scholarly journals Derivation and validation of a lipid-covered prognostic model for mature T-cell lymphomas

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tiange Lu ◽  
Lei Shi ◽  
Guanggang Shi ◽  
Yiqing Cai ◽  
Shunfeng Hu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
T Cell ◽  
Scoring System ◽  
Serum Lipid ◽  
Prognostic Model ◽  
Validation Cohort ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
T Cell Lymphomas

Abstract Background Mature T-cell lymphomas (MTCLs), a group of diseases with high aggressiveness and vulnerable prognosis, lack for the accurate prognostic stratification systems at present. Novel prognostic markers and models are urgently demanded. Aberrant lipid metabolism is closely related to the tumor progression but its prognostic significance in MTCLs remains unexplored. This study aims to investigate the relationship between dysregulated lipid metabolism and survival prognosis of MTCLs and establish a novel and well-performed prognostic scoring system for MTCL patients. Methods A total of 173 treatment-naive patients were enrolled in this study. Univariate and multivariate Cox regression analysis were performed to assess the prognostic significance of serum lipid profiles and screen out independent prognostic factors, which constituted a novel prognostic model for MTCLs. The performance of the novel model was assessed in the training and validation cohort, respectively, by examining its calibration, discrimination and clinical utility. Results Among the 173 included patients, 115 patients (01/2006–12/2016) constituted the training cohort and 58 patients (01/2017–06/2020) formed the validation cohort. Univariate analysis revealed declined total cholesterol (TC, P = 0.000), high-density lipoprotein cholesterol (HDL-C, P = 0.000) and increased triglycerides (TG, P = 0.000) correlated to inferior survival outcomes. Multivariate analysis revealed extranodal involved sites ≥ 2 (hazard ratio [HR]: 2.439; P = 0.036), β2-MG ≥ 3 mg/L (HR: 4.165; P = 0.003) and TC < 3.58 mmol/L (HR: 3.338; P = 0.000) were independent predictors. Subsequently, a novel prognostic model, EnBC score, was constructed with these three factors. Harrell’s C-index of the model in the training and validation cohort was 0.840 (95% CI 0.810–0.870) and 0.882 (95% CI 0.822–0.942), respectively, with well-fitted calibration curves. The model divided patients into four risk groups with distinct OS [median OS: not available (NA) vs. NA vs. 14.0 vs. 4.0 months, P < 0.0001] and PFS (median PFS: 84.0 vs. 19.0 vs. 8.0 vs. 1.5 months, P < 0.0001). Time-dependent receiver operating characteristic curve and decision curve analysis  further revealed that EnBC score provided higher diagnostic capacity and clinical benefit, compared with International Prognostic Index (IPI). Conclusion Firstly, abnormal serum lipid metabolism was demonstrated significantly related to the survival of MTCL patients. Furthermore, a lipid-covered prognostic scoring system was established and performed well in stratifying patients with MTCLs.

Clinical Characteristics and Prognostic Factors of Mature T-Cell Lymphomas. A Single Center Experience on 39 Cases.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4652-4652
Author(s):  
Vassiliki I. Pappa ◽  
George Mantzios ◽  
Christina Economopoulou ◽  
Theofanis Economopoulos ◽  
Efstathios Papageorgiou ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Median Survival ◽  
Scoring System ◽  
Clinical Characteristics ◽  
Prognostic Significance ◽  
Neoplastic Cell ◽  
Factors Associated ◽  
T Cell Lymphomas ◽  
Histological Characteristics

