scholarly journals Expression ofFOXP3,CD14, andARG1in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Stigliani ◽  
Michela Croce ◽  
Fabio Morandi ◽  
Paola Scaruffi ◽  
Valentina Rigo ◽  
...  

The prognosis of children with metastatic neuroblastoma (NB) > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression ofCD45,CD14,ARG1,CD163,CD4,FOXP3,Perforin-1(PRF1),Granzyme B (GRMB), andIL-10mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.). Children with high expression ofCD14,ARG1andFOXP3mRNA in their primary tumors had significantly better EFS. Elevated expression ofCD14, andFOXP3mRNA was significantly associated to better OS.CD14mRNA expression levels significantly correlated to all markers, with the exception ofCD4. Strong positive correlations were found betweenPRF1andCD163, as well as betweenPFR1andFOXP3. It is worth noting that the combination of high levels ofCD14,FOXP3, andARG1mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels ofCD14were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinhui Liu ◽  
Rui Geng ◽  
Sheng Yang ◽  
Fang Shao ◽  
Zihang Zhong ◽  
...  

BackgroundUterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with low survival rate and poor prognosis. The traditional clinicopathological staging is insufficient to estimate the prognosis of UCEC. It is necessary to select a more effective prognostic signature of UCEC to predict the prognosis and immunotherapy effect of UCEC.MethodsCIBERSORT and weighted correlation network analysis (WGCNA) algorithms were combined to screen modules related to regulatory T (Treg) cells. Subsequently, univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the genes in key modules. The difference in overall survival (OS) between high- and low-risk patients was analyzed by Kaplan–Meier analysis. The Tregs-related risk signature (TRRS) was screened by uni- and multivariate Cox analyses. Afterward, we analyzed the expression difference of TRRS and verified its ability to predict the prognosis of UCEC and the effect of immunotherapy.ResultsRed module has the highest correlation with Tregs among all clustered modules. Pathways enrichment indicated that the related processes of UCEC were primarily associated to the immune system. Eight genes (ZSWIM1, NPRL3, GOLGA7, ST6GALNAC4, CDC16, ITPK1, PCSK4, and CORO1B) were selected to construct TRRS. We found that this TRRS is a significantly independent prognostic factor of UCEC. Low-risk patients have higher overall survival than high-risk patients. The immune status of different groups was different, and tumor-related pathways were enriched in patients with higher risk score. Low-risk patients are more likely take higher tumor mutation burden (TMB). Meanwhile, they are more sensitive to chemotherapy than patients with high-risk score, which indicated a superior prognosis. Immune checkpoints such as PD-1, CTLA4, PD-L1, and PD-L2 all had a higher expression level in low-risk group. TRRS expression really has a relevance with the sensitivity of UCEC patients to chemotherapeutic drugs.ConclusionWe developed and validated a TRRS to estimate the prognosis and reflect the immune status of UCEC, which could accurately assess the prognosis of patients with UCEC and supply personalized treatments for them.


2020 ◽  
Author(s):  
Yi Ding ◽  
Tian Li ◽  
Min Li ◽  
Tuersong Tayier ◽  
MeiLin Zhang ◽  
...  

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.


2010 ◽  
Vol 51 (3) ◽  
pp. 785
Author(s):  
P.A. Hansen ◽  
J.M.J. Richards ◽  
A.L. Tambyraja ◽  
L.R. Khan ◽  
R.T.A. Chalmers

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Rashid K. Sayyid ◽  
Diana Magee ◽  
Amanda E. Hird ◽  
Benjamin T. Harper ◽  
Eric Webb ◽  
...  

