scholarly journals Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection

2021 ◽  
Vol 11 ◽  
Author(s):  
Chihao Zhang ◽  
Jiayun Lin ◽  
Xiaochun Ni ◽  
Hongjie Li ◽  
Lei Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Radical Resection ◽  
Sensitivity Analyses ◽  
Patients With Cancer ◽  
Kaplan Meier ◽  
Restricted Mean Survival Time ◽  
Cox Analysis

BackgroundMultiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients’ prognosis.MethodsA total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People’s Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients’ survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM).ResultsPatients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40–2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39–2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716–0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25–2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20–2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses.ConclusionIn a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

scholarly journals The prognostic value of an autophagy-related lncRNA signature in hepatocellular carcinoma

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shiming Yang ◽  
Yaping Zhou ◽  
Xiangxin Zhang ◽  
Lu Wang ◽  
Jianfeng Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Score ◽  
Rna Splicing ◽  
Cox Regression ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Cox Regression Analysis ◽  
Risk Patients ◽  
Prognostic Prediction ◽  
Cox Analysis

Abstract Background lncRNA may be involved in the occurrence, metastasis, and chemical reaction of hepatocellular carcinoma (HCC) through various pathways associated with autophagy. Therefore, it is urgent to reveal more autophagy-related lncRNAs, explore these lncRNAs’ clinical significance, and find new targeted treatment strategies. Methods The corresponding data of HCC patients and autophagy genes were obtained from the TCGA database, and the human autophagy database respectively. Based on the co-expression and Cox regression analysis to construct prognostic prediction signature. Results Finally, a signature containing seven autophagy-related lncRNAs (PRRT3-AS1, RP11-479G22.8, RP11-73M18.8, LINC01138, CTD-2510F5.4, CTC-297N7.9, RP11-324I22.4) was constructed. Based on the risk score of signature, Overall survival (OS) curves show that the OS of high-risk patients is significantly lower than that of low-risk patients (P = 2.292e−10), and the prognostic prediction accuracy of risk score (AUC = 0.786) is significantly higher than that of ALBI (0.532), child_pugh (0.573), AFP (0.5751), and AJCC_stage (0.631). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are obviously accuracy by the combined analysis of the risk score, child_pugh, age, M_stage, and Grade (The AUC of 1- and 3-years are 0.87, and 0.855). Remarkably, the 7 autophagy-related lncRNAs may participate in Spliceosome, Cell cycle, RNA transport, DNA replication, and mRNA surveillance pathway and be related to the biological process of RNA splicing and mRNA splicing. Conclusion In conclusion, the 7 autophagy-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

scholarly journals Connection Between EIF3S3 Polymorphisms and Hepatocellular Carcinoma Prognosis

2020 ◽  
Author(s):  
Chao Yang ◽  
Peng Du ◽  
Wei Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Initiation Factor ◽  
Mrna Levels ◽  
Clinical Role ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Background: EIF3S3 that encodes a p40 subunit of eukaryotic initiation factor 3 (eIF3), has been reported overexpression in several human malignancies. The expression of EIF3S3 in hepatocellular carcinoma (HCC) and its clinical role in the disease progression is still unclear. Here we aimed to study the effect of EIF3S3 on HCC prognosis.Methods: Quantitative real-time polymerase chain-reaction (qRT-PCR) was performed to assess the mRNA levels of EIF3S3 in 120 HCC tissues samples and 60 adjacent noncancerous specimens. Kaplan-Meier and Cox regression analysis was used to study the prognostic value of EIF3S3.Results: The expression of EIF3S3 was significantly increased in HCC compared to the expression found in adjacent tissues (P<0.001). Furthermore, high EIF3S3 expression was positively correlated with vascular invasion, tumor size, cirrhosis, AFP levels and TNM stage (all P<0.05). Kaplan-Meier survival analysis showed that patients with high EIF3S3 expression had worse overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001) than those with low EIF3S3 expression. In addition, multivariable analysis revealed that EIF3S3 could be an independent prognostic factor of OS (P<0.001) and DFS (P<0.001) for patients with HCC.Conclusion: The results suggested that EIF3S3 might serve as a promising prognostic factor for OS and DFS of HCC patients.

