Coexpression of PDGFR-Alpha, PDGFR-Beta and VEGF as a Prognostic Factor in Patients with Hepatocellular Carcinoma

2011 ◽  
Vol 26 (2) ◽  
pp. 108-116 ◽  
Author(s):  
Li Chen ◽  
Yan Shi ◽  
Cheng-ying Jiang ◽  
Li-xin Wei ◽  
Ya-li Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Cox Regression Analysis

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.

scholarly journals Prognostic significance of p16, p53, Bcl-2, and Bax in oral and oropharyngeal squamous cell carcinoma

2014 ◽  
Vol 8 (2) ◽  
pp. 255-261
Author(s):  
Paramee Thongsuksai ◽  
Kowit Pruegsanusak ◽  
Pleumjit Boonyaphiphat
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
P53 Expression

Abstract Background: The proteins p16, p53, Bcl-2, and Bax are important cell cycle and apoptotic regulators involved in carcinogenesis and found to have prognostic significance in various cancers. However, the data for squamous cell carcinoma of oral cavity (OSCC) and of oropharynx (OPSCC) are conflicting. Objective: We sought to determine if expression of p16, p53, Bcl-2, and Bax expression are associated with 5-year overall survival (OS) of patients with OSCC and OPSCC. Methods: One-hundred thirty-seven cases of OSCC and 140 cases of OPSCC diagnosed from January 2002 to December 2004 at Songklanagrind Hospital, Songkhla, Thailand, were analyzed using a Cox proportional hazards model for 5-year OS in relation to immunohistochemical detection of Bcl-2, Bax, p53, and p16 proteins. Results: The frequencies of p16, p53, Bcl-2, and Bax expression in OSCC were 13%, 45%, 4%, and 66%, and in OPSCC were 18%, 53%, 22%, and 75%, respectively. In univariate analysis, clinical variables including T stage, N stage and treatment were significantly associated with survival. In multivariate Cox regression, Bax overexpression was significantly associated with poor survival both in OSCC (HR 1.77, 95% CI 1.04-3.01) and in OPSCC (HR 2.21, 95% CI 1.00-4.85). We found no significant association of p16, Bcl-2, and p53 expression with survival. Conclusion: The expression pattern of p16, p53, Bcl-2, and Bax are similar in OSCC and OPSCC. Only Bax expression has prognostic significance for both tumor sites.

scholarly journals FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

2018 ◽  
Vol 51 (6) ◽  
pp. 2716-2731 ◽  
Author(s):  
Dan Li ◽  
Suyun Fan ◽  
Fei Yu ◽  
Xuchao Zhu ◽  
Yingchun Song ◽  
...  
Keyword(s):  
Proportional Hazards Model ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Cox Proportional Hazards Model ◽  
Migration And Invasion ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Nsclc Patients

Background/Aims: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Results: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Conclusion: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients.

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

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

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

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

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.

scholarly journals Construction and Validation of a Metabolic Reprogramming Related Prognostic Model for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Xiaohong - Liu ◽  
Qian - Xu ◽  
Zi-Jing - Li ◽  
Bin - Xiong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Risk Score ◽  
Prognostic Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Metabolic Reprogramming ◽  
Cox Regression Analysis ◽  
Metabolic Genes

Abstract BackgroundMetabolic reprogramming is an important hallmark in the development of malignancies. Numerous metabolic genes have been demonstrated to participate in the progression of hepatocellular carcinoma (HCC). However, the prognostic significance of the metabolic genes in HCC remains elusive. MethodsWe downloaded the gene expression profiles and clinical information from the GEO, TCGA and ICGC databases. The differently expressed metabolic genes were identified by using Limma R package. Univariate Cox regression analysis and LASSO (Least absolute shrinkage and selection operator) Cox regression analysis were utilized to uncover the prognostic significance of metabolic genes. A metabolism-related prognostic model was constructed in TCGA cohort and validated in ICGC cohort. Furthermore, we constructed a nomogram to improve the accuracy of the prognostic model by using the multivariate Cox regression analysis.ResultsThe high-risk score predicted poor prognosis for HCC patients in the TCGA cohort, as confirmed in the ICGC cohort (P < 0.001). And in the multivariate Cox regression analysis, we observed that risk score could act as an independent prognostic factor for the TCGA cohort (HR (hazard ratio) 3.635, 95% CI (confidence interval)2.382-5.549) and the ICGC cohort (HR1.905, 95%CI 1.328-2.731). In addition, we constructed a nomogram for clinical use, which suggested a better prognostic model than risk score.ConclusionsOur study identified several metabolic genes with important prognostic value for HCC. These metabolic genes can influence the progression of HCC by regulating tumor biology and can also provide metabolic targets for the precise treatment of HCC.

