Effect of combined consideration of distinct signatures of VEGF and soluble VEGFR2 on prognostic implication in gastric cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 56-56
Author(s):  
Chan-Young Ock ◽  
Ah-Rong Nam ◽  
Ju-Hee Bang ◽  
Tae-Yong Kim ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Growth Factor ◽  
Cox Regression ◽  
Linear Regression Analysis ◽  
Vegf Receptor ◽  
Prognostic Impact ◽  
Prognostic Implication ◽  
Cox Regression Analysis ◽  
Fibroblast Growth Factor Basic

56 Background: Anti-angiogenic strategy in gastric cancer (GC) has been highlighted again due to the recent success of ramucirumab and apatinib. Therefore, the comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC and their prognostic impact would be of importance, although they have been poorly understood. We aimed to find out the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. Methods: We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 patients who were diagnosed with GC in Seoul National University Hospital, and treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis by log rank test and Cox regression analysis were performed. Results: The VEGF signature was shown to be associated with seven CAFs (interluekin [IL]-7, IL-12p70, IL-2Ra, IL-10, stem cell factor, Fibroblast growth factor-basic, IL-3). The sVEGFR2 signature was associated with IL-4 and platelet-derived growth factor beta, but VEGF and sVEGFR2 showed no association with each other. Patients with high VEGF had a tendency to have worse overall survival (OS) than those with low VEGF (11.2 months versus 16.7 months; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). Interestingly, the poor prognostic impact of high-VEGF was far significant in patients with low-sVEGFR2 (10.9 months versus 16.8 months; P = 0.036). With this perspective, VEGF/sVEGFR2 ratio was significantly correlated with worse OS in univariate as well as multivariate analysis (HR 1.78 [95% CI 1.08-2.94], P= 0.024). Conclusions: Based on the comprehensive network analysis of CAF, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC. Regarding the angiogenic aspect, VEGF/sVEGFR2 ratio is significantly correlated with survival outcome in GC.

The prognostic impact of hypoxia-inducible factor-1α and VEGF, IGF-2, p21, p53 expression in gastric adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4571-4571
Author(s):  
Y. Kakeji ◽  
K. Mizokami ◽  
Y. Sumiyoshi ◽  
K. Yoshinaga ◽  
H. Saeki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Cox Regression ◽  
Hypoxia Inducible Factor ◽  
Depth Of Invasion ◽  
Human Gastric Cancer ◽  
Prognostic Impact ◽  
P53 Expression ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

4571 Background: Hypoxia caused by either radiation or chemotherapy induces various intracellular adaptive responses, which contribute to tumor progression. The clinicopathological characteristics of human gastric cancer and the clinical outcomes were analyzed to investigate the effects of the expression of hypoxia-inducible factor1α (HIF-1α) and some related proteins, such as, vascular endothelial growth factor (VEGF), insulin-like growth factor-2 (IGF-2), p21, and p53 on the prognosis of human gastric cancer. Methods: The expressions of HIF-1α, VEGF, IGF-2, p21, and p53 proteins were determined by immunohistochemistry in 216 specimens of primary gastric cancer. Results: Of all 216 patients, 85 (39.4%) showed a positive expression of HIF-1α. In addition, the HIF-1α expression positively correlated with the tumor size and depth of invasion, while it was also more frequent in tumors with lymphatic invasion and undifferentiated adenocarcinomas. Though the VEGF expression significantly correlated with the HIF-1α expression, the expressions of IGF-2, p21 and p53 did not show any correlation. HIF-1α-positive/p21-negative tumors had a lower apoptotic index, and the patients with such tumors also had a significantly poorer prognosis. Similarly, HIF-1α-positive/p53-positive tumors had a significantly poorer prognosis. A multivariate Cox regression analysis showed the depth of invasion, lymph node metastasis, and HIF-1α positivity to all be independent prognostic factors in patients with gastric cancer. Conclusions: Based on the above findings, HIF-1α is therefore considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1α protein overexpression with the loss of p21 expression or nonfunctional p53 thus tends to indicate a dismal prognosis. Controlling hypoxia, especially in the HIF-1α pathways, may therefore hold the key to a greater individualization of therapy and also lead to the development of new treatments for patients with gastric cancer. No significant financial relationships to disclose.