Introduction: Radical cystectomy (RC) is a highly morbid procedure, with 30-day complication rates approaching 31%. Our objective was to determine risk factors for re-operation within 30 days following a RC for non-metastatic bladder cancer. Methods: We included all patients who underwent a RC for non-metastatic bladder cancer using The American College of Surgeons National Surgical Quality Improvement Program database between January 1, 2007 and December 31, 2014. Logistic regression analyses were used to evaluate predictors of re-operation. Results: A total of 2608 patients were included; 5.8% of patients underwent re-operation within 30 days. On multivariable analysis, increasing body mass index (BMI) (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01–1.07), African-American race (vs. Caucasian OR 2.29; 95% CI 1.21–4.34), and history of chronic obstructive pulmonary disease (COPD) (OR 2.33; 95% CI 1.45–3.74) were significant predictors of re-operation within 30 days of RC. Urinary diversion type (ileal conduit vs. continent) and history of chemotherapy or radiotherapy within 30 days prior to RC were not. Patients who underwent re-operation within this timeframe had a significantly higher mortality rate (4.0% vs. 1.6%) and were more likely to experience cardiac (7.2% vs. 1.9%), pulmonary (23.0% vs. 3.0%), neurological (2.0% vs. 0.49%), and venous thromboembolic events (10.5% vs. 5.4%), as well as infectious complications (64.5% vs. 24.1%) with a significantly longer hospital length of stay (16.5 vs. 7.0 days). Conclusions: Recognizing increasing BMI, COPD, and African-American race as risk factors for re-operation within 30 days of RC will allow urologists to preoperatively identify such high-risk patients and prompt them to adopt more aggressive approaches to minimize postoperative surgical complications.


2015 ◽  
Vol 93 (6) ◽  
pp. 368-374
Author(s):  
Giuseppe Mucciardi ◽  
Luciano Macchione ◽  
Alessandro Galì ◽  
Antonina di Benedetto ◽  
Enrica Subba ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kelsey Ragan ◽  
Anjali Pandya ◽  
Tristan Holotnak ◽  
Katrina Koger ◽  
Neil Collins ◽  
...  

Background. Approximately 0.7% of the Canadian population is infected with hepatitis C virus (HCV), and many individuals are unaware of their infection. Our objectives were to utilize an emergency department (ED) based point-of-care (POC) HCV screening test to describe our local population and estimate the proportion of high-risk patients in our population with undiagnosed HCV. Methods. A convenience sample of medically stable patients (≥18 years) presenting to a community ED in Calgary, AB, between April and July 2018 underwent rapid clinical screening for HCV risk factors, including history of injection drug use, healthcare in endemic countries, and other recognized criteria. High-risk patients were offered POC HCV testing. Antibody-positive patients underwent HCV-RNA testing and were linked to hepatology care. The primary outcome was the proportion of new HCV diagnoses in the high-risk population. Results. Of the 999 patients screened by survey, 247 patients (24.7%) were high-risk and eligible for testing. Of these, 123 (49.8%) were from HCV-endemic countries, while 63 (25.5%) and 31 (12.6%) patients endorsed a history of incarceration and intravenous drug use (IVDU), respectively. A total of 144 (58.3%) eligible patients agreed to testing. Of these, 6 patients were POC-positive (4.2%, CI 0.9–7.4%); all 6 had antibodies detected on confirmatory lab testing and 4 had detectable HCV-RNA viral loads in follow-up. Notably, 103 (41.7%) patients declined POC testing. Interpretation. Among 144 high-risk patients who agreed to testing, the rate of undiagnosed HCV infection was 4.2%, and the rate of undiagnosed HCV infection with detectable viral load was 2.8%. Many patients with high-risk clinical criteria refused POC testing. It is unknown if tested and untested groups have the same disease prevalence. This study shows that ED HCV screening is feasible and that a small number of previously undiagnosed patients can be identified and linked to potentially life-changing care.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3332-3332
Author(s):  
Dawn S. Speckhart ◽  
H.K. Holland ◽  
Scott R. Solomon ◽  
Lawrence E. Morris ◽  
Asad Bashey