scholarly journals Construction and Validation of a Prognostic Risk Model Based on Autophagy-Related Genes in Hepatocellular Carcinoma Cells

2021 ◽  
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Differential Expression ◽  
Prognostic Model ◽  
Risk Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Differential Expression Analysis ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

scholarly journals Trajectories of Mediterranean Diet Adherence and Risk of Hypertension in China: Results from the CHNS Study, 1997–2011

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 2014 ◽  
Author(s):  
Min Gao ◽  
Fengbin Wang ◽  
Ying Shen ◽  
Xiaorou Zhu ◽  
Xing Zhang ◽  
...  
Keyword(s):  
Mediterranean Diet ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Nutrition Survey ◽  
Cox Regression Analysis ◽  
Incident Hypertension ◽  
Diet Adherence ◽  
Mediterranean Diet Adherence

Evidence indicates that longitudinal changes in dietary patterns may predict variations in blood pressure (BP) and risk of incident hypertension. We aimed to identify distinct trajectories in the levels of Mediterranean diet adherence (MDA) in China and explore their association with BP levels and hypertension risk using the China Health and Nutrition Survey 1997–2011 data. Three levels of MDA were constructed. The trajectories in these levels were constructed using group-based trajectory modeling. A Cox proportional hazards model was used to measure the association between MDA trajectory groups and the risk of incident hypertension after adjusting for covariates. Finally, 6586 individuals were included. Six distinct MDA trajectory groups were identified: persistently low and gradual decline; rapidly increasing and stabilized; persistently moderate; slightly increasing, steady, and acutely descending; slightly decreasing and acutely elevated; and persistently high. The systolic BP and diastolic BP were significantly lower in trajectory groups with rapidly increasing and stabilized MDA; slightly increasing, steady, and acutely descending MDA; and persistently high MDA. Cox regression analysis showed that the risks of developing hypertension were relatively lower in the group with slightly increasing, steady, and acutely descending MDA (hazard ratio (HR) = 0.17, 95% confidence interval (CI): 0.09–0.32) and the group with rapidly increasing and stabilized MDA (HR = 0.32, 95% CI: 0.23–0.42), but the risk was the highest in the trajectory with persistently moderate MDA (HR = 0.96, 95% CI: 0.84–1.08). In conclusion, MDA in China was categorized into six distinct trajectory groups. BP was relatively lower in trajectory groups with initially high or increasing MDA levels. Greater MDA was significantly associated with a lower risk of developing hypertension.

Prognostic Factors Associated with Outcomes in Small Bowel Neuroendocrine Tumors

2017 ◽  
Vol 83 (10) ◽  
pp. 1174-1178 ◽  
Author(s):  
Nicholas Manguso ◽  
Jeffrey Johnson ◽  
Attiya Harit ◽  
Nicholas Nissen ◽  
James Mirocha ◽  
...  
Keyword(s):  
Small Bowel ◽  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Nodal Metastasis ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Open Operation ◽  
Recurrence Group

Small bowel neuroendocrine tumors (SBNET) account for most gastrointestinal neuroendocrine tumors. Patients often present with late-stage disease; however, there is little information regarding factors that contribute to recurrence. Database review identified 301 patients diagnosed with SBNET between 1990 and 2013. Univariate analysis included patients who underwent complete resection. Survival was estimated by the Kaplan–Meier method. A total of 147 patients met study criteria. Average age was 60 years (range 21–91); 49 per cent were male. Thirty-seven (25.3%) patients had laparoscopic resection, and 29 (19.9%) patients had only small bowel disease, whereas 108 (72.6%) had nodal metastasis. Five-year overall and disease-free survival were 97.5 and 73.5 per cent. Forty-seven (32%) patients had recurrence. The recurrence group was more likely to have an open operation (59.6 vs 32%, P < 0.01), mesenteric invasion, or lymphatic metastasis (87.2 vs 67%, P < 0.01) compared with the no-recurrence group. Cox regression analysis showed that variables associated with recurrence included nodal disease (HR 9.06, P = 0.03), lymphovascular invasion (LVI) (3.95, P < 0.01), perineural invasion (PNI) (3.48, P < 0.01), and mesenteric involvement (3.77, P = 0.03). Patients with SBNET presenting with nodal metastasis, mesenteric involvement, LVI, or PNI have a higher risk of recurrence. Closer surveillance should be considered after operative resection.