scholarly journals Expression of LOX Suggests Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p < 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

scholarly journals Application value of nomogram and prognostic factors of gastric cancer patients who underwent D2 radical lymphadenectomy

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Guang-Chuan Mu ◽  
Yuan Huang ◽  
Zhi-Ming Liu ◽  
Xiang-Hua Wu ◽  
Xin-Gan Qin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Cox Regression ◽  
Term Survival ◽  
Long Term Survival ◽  
Cox Regression Analysis ◽  
Gastric Cancer Patients

Abstract Background The aim of this study was to explore the prognostic factors and establish a nomogram to predict the long-term survival of gastric cancer patients. Methods The clinicopathological data of 421 gastric cancer patients, who were treated with radical D2 lymphadenectomy by the same surgical team between January 2009 and March 2017, were collected. The analysis of long-term survival was performed using Cox regression analysis. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the 5-year survival rate probability. Results In the present study, the total overall 3-year and 5-year survival rates were 58.7 and 45.8%, respectively. The results of the univariate Cox regression analysis revealed that tumor staging, tumor location, Borrmann type, the number of lymph nodes dissected, the number of lymph node metastases, positive lymph nodes ratio, lymphocyte count, serum albumin, CEA, CA153, CA199, BMI, tumor size, nerve invasion, and vascular invasion were prognostic factors for gastric cancer (all, P < 0.05). However, merely tumor staging, tumor location, positive lymph node ratio, CA199, BMI, tumor size, nerve invasion, and vascular invasion were independent risk factors, based on the results of the multivariate Cox regression analysis (all, P < 0.05). The nomogram based on eight independent prognostic factors revealed a well-degree of differentiation with a concordance index of 0.76 (95% CI: 0.72–0.79, P < 0.001), which was better than the AJCC-7 staging system (concordance index = 0.68). Conclusion The present study established a nomogram based on eight independent prognostic factors to predict long-term survival in gastric cancer patients. The nomogram would be beneficial for more accurately predicting the prognosis of gastric cancer, and provide important basis for making individualized treatment plans following surgery.

Prognostic Impact of Cytogenetics and Early Response and Efficacy of Sequential High-Dose AraC and Idarubicin (S-HAI) in Patients with Refractory and Relapsed Acute Myeloid Leukemia (AML): Results of a Prospective Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 871-871
Author(s):  
Wolfgang Kern ◽  
Hubert Serve ◽  
Peter Staib ◽  
Christa Kerschgens ◽  
Anett Matylis ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prospective Study ◽  
Cox Regression ◽  
High Dose ◽  
Prognostic Impact ◽  
Prognostic Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
A Prospective Study ◽  
Refractory Aml

Abstract Management of patients with refractory and relapsed AML needs optimization. We performed a prospective study in these patients aiming at 1) the definition of the anti-leukemic efficacy of the S-HAI regimen; and 2) the evaluation of the prognostic impact of cytogenetic aberrations at relapse in the context of other prognostic parameters. Treatment consisted of AraC 1 g/sqm q 12 h days 1, 2, 8, and 9 and idarubicin 10 mg/sqm days 3, 4, 10, and 11. AraC was given at 3 g/sqm in patients under age 60 with refractory AML or relapse after CR1 <6 months. Fludarabine was given according to randomization at 15 mg/sqm 4 h before each dose of AraC. Between May 1996 and February 2004 306 patients were randomized, 261 are fully evaluable. The patients′ characteristics were median age 55 years (range, 18-83); refractory AML/relapse with CR1<6 months/relapse with CR1 >6 months 13%/25%/62%; cytogenetics at relapse favorable/intermediate/unfavorable/not available 7%/44%/24%/25%; secondary AML 7%. Median duration of neutropenia <1000/μl was 37 days. Non-hematologic side effects III°/IV° included diarrhea (21%), mucositis (19%), nausea/vomiting (17%), hyperbilirubinemia (12%), and bleeding (8%). Encontered infections were pneumonia 51%, FUO 41%, bacteremia 28%, abdominal 23%, and catheter-related 16%. Response rates were CR 39%, partial remission 7%, persistent leukemia 36%, early death 18%. Median event-free survival (EFS) was 2.4 months, meidan relapse-free survival was 5.9 months, and median overall survival was 6.2 months. In 38% of patients a change of karyotype between diagnosis and relapse occurred. In general, cytogenetics (CG) at relapse had a higher prognostic impact as compared to CG at diagnosis and therefore was included in the following analyses of prognostic parameters. CR rate was significantly related to duration of CR1 (CR1 0 months 29%; CR1 <6 months 14%; CR1 >6<18 months 52%; CR1 >18 months 56%; p<0.0001) and CG at relapse (favorable CG 85%; intermediate CG 44%; unfavorable CG 21%; p<0.0001) but not to age < vs. >60 years (40% vs. 39%). EFS and OS were significantly related to duration of CR1 (p=0.0001 and p=0.0004) and CG at relapse (p=0.0002 and p=0.0009). Logistic regression analysis revealed CG at relapse (p=0.006) as well as duration of CR1 (p=0.004) being independently related to CR rate. Cox regression analysis revealed CG at relapse (p=0.001) and duration of CR1 (p=0.014) being independently related to EFS. CG at relapse was the only parameter independently related to OS (p=0.001). The inclusion of the therapy-dependent parameter, residual bone marrow blasts at day 18 (day 18 blasts), revealed day 18 blasts being independently related to CR rate, EFS, and OS. These data indicate that 1) the S-HAI regimen confers a significant anti-leukemic efficacy in patients with relapsed and refractory AML unless unfavorable CG are present; and 2) CG at relapse is the most important prognostic parameter in these patients and day 18 blasts may be used to early identify treatment failure and guide the decision about alternative treatment approaches.