Abstract Introduction: Mature T cell lymphomas are a rare and heterogeneous group of malignancies characterized by a poor prognosis. They usually present with advanced-stage disease and generally have a significantly worse outcome compared with aggressive B-cell lymphomas. The aim of the present study was the retrospective analysis of clinical and laboratory characteristics of patients with mature T cell lymphomas with the view to identify factors of prognostic significance. Patients and Methods: 39 patients with mature T cell lymphoma, classified according to WHO classification, diagnosed in our institution within a 17 year period were analyzed. Cases with anaplastic and cutaneous lymphomas were excluded. There were 25 males and 14 females with a median age of 61 (26–80). 3 patients had stage I,. 7 stage II, 10 stage III and 19 stage IV disease. B symptoms were present in 28/39 cases and bulky disease in 6/39 cases. All cases were risk stratified according to the International Prognostic Index (IPI). 9 patients had IPI 0/1, 9 had IPI 2, 10 had IPI 3 and 8 IPI 4/5. In 3 cases the IPI could not be defined. 21 patients were treated with CHOP like therapy, 11 with COP and 7 with other treatment. The size and the immunophenotype of the neoplastic cell population in the diagnostic biopsy (Τ4, Τ8 or mixed), the patients’ clinical characteristics and their laboratory findings were analyzed to identify factors of prognostic significance. Results. 17/39 patients (47.6%) achieved CR, 7/39 PR, while 6 had stable and 7 progressive disease. 2 patients died during induction treatment. 21/39 patients developed recurrent disease and the median disease free survival (DFS) was 78 months. Factors associated with significantly worse DFS were age above 60 (p=0.0005) and the presence of hepatomegaly at diagnosis (3 vs 78 months, p=0.0219), while the presence of extranodal disease was of borderline significance (p=0.0629). The patients’ median survival was 24 months. Factors associated with significantly shorter survival were female gender (14 vs 61 months, p=0.0396), the presence of supradiaphragmatic disease (p=0.0337) and eosinophilia at diagnosis (p=0.0467). Τhe IPI scoring system could distinguish between groups with a significant difference both in DFS and overall survival. DFS for IPI 4/5 was significantly shorter vs IPI 0-3 (p=0.0009). Patients with IPI 0/1 had a median survival 271 months, with IPI 2/3 24 months and with IPI 4/5 8 months (p=0.002). Histological characteristics like cell size or immunophenotype of the neoplastic cell were not important for prognosis. Conclusions. Mature T cell lymphomas constitute an heterogenous group of aggressive lymphomas that can be prognostically evaluated using clinical parameters. The IPI scoring system can identify subgroups with significant differences both in terms of DFS and overall survival. The analysis of larger number of cases or of histological characteristics may be helpful in the identification of other clinical or laboratory parameters that will increase the discriminative capacity of the IPI scoring system in this group of aggressive lymphomas.

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 Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma

2020 ◽  
Vol 8 (2) ◽  
pp. e001467
Author(s):  
Abhishek Tripathi ◽  
Edwin Lin ◽  
Wanling Xie ◽  
Abdallah Flaifel ◽  
John A Steinharter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
T Cell ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Tcga Dataset ◽  
Cd73 Expression

BackgroundCD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR; ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.MethodsPatients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative (CS=0), CD73low or CD73high (< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and high NT5E, ENTPD1 and ADORA2A gene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared between NT5E, ENTPD1 and ADORA2A expression groups.ResultsAmong the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73high tumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negative group (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, high NT5E expression was associated with significantly worse 5-year OS (p=0.008). NT5E and ENTPD1 expression correlated with higher regulatory T cell (Treg) signature, while ADORA2A expression was associated with increased Treg and angiogenesis signatures.ConclusionsHigh CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.

scholarly journals Prognostic Significance of Pretreatment Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Patients with Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Siqian Wang ◽  
Yongyong Ma ◽  
Lan Sun ◽  
Yifen Shi ◽  
Songfu Jiang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Large B Cell Lymphoma ◽  
Large B Cell

It is generally believed that there is correlation between cancer prognosis and pretreatment PLR and NLR. However, there are limited data about their role in diffuse large B cell lymphoma (DLBCL). This study aims to determine the prognostic value of pretreatment PLR and NLR for patients who have DLBCL. The associations between clinical characteristics and NLR and PLR were evaluated among 182 DLBCL patients from January 2005 to June 2016. The optimal cutoff values for high PLR (⩾150) and NLR (⩾2.32) in prognosis prediction were determined. The effect of NLR and PLR on survival was evaluated through multivariate Cox regression analysis, univariate analysis, and log-rank test. According to the evaluation results, patients with high NLR and PLR had significantly shorter OS (P=0.026 and P=0.035) and PFS (P=0.024 and P=0.022) compared with those who have low PLR and NLR. On multivariate analyses, IPI>2, elevated LDH, and PLR⩾2.32 were prognostic factors for OS and PFS in DLBCL patients. Therefore, we demonstrated that high PLR and NLR predicted adverse prognostic factors in DLBCL patients.