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

2007 ◽  
Vol 25 (18) ◽  
pp. 2586-2593 ◽  
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.

scholarly journals TINCR expression is associated with unfavorable prognosis in patients with hepatocellular carcinoma

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Feng Tian ◽  
Jian Xu ◽  
Fangxi Xue ◽  
Encui Guan ◽  
Xiaoguang Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Kaplan Meier ◽  
Promising Target ◽  
Differentiation Status

Emerging evidence are accumulating that long noncoding RNAs (lncRNAs) have recently been identified to participate in various cellular processes. Terminal differentiation induced ncRNA (TINCR) is a newly identified lncRNA with its functional roles not fully elucidated in human malignancy. The current study aims to identify the clinical significance of TINCR in prognosis and malignant progression of hepatocellular carcinoma (HCC). TINCR expression in HCC specimens at various stages of tumorigenesis were measured by quantitative real-time RT PCR (qRT-PCR). The matched para-carcinoma tissues were used as controls. The associations of TINCR with clinicopathological characteristics, disease-free survival (DFS) and overall survival (OS) of patients were further evaluated. Results revealed that high TINCR expression was significantly correlated with tumor size (P=0.005), tumor differentiation status (P=0.017), TNM stage (P=0.010), and vascular invasion (P=0.004). Moreover, Kaplan–Meier analysis demonstrated that TINCR was correlated to both DFS and OS in HCC cohorts. Patients with high TINCR expression tended to have worse prognosis. Multivariate Cox regression analysis indicated that TINCR was an independent poor prognostic indicator for DFS (HR =1.32, 95% CI: 1.00–1.57, P=0.000) and OS (HR =1.57, 95% CI: 1.30–1.86, P=0.004) in HCC. TINCR was demonstrated as a direct target of miR-137 and miR-133a, and was suppressed by miR-137/miR-133a. These results provide the first evidence that the expression of TINCR in HCC may play an oncogenic role in HCC differentiation, invasion, and metastasis. miR-137/miR-133a-TINCR pathway may serve as a promising target for tumor recurrence and prognosis of patients with HCC.

scholarly journals Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer

Oncology ◽  
2020 ◽  
Vol 99 (1) ◽  
pp. 49-56
Author(s):  
Di Maria Jiang ◽  
Hao-Wen Sim ◽  
Osvaldo Espin-Garcia ◽  
Bryan A. Chan ◽  
Akina Natori ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Sensitivity Analyses ◽  
Trimodality Therapy ◽  
Gastroesophageal Junction Cancer ◽  
Kaplan Meier

<b><i>Background:</i></b> Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. <b><i>Methods:</i></b> A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. <b><i>Results:</i></b> Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (<i>n</i> = 67; 72%) or dCRT (<i>n</i> = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; <i>p</i> = 0.001; HR 3.1; 95% CI: 1.2–7.7) and DFS (0 vs. 41%; <i>p</i> = 0.004; HR 3.6; 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. <b><i>Conclusions:</i></b> TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

scholarly journals A Novel Post-Operative ALRI Model Accurately Predicts Clinical Outcomes of Resected Hepatocellular Carcinoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Minjun Liao ◽  
Jiarun Sun ◽  
Qifan Zhang ◽  
Cuirong Tang ◽  
Yuchen Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Analysis ◽  
Prediction Models ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Radical Resection ◽  
Risk Groups ◽  
Receiver Operating Curve ◽  
Term Survival ◽  
Prognostic Prediction

BackgroundHepatocellular carcinoma (HCC) is one of the leading malignant tumors worldwide. Prognosis and long-term survival of HCC remain unsatisfactory, even after radical resection, and many non-invasive predictors have been explored for post-operative patients. Most prognostic prediction models were based on preoperative clinical characteristics and pathological findings. This study aimed to investigate the prognostic value of a newly constructed nomogram, which incorporated post-operative aspartate aminotransferase to lymphocyte ratio index (ALRI).MethodsA total of 771 HCC patients underwent radical resection from three medical centers were enrolled and grouped into the training cohort (n = 416) and validation cohort (n = 355). Prognostic prediction potential of ALRI was assessed by receiver operating curve (ROC) analysis. The Cox regression model was used to identify independent prognostic factors. Nomograms for overall survival (OS) and disease-free survival (DFS) were constructed and further validated externally.ResultsThe ROC analysis ranked ALRI as the most effective prediction marker for resected HCC patients, with the cut-off value determined at 22.6. Higher ALRI level positively correlated with larger tumor size, higher tumor node metastasis (TNM) stage, and inversely with lower albumin level and shorter OS and DFS. Nomograms for OS and DFS were capable of discriminating HCC patients into different risk-groups.ConclusionsPost-operative ALRI was of prediction value for HCC prognosis. This novel nomogram may categorize HCC patients into different risk groups, and offer individualized surveillance reference for post-operative patients.

scholarly journals Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junbin Yan ◽  
Jielu Cao ◽  
Zhiyun Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Risk Score ◽  
Roc Curve ◽  
Prognostic Model ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter

Abstract Background Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients based on the Args. Methods We downloaded mRNA expression profiles and corresponding clinical data of Asian HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The Args were collected from Deathbase, a database related to cell death, combined with the research results of GeneCards、National Center for Biotechnology Information (NCBI) databases and a lot of literature. We used Wilcoxon-test and univariate Cox analysis to screen the differential expressed genes (DEGs) and the prognostic related genes (PRGs) of HCC. The intersection genes of DEGs and PGGs were seen as crucial Args of HCC. The prognostic model of Asian HCC patients was constructed by least absolute shrinkage and selection operator (lasso)- proportional hazards model (Cox) regression analysis. Kaplan-Meier curve, Principal Component Analysis (PCA) analysis, t-distributed Stochastic Neighbor Embedding (t-SNE) analysis, risk score curve, receiver operating characteristic (ROC) curve, and the HCC data of ICGC database and the data of Asian HCC patients of Kaplan-Meier plotter database were used to verify the model. Results A total of 20 of 56 Args were differentially expressed between HCC and adjacent normal tissues (p < 0.05). Univariate Cox regression analysis showed that 10 of 56 Args were associated with survival time and survival status of HCC patients (p < 0.05). There are seven overlapping genes of these 20 and 10 genes, including BAK1, BAX, BNIP3, CRADD, CSE1L, FAS, and SH3GLB1. Through Lasso-Cox analysis, an HCC prognostic model composed of BAK1, BNIP3, CSE1L, and FAS was constructed. Kaplan-Meier curve, PCA, t-SNE analysis, risk score curve, ROC curve, and secondary verification of ICGC database and Kaplan-Meier plotter database all support the reliability of the model. Conclusions Lasso-Cox regression analysis identified a 4-gene prognostic model, which integrates clinical and gene expression and has a good effect. The expression of Args is related to the prognosis of HCC patients, but the specific mechanism remains to be further verified.

scholarly journals Effect of prior cancer on survival of hepatocellular carcinoma: implications for clinical trial eligibility criteria

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuqi Sun ◽  
Lingling Li ◽  
Li Xu ◽  
Zhongguo Zhou ◽  
Jinbin Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Cox Regression ◽  
Tumor Stage ◽  
Eligibility Criteria ◽  
Cancer History ◽  
Cox Regression Analysis ◽  
Patients With Cancer ◽  
Kaplan Meier ◽  
Tumor Stages

Abstract Background Patients with cancer history are usually excluded from hepatocellular carcinoma (HCC) clinical trials. However, whether previous malignancy affects the oncological outcomes of HCC patients has not been fully assessed. This study aimed to evaluate whether prior cancer compromised the survival of HCC patients. Methods Patients with HCC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015, and then they were classified into groups with and without prior cancer. The Kaplan-Meier and multivariate Cox regression analysis were adopted to evaluate whether prior cancer impacted clinical outcomes after propensity score matching (PSM) adjusting baseline differences. Validation was performed in the cohort from our institution. Results We identified 2642 HCC patients with prior cancer. After PSM, the median overall survival (OS) time were 14.5 and 12.0 months respectively for groups with and without prior cancer. Prior cancer did not compromise prognosis in patients with HCC (p = 0.49). The same tendency was found in subgroups stratified by tumor stages and cancer interval period: OS was similar between groups with and without prior cancer (both p values> 0.1). In the multivariate Cox regression model, prior cancer did not adversely impact patients’ survival (HR: 1.024; 95% CI: 0.961–1.092). In the validation cohort from our institution, prior cancer had no significant association with worse outcomes (p = 0.48). Conclusion For HCC patients, prior cancer did not compromise their survival, regardless of tumor stage and cancer interval period. Exclusion criteria for HCC clinical trials could be reconsidered.

RESULTS OF TREATMENT OF LOCALLY RECURRING SOFT TISSUES SARCOMAS OF EXTREMITIES

2018 ◽  
Vol 64 (3) ◽  
pp. 408-413
Author(s):  
Grigoriy Zinovev ◽  
Georgiy Gafton ◽  
Sergey Novikov ◽  
Ivan Gafton ◽  
Yekaterina Busko ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Soft Tissues ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Tumor Location ◽  
Long Term Results ◽  
Clinical Feature ◽  
National Medical ◽  
Results Of Treatment ◽  
Kaplan Meier

Background: The most striking clinical feature of soft tissues sarcomas (STS) is their ability to recur. At present disputes about the clinical and morphological factors of STS recurrence such as the degree of malignancy, size, location, depth of tumor location, patient’s age and the presence of previous relapses in the anamnesis do not subside. It also requires clarification of the effect of the volume of tissues removed on the long-term results of treatment of STS as well as indications for the application of various regimes of remote radiation therapy. Materials and methods: Of 1802 registered cases of STS of extremities at the N.N. Petrov National Medical Research Center of Oncology from 2004 to 2016 there were selected data on 213 patients who suffered from at least one relapse of the disease. There was performed an assessment of overall, non-metastatic and disease-free survival using a single-factor (the Kaplan-Meier method) and multivariate analysis (the Cox regression model). Conclusion: The detection of various prognostic factors of locally recurrent STS allows determining the necessary treatment tactics (the vastness and traumatism of surgery and the advisability of radiation therapy).

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