Trends in conditional survival and predictors of late death in neuroblastoma.

10533 Background: Significant advances in the treatment of neuroblastoma have been made in the past several decades. There are scant data examining how these improvements have changed over time and differentially affected conditional survival among high- and non-high-risk patient groups. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results Database. We analyzed clinical characteristics and survival outcomes for 4717 neuroblastoma patients. Kaplan-Meier methods were used to estimate overall survival (OS) and conditional overall survival (COS) conditioned on having survived 1, 2, or 5 years from diagnosis, with estimates compared between groups using log-rank tests. Results: Five-year OS was 41.46% (95% CI 38.77-44.13) for the high-risk group and 91.13% (95% CI 89.49-92.53) for the non-high-risk group. Both groups saw significant improvements in OS by decade (p<0.001). Five-year COS among 1-year survivors was 52.69% (95% CI 38.77-44.13) for the high-risk group and 96.75% (95% CI 95.57-97.62) for the non-high-risk group. One-year survivors in the high-risk group showed a statistically significant improvement in COS over time. No difference in COS was observed among 5-year high-risk survivors. There were no statistically significant changes in COS over time for 1- and 5-year survivors in the non-high-risk group. In the high-risk and non-high-risk groups, 82% and 32% of late deaths (>5 years from diagnosis) were attributable to cancer, respectively. Statistically significant adverse prognostic factors for late death were age >1 year at diagnosis, metastatic disease, and non-thoracic primary site (p=0.001). Conclusions: Improvements in COS over time have largely benefited high-risk patients, though they are still at higher risk for late death due to cancer when compared to non-high-risk patients. Age, stage, and primary site, but not treatment decade, influence outcomes among 5-year survivors. [Table: see text]

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P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

European Heart Journal ◽

10.1093/eurheartj/ehz745.0468 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Grinberg ◽

T Bental ◽

Y Hammer ◽

A R Assali ◽

H Vaknin-Assa ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Cardiovascular Events ◽

Risk Group ◽

Temporal Trends ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

High Risk Patients ◽

Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

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A four-gene prognostic signature for predicting the overall survival of patients with lung adenocarcinoma

PeerJ ◽

10.7717/peerj.11911 ◽

2021 ◽

Vol 9 ◽

pp. e11911

Author(s):

Lei Liu ◽

Huayu He ◽

Yue Peng ◽

Zhenlin Yang ◽

Shugeng Gao

Keyword(s):

Overall Survival ◽

High Risk ◽

Lung Adenocarcinoma ◽

Prognostic Model ◽

Risk Group ◽

Gene Signature ◽

Tnm Staging ◽

High Risk Group ◽

Prognostic Signature ◽

Risk Patients

Background The prognosis of patients for lung adenocarcinoma (LUAD) is known to vary widely; the 5-year overall survival rate is just 63% even for the pathological IA stage. Thus, in order to identify high-risk patients and facilitate clinical decision making, it is vital that we identify new prognostic markers that can be used alongside TNM staging to facilitate risk stratification. Methods We used mRNA expression from The Cancer Genome Atlas (TCGA) cohort to identify a prognostic gene signature and combined this with clinical data to develop a predictive model for the prognosis of patients for lung adenocarcinoma. Kaplan-Meier curves, Lasso regression, and Cox regression, were used to identify specific prognostic genes. The model was assessed via the area under the receiver operating characteristic curve (AUC-ROC) and validated in an independent dataset (GSE50081) from the Gene Expression Omnibus (GEO). Results Our analyses identified a four-gene prognostic signature (CENPH, MYLIP, PITX3, and TRAF3IP3) that was associated with the overall survival of patients with T1-4N0-2M0 in the TCGA dataset. Multivariate regression suggested that the total risk score for the four genes represented an independent prognostic factor for the TCGA and GEO cohorts; the hazard ratio (HR) (high risk group vs low risk group) were 2.34 (p < 0.001) and 2.10 (p = 0.017). Immune infiltration estimations, as determined by an online tool (TIMER2.0) showed that CD4+ T cells were in relative abundance in the high risk group compared to the low risk group in both of the two cohorts (both p < 0.001). We established a composite prognostic model for predicting OS, combined with risk-grouping and clinical factors. The AUCs for 1-, 3-, 5- year OS in the training set were 0.750, 0.737, and 0.719; and were 0.645, 0.766, and 0.725 in the validation set. The calibration curves showed a good match between the predicted probabilities and the actual probabilities. Conclusions We identified a four-gene predictive signature which represents an independent prognostic factor and can be used to identify high-risk patients from different TNM stages of LUAD. A new prognostic model that combines a prognostic gene signature with clinical features exhibited better discriminatory ability for OS than traditional TNM staging.