NK/T Cell Versus Peripheral T Cell Lymphoma: Significant Differences in Clinical Characteristics and Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4600-4600
Author(s):  
Soon-Thye Lim ◽  
Fei Gao ◽  
Lay-Cheng Lim ◽  
Richard Quek ◽  
Daryl Lim ◽  
...  
Keyword(s):  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Advanced Stage ◽  
Peripheral T Cell Lymphoma ◽  
Nk T Cell

Abstract Background: To compare the clinico-pathologic characteristics and prognosis of Natural Killer/T cell lymphoma (NK/TL) with peripheral T cell lymphoma (PTCL). Methods: A total of 556 resident patients (pts) with lymphoma were treated in the departments of medical oncology and hematology in an Asian institution from 2000 to 2005. Of these pts, 71 (12.8%) had NK/TL or PTCL and were included in this analysis. Pathology was centrally reviewed and classified according to the WHO classification. Results: NK/TL and PTCL comprised of 4.7% (26/556) and 7.9% (45/556) of all cases. Of the PTCL cases, histology was PTCL-NOS in 21, anaplastic large cell in 12 (5 were ALK-1 positive) and angioimmunoblastic T cell in 8 pts. Subcutaneous panniculitis T cell and γ/δ T cell lymphoma accounted for one case each. There were no significant differences between the two groups of pts in terms of sex, performance status, extranodal involvement and LDH level at presentation. However, more patients with NK/TL presented with stage I/II disease (65% vs. 31%, p=0.003). Among pts with NK/TL, 17 (65%) received CHOP-based chemotherapy, 4 received radiation alone and 5 received palliative chemotherapy. In the PTCL group, 39 (87%) received CHOP-based chemotherapy, 2 received radiation alone and 3 received palliative treatment only. Compared to PTCL, NK/TL was associated with a significantly inferior rate of complete remission (27% vs. 58%, p=0.01) and inferior overall survival (5 vs. 28.4 mos, p=0.001). Although age &gt; 60, ECOG ≥ 2, elevated LDH, advanced stage, IPI ≥ 2 and NK/T cell histology were each associated with decreased survival on univariate analysis, only NK/T cell histology and advanced stage were independently associated with decreased survival (see table 1). Conclusions: Contrary to expectation, the incidence of PTCL based on WHO classification in this Asian series is not higher than that reported in Western series. Compared to PTCL, the NK/T subtype is associated with a paricularly inferior prognosis and overrides the prognostic significance of IPI. These data suggest that NK/TL should be considered as a seperate entity and should not be considered together with other subtypes of T cell lymphoma in clinical trials. Table 1. NK/TL vs. PTCL: Univariate and Multivariate Analyses Univariate Analysis Multivariate Analysis Median (yr) P Hazard Ratio 95% CI P Male vs. Female 1.03 vs. Not reached 0.06 0.62 0.28 to 1.40 0.25 Age&lt;60 vs. ≥ 60 2.37 vs. 0.51 0.01 1.41 0.70 to 2.83 0.33 ECOG 0/1 vs. ≥ 2 1.99 vs. 0.36 0.002 1.52 0.63 to 3.65 0.354 LDH normal vs. High Not reached vs. 0.75 0.03 1.29 0.53 to 3.13 0.57 Stage I/II vs. III/IV 1.99 vs. 1.41 0.16 2.91 1.17 to 7.2 0.02 IPI 0/1 vs. ≥ 2 Not Reached vs. 0.42 0.002 2.22 0.82 to 5.99 0.12 PTCL vs. NK/TL 2.37 vs. 0.42 0.001 5.8 2.36 to 14.24 &lt;0.001

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.

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