Abstract Several studies have begun to examine the relationship between psychosocial variables and outcome in hematopoietic stem cell transplantation (HSCT). Data presented at the 2006 ASH Convention, demonstrated a significant relationship between psychosocial variables, such as those assessed on the Transplant Evaluation Rating Scale (TERS), and objective outcomes, such as length of hospitalization and survival. The 2006 data included 200 consecutive patients (136 autologous, 65 allogeneic) undergoing HSCT. Based on the patient’s TERS score, each patient was stratified into one of two groups (low/moderate risk (n=173) vs. high risk (n=28)) based on their predicted psychosocial risk for problems during transplant. With the addition of 166 patients (Current N=366: 239 autologous, 127 allogeneic) the difference in length of hospitalization between low/moderate risk (10 days) versus high risk (19 days) patients remains significant (p<.02). For allogeneic patients (N=127), there continues to be an improved overall survival in low/moderate risk patients in the first 12 to 18 months following HSCT compared to high risk patients (p = .246). To determine whether similar factors impact utilization of resources in patients undergoing HSCT, we prospectively conducted psychosocial assessments on 112 consecutive allogeneic HSCT patients. An analysis of cost was completed for all patients in both the low/moderate risk group and high risk group. The mean cost differential for high risk patients is noted to be 27% higher than those patients in the low/moderate risk group (p = .122). This trend reinforces earlier data presented and suggests a correlation between pre-transplant psychosocial risk factors and resource utilization in HSCT. Overall Survival Overall Survival


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 874-874
Author(s):  
Fausto R Loberiza ◽  
Anthony J Cannon ◽  
Dennis D Weisenburger ◽  
Julie M. Vose ◽  
Matt J. Moehr ◽  
...  

Abstract Objectives: We evaluated the association of the primary area of residence (urban vs. rural) and treatment (trt) provider (university-based vs. community-based) with overall survival in patients with lymphoma, and determined if there are patient subgroups that could benefit from better coordination of care. Methods: We performed a population-based study in 2,330 patients with centrally confirmed lymphoma from Nebraska and surrounding states reported to the Nebraska Lymphoma Study Group between 1982 and 2006. Patient residential ZIP codes at the time to trt were used to determine rural/urban designation, household income and distance to trt center; while trt providers were categorized into university-based or community based. Multivariate analyses were used to group patients into risk levels based on 8 factors found to be associated with survival at the time of trt (age, performance score, Ann Arbor stage, presence of B symptoms, LDH levels, tumor bulk, nodal and extranodal involvement). The following categories were identified: low-risk (1–3 factors), intermediate risk (4–5 factors), and high-risk (≥6 factors). Cox proportional regression analyses, stratified by type of lymphoma (low-grade NHL, high-grade NHL and Hodgkin) were used to evaluate the association between place of residence and trt provider with overall survival. Results: Among urban residents, 321 (14%) were treated by university-based providers (UUB) and 816 (35%) were treated by community-based providers (UCB). Among rural residents, 332 (14%) were treated by university-based providers (RUB) and 861 (37%) were treated by community-based providers (RCB). Patients from rural areas were more likely to be older and Caucasian, with a lower median household income, greater travel distance to seek trt, and more likely to have high-risk disease when compared to patients from urban areas. In multivariate analysis, using all patients regardless of risk level, the relative risk of death (RR) among UUB, UCB and RUB was not statistically different. However, RCB had a higher risk of death RR 1.37, 95% CI 1.14–1.65, p=0.01; RR 1.18, 95% CI 1.04–1.33, p<0.01; and RR 1.26, 95% CI 1.06–1.49, p=0.01 when compared with UUB, UCB and RUB, respectively. This association remained true in both low- and intermediate-risk patients. Among high-risk patients, both RUB and RCB were at higher risk of death when compared with UUB or UCB, while UCB were not different from UUB. We found no differences in progression-free survival according to place of residence and trt provider. The use of stem cell transplantation was significantly higher in patients coming from urban and rural areas treated by university-based providers (UUB 19%, RUB 16%) compared to urban and rural patients treated by community-based providers (UCB 11%, RCB 10%, p < 0.01). Patients from rural areas (RUB and RCB) were slightly less likely to die from lymphoma-related causes than patients from urban areas (75% versus 80%, p=0.04). Conclusion: Overall survival in patients with lymphoma is inferior in patients coming from rural areas. This relationship varies according to treatment provider and pretreatment risk levels. Further studies in patients from rural areas are needed to understand how coordination of care is carried to design appropriate interventions that may improve the disparity noted.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 170-170 ◽  
Author(s):  
Dieter Hoelzer ◽  
Andreas Huettmann ◽  
Felix Kaul ◽  
Sebastian Irmer ◽  
Nadja Jaekel ◽  
...  