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SPECIFICS OF ANTIHYPERTENSION THERAPY IN HYPERTENSIVES OF VARIOUS CARDIOVASCULAR RISK (BY THE REGISTRY OF CHRONIC NON-COMMUNICABLE DISEASES IN TYUMENSKAYA OBLAST)

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2018-3-4-10 ◽

2018 ◽

Vol 17 (3) ◽

pp. 4-10

Author(s):

A. Yu. Efanov ◽

Yu. A. Vyalkina ◽

Yu. A. Petrova ◽

Z. M. Safiullina ◽

O. V. Abaturova ◽

...

Keyword(s):

Cardiovascular Risk ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

Risk Level ◽

Moderate Risk ◽

High Risk Patients ◽

Risk Patients ◽

Very High

Aim. To assess the specifics of antihypertension therapy (AHT) in hypertensives of various cardiovascular risk, in the registry of chronic non-communicable diseases in Tyumenskaya oblast.Material and methods. A random sample studied, of 1704 patients with hypertension, inhabitants of Tyumenskaya oblast (region), ascribed to dispensary follow-up. Mean age 62±7,5 y.o. Of those 31,5% (n=537) males. The prevalence and efficacy of AHT assessed according to cardiovascular risk level. The significance was evaluated with the criteria χ2.Results. AHT was characterized by the growth of the frequency of treatment approaches with cardiovascular risk consideration. Regular treatment took 33,9% patients of low and moderate risk vs 41,3% of high and very high (p<0,01). In the male group such tendency also took place. Gender specifics of AHT was characterized by that in the groups of high and very high risk females took medications significantly more commonly than males — 46,6% vs 29,1% in high risk group (p<0,01) and 47,5% vs 30% in very high risk group (p<0,01). With the increase of the risk level, there was decline of treatment efficacy — from 95% in low risk group to 32,5% in very high risk group; 53,1% of the participants were taking monotherapy, 32,9% — two drugs, 14,0% — ≥3 drugs. With the increase of risk grade there is tendency to increase of combinational AHT, however with no significant increase of efficacy. Treatment efficacy in high and very high risk patients comparing to patients with low and moderate risk was significantly lower — 33,1% vs 69,7% (p<0,01), respectively. Statins intake among the high and very high risk patients was 10,6-11,0% males and 7,8% females (p<0,05).Conclusion. AHT in hypertensives in Tymenskaya oblast, under dispensary follow-up, is characterized by insufficient usage of combinational drugs. With the raise of cardiovascular risk there is tendency to higher rate of combinational AHT. However there is no significant increase in efficacy of treatment with the increase of medications number. A very low rate of statins intake is noted. The obtained specifics witness for the necessity to optimize AHT among the high and very high risk patients — inhabitants of Tyumenskya oblast.

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Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

BMC Medical Genomics ◽

10.1186/s12920-020-00819-5 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Eunjin Lee ◽

Ji Won Lee ◽

Boram Lee ◽

Kyunghee Park ◽

Joonho Shim ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Genomic Feature ◽

High Risk Patients ◽

Dna Mismatch ◽

Molecular Stratification ◽

Recurrent Mutations ◽

Risk Patients

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification. Methods Fifty-eight whole exome sequencing (WES) and forty-eight whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. Results In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients. Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

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Effects of the proportion of high-risk patients and control strategies on the prevalence of methicillin-resistant Staphylococcus aureus in an intensive care unit

BMC Infectious Diseases ◽

10.1186/s12879-019-4632-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Farida Chamchod ◽