The influence of obesity on tumor recurrence in vulvar cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17130-e17130 ◽  
Author(s):  
Rüdiger Klapdor ◽  
Peter Hillemanns ◽  
Linn Lena Woelber ◽  
Julia Kathrin Jueckstock ◽  
Felix Hilpert ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Vulvar Cancer ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Tumor Diameter ◽  
Cox Regression Analysis

e17130 Background: Obesity is associated with worse patients’ survival in several cancer entities. Vulvar cancer as well as obesity show increasing incidence over the last years. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on prevention, treatment, and follow-up. Methods: This is an analysis of the large AGO-CaRE-1 study. Patients suffering from squamous cell vulvar cancer (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, were categorized in a database, in order to analyze treatment patterns and prognostic factors in a retrospective setting. Results: In total, 849 patients with documented height and weight were divided into two groups depending on their body mass index (BMI, < 30 vs. ≥30 kg/m²). There was no difference in the baseline variables (age, tumor diameter, depth of infiltration, tumor stage, nodal invasion, tumor grade) between both groups (p > 0.05). However, we identified differences regarding ECOG status and preexistent comorbidities (cardiovascular, dementia) towards healthier patients with BMI < 30 kg/m². Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ (p > 0.05). Patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1 % vs. 51.8%, p = 0.042). During follow-up, there was a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p < 0.01) due to an increased rate of local recurrences (33.3% vs. 18.5%, p < 0.01). The rate of groin and distant recurrences was similar between both groups (p > 0.05). Noteworthy, we observed a significantly shorter disease free survival (DSF) of the obese patients in univariate analysis (HR 1.362, 95%CI 1.093-1.696, p = 0.006). Even in multivariate Cox-regression analysis including age, ECOG, tumor stage, type of surgery, nodal invasion, tumor grade, and comorbidities patients with BMI ≥30 kg/m² had a significantly shorter DFS (HR 1.811, 95%CI 1.005-3.262, p = 0.048). Conclusions: In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence.

The Indications for Hepatectomy for Multinodular Hepatocellular Carcinoma: Experience from a Single Institution

2015 ◽  
Vol 32 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Yuan-da Zhou ◽  
Hui-kai Li ◽  
Yun-long Cui ◽  
Ti Zhang ◽  
Qiang Li
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Rank Test ◽  
Morbidity Rate ◽  
Single Institution ◽  
Multiple Tumor ◽  
Prognostic Risk Factors

Aims: This study was conducted in order to investigate the indications for hepatecomy for multinodular hepatocellular carcinoma (MNHCC) in single institution. Methods: We retrospectively analyzed the medical records from 55 MNHCC patients, mainly with Child-Pugh A liver function, who underwent hepatectomy from January 2006 to December 2008. Both short- and long-term outcomes were analyzed. In addition, the prognostic significance of clinicopathological factors on overall survival (OS) was investigated by univariate analysis using the log-rank test. A Cox proportional hazards model was used in a subsequent multivariate analysis. Results: The perioperative morbidity rate (grade II or higher) was 18.2% (n = 10), and the in-hospital mortality rate was 3.6%. The median OS was 23.9 months (range, 2.5-84 months), whereas the median disease-free survival was 8.75 months (range, 1-65 months). Independent prognostic risk factors of 5-year OS included the number of tumors >2 (p = 0.032) and gross morphology indicating multiple tumor nodules scattered throughout the liver (p = 0.009). Conclusions: The postoperative morbidity and mortality rates were acceptable. The number of tumors >2 and gross morphology indicating multiple tumor nodules scattered throughout the liver were independent prognostic risk factors for patients with MNHCC after hepatectomy. Patients with both of these features had a very poor prognosis and were not considered suitable for surgery.

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