Abstract Abstract 170 The effect of Rituximab in conjunction with a chemo induction and consolidation therapy was studied in CD20+, Ph/BCR-ABL negative B-precursor ALL (Pre-B/Common) in the GMALL Study 07/2003. The rationale were encouraging results with combined intensive chemotherapy and Rituximab in CD20+ adult Burkitt lymphoma / leukemia. Furthermore that in previous GMALL studies, improvement of B-precursor ALL by intensification of chemotherapy was limited and the observation that patients with CD20+ cells (antigen expression >20%) had an inferior outcome in adult ALL (Thomas et al. Blood 2009. 113;6330). Aim: In standard risk (SR) patients the aim was to increase the rate of molecular remission (Mol. CR) thereby decreasing the relapse rate and in high risk (HR) patients to reduce the pre-transplant tumour-load and thereby reducing the relapse rate after SCT which was 30–40% in previous GMALL studies. Materials and Methods: Adult ALL patients (15 – 55 years) with standard risk B-precursor ALL being CD20 pos. received Rituximab 375 mg/m2 at day -1 before each induction course (phase I and II), the re-induction course and before each of the six consolidations for a total of 8 doses. High Risk patients, defined as WBC > 30.000 and/or late CR > 4 weeks, which are candidates for a stem cell transplantation in CR 1 after wk 16, received Rituximab three times (d -1 ind. I/II and Cons. I) before SCT. Patients receiving Rituximab were compared with earlier CD20+ patients in the GMALL study 07/2003 with identical chemo- and supportive therapy but no Rituximab. MRD method and chemo backbone was described earlier [Brüggemann, Blood 2006: 107;1116]. Results: A total of 263 CD20 pos. patients were analyzed in the GMALL study 07/2003; 196 were SR and 67 HR patients. 181 received Rituximab (R+ arm) and were compared to a cohort of 82 patients earlier recruited without Rituximab (R- arm). In the SR there was no difference in the results of induction therapy with a CR rate of 94 % and 91 % in the R+ vs. R- patients. There was also no difference in ED rate 5% vs. 3% or failure/PR 1% vs. 5%. However, MRD course differed substantially. Decrease in MRD load in the R+ vs. R- arm was faster with a Mol CR (MRD <10-4) rate of 57% vs. 27% at day 24 and of 90% vs. 59% at wk 16. Probability for continuous complete remission (CCR) at 5 years was 80% vs. 47% for R+ vs. R- pts. and for overall survival 71% vs. 57%. In the cohort of 67 HR patients the CR rate for R+ vs. R- was 81% vs. 88% due to a higher rate of failure/PR 12% vs. 8%. The ED rates in the R+ vs. R- arm were 7% vs. 4%. There was a higher Mol CR rate at wk 16 in the R+ arm vs. R- with 64% vs. 40%. Overall survival for HR patients at 5 yrs was 55% vs. 36% in the R+ vs. R- group. When only the HR cohort with SCT in CR1 is considered (in 69 % +R and 90% -R SCT in CR1 were performed) the CCR probability was superior for the R+ vs. R- with 67% vs. 37%, due to a lower relapse rate. Conclusion: Intensive chemo- plus immunotherapy with Rituximab is feasible in adult patients with B-precursor ALL in the context of the GMALL protocol 07/2003. In standard risk patients, the complete remission rate was comparable. There was however a faster and higher Mol. CR rate in the Rituximab cohort, with an improvement in remission duration and overall survival. In high risk patients the Mol. CR rate was also higher in the R+ arm and the relapse rate after SCT lower, but probably more Rituximab doses are needed in this patient cohort to reduce the tumour load before SCT further. Supported by Deutsche Krebshilfe 70–2657-Ho2 and in part by Hoffmann La Roche. Disclosures: Off Label Use: Rituximab: activity against CD20 pos. ALL cells.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3088-3088
Author(s):  
Ryan A. Wilcox ◽  
Kay Ristow ◽  
Thomas M. Habermann ◽  
David James Inwards ◽  
Ivana Micallef ◽  
...  

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.


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