Natural History, Risk Factors and Prognostic Impact of Graft-Versus-Host Disease Classified According to the National Institute of Health Criteria in Patients Receiving Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 899-899 ◽  
Author(s):  
Theis H Terwey ◽  
Arturo Vega-Ruiz ◽  
Philipp G. Hemmati ◽  
Peter Martus ◽  
Ekkehart Dietz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Risk Factor ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Organ Manifestations ◽  
Grade Iii

Abstract Abstract 899 Introduction: The classic definition of acute (aGVHD) and chronic graft-versus-host disease (cGVHD) was based on a cut-off day 100 after transplantation, but this did not reflect that aGVHD can occur later and that symptoms of aGVHD and cGVHD can occur simultaneously. In 2005 a NIH consensus classification was proposed which included 1) classic aGVHD, occurring before day 100, 2) persistent, recurrent or late aGVHD occurring thereafter, 3) classic cGVHD and 4) an overlap syndrome with simultaneous features of aGVHD and cGVHD. Only few studies have evaluated this classification and no studies have determined the differential impact of reduced intensity (RIC) and myeloablative conditioning (MAC). Method: We retrospectively analyzed 202 AML patients who were transplanted between 1999 and 2008. 102 patients received RIC (generally 6×30 mg/m2 FLU, 4×4 mg/kg BU, 4×10 mg/kg ATG) and immunosuppression with CSA/MMF and 100 patients received MAC (generally 6×2 Gy TBI and 2×60 mg/kg CY) and CSA/MTX. Donors were HLA-matched related (n=82), -matched unrelated (n=88) or -mismatched (n=32). Result: Leukocyte recovery was faster after RIC than after MAC (14 vs. 19 days, P<0.001) but time to reach full donor chimerism was similar (60 vs. 56 days, P=0.12). The cumulative incidence of classic aGVHD was lower after RIC than after MAC (40 vs. 67%, P<0.001) and it occurred later (31 vs. 23 days, P=0.041). No difference was seen in organ manifestations and in the overall aGVHD grade. The cumulative incidence of late aGVHD was low and did not differ between RIC and MAC (9 vs. 7%, P=NS). 13/16 patients with late aGVHD had persistent or recurrent classic aGVHD and 3/16 had de novo late aGVHD. Late aGVHD was less severe after RIC (grade III/IV 22 vs. 86%, P=0.041). The first signs of cGVHD were observed on days 86 after RIC and 97 after MAC with median onset on days 167 and 237, respectively (P=NS). The cumulative incidence of cGVHD tended to be lower after RIC (36 vs. 51%, P=0.088) and it tended to be less severe. Organ manifestations were similar except for cGVHD of the joints and fascia which affected 11% of MAC but no RIC patients (P=0.0021). More than half of cGVHD cases were subclassified as overlap cGVHD with no significant differences between RIC and MAC (51 vs. 65%, P=0.26). In multivariate Cox regression analysis of the whole cohort the only significant risk factor for aGVHD was MAC (HR 2.33, 95%CI 1.51–3.59, p<0.001). In RIC patients the administration of bone marrow lead to less aGVHD (HR 0.13, 95%CI 0.016–0.98, P=0.047). The only relevant risk factor for late aGVHD was prior aGVHD (HR 3.65, 95%CI 1.040–12.81, P=0.043). The most important risk factors for cGVHD were prior aGVHD (HR 2.77, 95%CI 1.64–5.67, P<0.001), female-to-male transplantation (HR 1.94, 95%CI 1.12–3.35, P=0.017) and advanced disease (HR 1.95, 95%CI 1.2–3.1, P=0.018). In multivariate Cox regression analysis with GVHD as time-dependant covariate aGVHD grade III/IV (HR 2.41, 95%CI: 1.51–3.87, P=0.001) and late aGVHD grade III/IV (HR 3.037, 95%CI 1.29–7.18, P=0.011) were associated with inferior overall survival (OS) while moderate cGVHD had a positive effect (HR 0.42, 95%CI 0.18–0.97, P=0.043). Classic and overlap cGVHD had no differential prognostic impact. Conclusion: This study in AML patients shows that previously established GVHD risk factors remain valid for the new NIH classification. It also confirms the major impact of conditioning intensity on GVHD incidence, the negative prognostic impact of severe aGVHD and the benefit of moderate cGVHD. The new category late aGVHD may only include few patients but will allow more adequate allocation to therapies or clinical trials. Whether the subgroups classic and overlap cGVHD are clinically relevant remains to be determined. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High Expression of PABPC1 Predicts Worse Survival of Gastric Cancer Patients

