

Sofi Dhanaraj ◽

Sarah Berhane ◽

Laura Bonnett ◽

Yuk Ting Ma

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Prognostic Factor ◽

Cox Regression ◽

Prognostic Models ◽

Controlled Study ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

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Trends of incidence and prognosis of primary adenocarcinoma of the bladder

Therapeutic Advances in Urology ◽

10.1177/17562872211018006 ◽

2021 ◽

Vol 13 ◽

pp. 175628722110180

Author(s):

Haowen Lu ◽

Weidong Zhu ◽

Weipu Mao ◽

Feng Zu ◽

Yali Wang ◽

...

Keyword(s):

Prediction Model ◽

Marital Status ◽

Cox Regression ◽

Tnm Staging ◽

Primary Site ◽

Primary Adenocarcinoma ◽

Cancer Specific Survival ◽

Training Cohort ◽

Cox Regression Analysis ◽

Ajcc Stage

Background: Primary adenocarcinoma of the bladder (ACB) is a rare malignant tumor of the bladder with limited understanding of its incidence and prognosis. Methods: Patients diagnosed with ACB between 2004 and 2015 were obtained from the SEER database. The incidence changes of ACB patients between 1975 and 2016 were detected by Joinpoint software. Nomograms were constructed based on the results of multivariate Cox regression analysis to predict overall survival (OS) and cancer-specific survival (CSS) in patients with ACB, and the constructed nomograms were validated. Results: The incidence of ACB was trending down from 1991 to 2016. A total of 1039 patients were included in the study and randomly assigned to the training cohort (727) and validation cohort (312). In the training cohort, multivariate Cox regression showed that age, marital status, primary site, histology type, grade, AJCC stage, T stage, SEER stage, surgery, radiotherapy, and chemotherapy were independent prognostic factors for OS, whereas these were age, marital status, primary site, histology type, grade, AJCC stage, T/N stage, SEER stage, surgery, and radiotherapy for CSS. Based on the above Cox regression results, we constructed prognostic nomograms for OS and CSS in ACB patients. The C-index of the nomogram OS was 0.773 and the C-index of CSS was 0.785, which was significantly better than the C-index of the TNM staging prediction model. The area under the curve (AUC) and net benefit of the prediction model were higher than those of the TNM staging system. In addition, the calibration curves were very close to the ideal curve, suggesting appreciable reliability of the nomograms. Conclusion: The incidence of ACB patients showed a decreasing trend in the past 25 years. We constructed a clinically useful prognostic nomogram for calculating OS and CSS of ACB patients, which can provide a personalized risk assessment for ACB patient survival.

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A long non-coding RNA-based signature predicts early recurrence in hepatocellular carcinoma

Cancer Biomarkers ◽

10.3233/cbm-210193 ◽

2021 ◽

pp. 1-10

Author(s):

Shuai He ◽

Jin-Feng Li ◽

Hao Tian ◽

Ye Sang ◽

Xiao-Jing Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Curative Resection ◽

Risk Model ◽

Cox Regression ◽

Early Recurrence ◽

Support Vector ◽

Term Survival ◽

Cox Regression Analysis ◽

Non Coding Rna ◽

Long Non Coding Rna

BACKGROUND: Early recurrence is the main obstacle for long-term survival of hepatocellular carcinoma (HCC) patients after curative resection. OBJECTIVE: We aimed to develop a long non-coding RNA (lncRNA) based signature to predict early recurrence. METHODS: Using bioinformatics analysis and quantitative reverse transcription PCR (RT-qPCR), we screened for lncRNA candidates that were abnormally expressed in HCC. The expression levels of candidate lncRNAs were analyzed in HCC tissues from 160 patients who underwent curative resection, and a risk model for the prediction of recurrence within 1 year (early recurrence) of HCCs was constructed with linear support vector machine (SVM). RESULTS: A lncRNA-based classifier (Clnc), which contained nine differentially expressed lncRNAs including AF339810, AK026286, BC020899, HEIH, HULC, MALAT1, PVT1, uc003fpg, and ZFAS1 was constructed. In the test set, this classifier reliably predicted early recurrence (AUC, 0.675; sensitivity, 72.0%; specificity, 63.1%) with an odds ratio of 4.390 (95% CI, 2.120–9.090). Clnc showed higher accuracy than traditional clinical features, including tumor size, portal vein tumor thrombus (PVTT) in predicting early recurrence (AUC, 0.675 vs 0.523 vs 0.541), and had much higher sensitivity than Barcelona Clinical Liver Cancer (BCLC; 72.0% vs 50.0%), albeit their AUCs were comparable (0.675 vs 0.678). Moreover, combining Clnc with BCLC significantly increased the AUC, compared with Clnc or BCLC alone in predicting early recurrence (all P< 0.05). Finally, logistic and Cox regression analysis suggested that Clnc was an independent prognostic factor and associated with the early recurrence and recurrence-free survival of HCC patients after resection, respectively (all P= 0.001). CONCLUSIONS: Our lncRNA-based classifier Clnc can predict early recurrence of patients undergoing surgical resection of HCC.

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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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Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8859558 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Rongjie Zhang ◽

Yan Chen ◽

Ge Zhou ◽

Baoguo Sun ◽

Yue Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Survival Analysis ◽

Regression Model ◽

Target Genes ◽

Cox Regression ◽

Risk Group ◽

Cox Regression Analysis ◽

Expression Levels ◽

Prognostic Analysis ◽

Significant Difference

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

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Identification of Immune-Related Prognostic mRNA and lncRNA in Patients with Hepatocellular Carcinoma

Journal of Oncology ◽

10.1155/2022/5313149 ◽

2022 ◽

Vol 2022 ◽

pp. 1-16

Author(s):

Dan Chen ◽

Xiaoting Li ◽

Hui Li ◽

Kai Wang ◽

Xianghua Tian

Keyword(s):

Hepatocellular Carcinoma ◽

Flow Cytometry ◽

T Cells ◽

Regression Analysis ◽

Survival Analysis ◽

Immune Cells ◽

Cox Regression ◽

Differentially Expressed ◽

Cox Regression Analysis ◽

Immune Related Genes

Background. As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods. In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results. Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC 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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Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.788640 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shaodi Wen ◽

Yuzhong Chen ◽

Chupeng Hu ◽

Xiaoyue Du ◽

Jingwei Xia ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systemic Inflammation ◽

Cox Regression ◽

Primary Liver Cancer ◽

Paraffin Section ◽

Neutrophil To Lymphocyte Ratio ◽

Survival Prediction ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Inflammation Parameters

BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC.Materials and MethodsWe retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients.ResultsWe first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice.ConclusionThe combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in 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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