2020 ◽  
Author(s):  
Tailai An ◽  
Lingna Deng ◽  
Zheng Yang ◽  
Cuicui Chai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Mrna Translation ◽  
High Expression ◽  
Depth Of Invasion ◽  
Cox Regression Analysis

Abstract Background: Gastric cancer (GC) is one of the most common cancers with one of the highest mortality rates. Unfortunately, underlying molecular mechanisms contributing to GC have not been fully illuminated. PABPC1 is involved in a series of processes, such as mRNA translation, and mRNA deadenylation and decay. We performed this study to clarify the role of PABPC1 in GC. Methods: To evaluate PABPC1 expressions in GC and normal tissues, we performed bioinformatics analysis of data from TCGA. PABPC1 expressions were evaluated by immunohistochemical (IHC) staining of 170 GC specimens. Associations between PABPC1 expression and clinicopathological variables were analyzed. Independent predictive factors for survival of GC patients were determined by Cox regression analysis. Results: It was revealed by bioinformatics analysis that compared with normal gastric tissues, PABPC1 expressions in GC tissues were significantly higher (P=0.002, paired) (P=3.605e^-9, unpaired). It was revealed that PABPC1 expression was significantly associated with tumor size (P=0.008), Borrmann classification (P=0.003), vessel invasion (P=0.017), depth of invasion (P=0.032), lymph node metastasis (P=0.001), and TNM stage (P=0.019). It was demonstrated through Cox regression analysis that PABPC1 expression was a predictive factor for both overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001) of GC patients. Conclusions: Compared with that of normal gastric tissue, expression level of PABPC1 in GC tissue was significantly higher and PABPC1,s high expression was significantly associated with poorer survival, suggesting its potential as a therapeutic biomarker for GC.

scholarly journals Integrated analysis of 1804 samples of six centers to construct and validate a robust immune-related prognostic signature associated with stromal cell abundance in tumor microenvironment for gastric cancer

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Junyu Huo ◽  
Ge Guan ◽  
Jinzhen Cai ◽  
Liqun Wu
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Risk Score ◽  
Stromal Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Integrated Analysis ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Stromal cells in tumor microenvironment could promote immune escape through a variety of mechanisms, but there are lacking research in the field of gastric cancer (GC). Methods We identified differential expressed immune-related genes (DEIRGs) between the high- and low-stromal cell abundance GC samples in The Cancer Genome Atlas and GSE84437 datasets. A risk score was constructed basing on univariate cox regression analysis, LASSO regression analysis, and multivariate cox regression analysis in the training cohort (n=772). The median value of the risk score was used to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE26253, n=432; GSE62254, n=300; GSE15459, n=191; GSE26901, n=109) from the Gene Expression Omnibus (GEO) database. The immune cell infiltration was quantified by the CIBERSORT method. Results The risk score contained 6 genes (AKT3, APOD, FAM19A5, LTBP3, NOV, and NOX4) showed good performance in predicting 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate of GC patients. The risk death and recurrence of GC patients growing with the increasing risk score. The patients were clustered into three subtypes according to the infiltration of 22 kinds of immune cells quantified by the CIBERSORT method. The proportion of cluster A with the worst prognosis in the high-risk group was significantly higher than that in the low-risk group; the risk score of cluster C subtype with the best prognosis was significantly lower than that of the other two subtypes. Conclusion This study established and validated a robust prognostic model for gastric cancer by integrated analysis 1804 samples of six centers, and its mechanism was explored in combination with immune cell infiltration characterization.

SO085CIRCULATING PCSK9 LEVEL PREDICTS RISK OF CARDIOVASCULAR EVENTS AND DEATH IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hyeon Seok Hwang ◽  
Jin Sug Kim ◽  
Yang-Gyun Kim ◽  
So-Young Lee ◽  
Shin Young Ahn ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Total Cholesterol ◽  
Cox Regression ◽  
Linear Regression Analysis ◽  
High Sensitivity ◽  
Statin Treatment ◽  
Multivariate Linear Regression Analysis ◽  
Cox Regression Analysis ◽  
Composite Events ◽  
Multiple Variables

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. Method A total of 353 HD patients were prospectively enrolled from June 2016 to May 2018 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. Patients were classified into three groups based on PCSK9 tertile. The primary endpoint was defined as composite of CV event and death from any cause. Results Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. However, PCSK9 was not related to plasma inflammatory (high-sensitivity C-reactive peptide, monocyte chemoattractant protein-1, interleukin-6) or calcification-related markers (osteoprotegerin and receptor activator of nuclear factor kappa-Β ligand). Multivariate linear regression analysis revealed that baseline statin treatment and serum glucose, albumin, and total cholesterol were independent determinants of circulating PCSK9 levels. In Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.99-fold risk for composite events (95% CI, 1.08–3.66), and it was associated with a 2.26-fold risk for CV events (95% CI, 1.11–4.62) after adjustment for multiple variables. PCSK9 tertile 3 provides additional prognostic power to predict composite events in subgroups with higher levels of high-sensitivity C-reactive peptide and LDL. Conclusion In conclusion, higher circulating PCSK9 level independently predicted CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition on reduction of CV events.

Prognostic impact of LDH and HCG levels in marker-positive seminomas.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 392-392 ◽  
Author(s):  
Christoph Alexander Seidel ◽  
Gedske Daugaard ◽  
Tim Nestler ◽  
Alexey Tryakin ◽  
Christian Daniel Fankhauser ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Serum Levels ◽  
Rank Test ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Oncological Outcomes ◽  
Log Rank Test

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy <1.5 UNL (n=142) had a 5-year CSS (RFS) rate of 97% (88%), compared to 86% (81%) for ≥1.5 to 3 UNL (n=40), 83% (77%) for >3 to 5 UNL (n=44) and 83% (72%) for >5 UNL (n=44) (CSS p <0.001; RFS p=0.142). Concerning LDH levels post-orchiectomy this stratification was not significant but patients with LDH levels ≥3 UNL (n=77) displayed an impaired prognosis associated with a 5-year CSS (RFS) rate of 85% (79%) compared to 94% (82%) for levels <3 UNL (n=186) (CSS p=0.025; RFS p=0.447). Patients with HCG levels ≥2000 IU/l (n=17) pre- but not post-orchiectomy had a 5-year CSS (RFS) rate of 73% (60%) compared to 94% (79%) for patients with HCG levels <2000 IU/l (n=855) (CSS p=0.09; RFS p=0.04). In cox-regression analysis LDH ≥1.5 UNL (p=0.037; HR 3.32, CI95%1.08-10.26) and HCG levels ≥2000 IU/l (p=0.044; HR 3.69, 95%CI1.04-13.13) pre-orchiectomy were confirmed as prognostic factors for CSS. Conclusions: LDH levels inversely correlate with survival outcomes, suggesting ≥1.5 UNL pre- and ≥3 UNL post-orchiectomy as potential cut-off values for further risk assessment. Patients with extensive HCG elevations may represent an unfavorable subgroup concerning RFS and CSS, but only few patients were affected.

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