Prasit Palittapongarnpim

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

High Risk ◽

Risk Group ◽

Control Strategies ◽

High Risk Group ◽

High Risk Patients ◽

Risk Patients ◽

Mrsa Infection ◽

And Control

Abstract Background The presence of nosocomial pathogens in many intensive care units poses a threat to patients and public health worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen endemic in many hospital settings. Patients who are colonized with MRSA may develop an infection that can complicate their prior illness. Methods A mathematical model to describe transmission dynamics of MRSA among high-risk and low-risk patients in an intensive care unit (ICU) via hands of health care workers is developed. We aim to explore the effects of the proportion of high-risk patients, the admission proportions of colonized and infected patients, the probability of developing an MRSA infection, and control strategies on MRSA prevalence among patients. Results The increasing proportion of colonized and infected patients at admission, along with the higher proportion of high-risk patients in an ICU, may significantly increase MRSA prevalence. In addition, the prevalence becomes higher if patients in the high-risk group are more likely to develop an MRSA infection. Our results also suggest that additional infection prevention and control measures targeting high-risk patients may considerably help reduce MRSA prevalence as compared to those targeting low-risk patients. Conclusions The proportion of high-risk patients and the proportion of colonized and infected patients in the high-risk group at admission may play an important role on MRSA prevalence. Control strategies targeting high-risk patients may help reduce MRSA prevalence.

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Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

10.21203/rs.3.rs-26131/v1 ◽

2020 ◽

Author(s):

Eunjin Lee ◽

Ji Won Lee ◽

Boram Lee ◽

Kyunghee Park ◽

Joonho Shim ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Genomic Feature ◽

High Risk Patients ◽

Dna Mismatch ◽

Recurrent Mutations ◽

Whole Transcriptome Sequencing ◽

Risk Patients

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification.Results Fifty-eight whole exome sequencing (WES) and 48 whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair (MMR) associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients.Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

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Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

10.21203/rs.3.rs-26131/v2 ◽

2020 ◽

Author(s):

Eunjin Lee ◽

Ji Won Lee ◽

Boram Lee ◽

Kyunghee Park ◽

Joonho Shim ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Genomic Feature ◽

High Risk Patients ◽

Dna Mismatch ◽

Molecular Stratification ◽

Recurrent Mutations ◽

Risk Patients

Abstract Background: MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification.Results: Fifty-eight whole exome sequencing (WES) and 48 whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair (MMR) associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients.Conclusions: This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

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CFAR, An Active Frontline Regimen for High-Risk Patients with CLL, Including Those with Del 17p.

Blood ◽

10.1182/blood.v112.11.2095.2095 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2095-2095 ◽

Cited By ~ 4

Author(s):

William G Wierda ◽

Susan M O’Brien ◽

Stefan H Faderl ◽

Alessandra Ferrajoli ◽

Charles Koller ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

Fish Analysis ◽

Color Flow ◽

High Risk Patients ◽

Significant Difference ◽

Risk Patients

Abstract High-risk patients (pts) with CLL can be identified by prognostic factors. Traditional prognostic factors that identify high-risk pts include Rai stage, absolute lymphocyte count (ALC), rapid lymphocyte doubling time, and serum beta-2 microglobulin (β2M). Del 17p is associated with loss of the tumor suppressor gene TP53. Patients with del 17p also tend to have mutations in TP53, thereby providing a second mechanism for complete TP53 knockout. Pts with del 17p have poor response to purine analogue-based treatments. β2M greater than twice the upper limit of normal (2XULN) was an independent high-risk feature for pts treated with the frontline fludarabine (F), cyclophosphamide (C), rituximab (R) regimen (FCR). Pts younger than 70 years with β2M >2XULN treated with FCR had a complete remission (CR) rate of 60% and median time to progression (TTP) of 70 months, compared to 84% and 86 months for pts <70 yrs old with β2M <2XULN. We evaluated the CFAR regimen (F 20mg/m2 d3–5; C 200mg/m2 d3–5; R 375–500mg/ m2 d2; and Alemtuzumab 30mg d1,3,5 of each 4-wk course) as frontline treatment in a high-risk group of pts with CLL. The trial completed planned enrollment of 60 pts; 48 are currently evaluable for response and follow-up. In this high-risk group, 28% of the 48 evaluable high-risk pts had del 17p prior to treatment by FISH analysis. Overall, the CR rate for the 48 pts was 69%, 54% CR for the 13 pts with del 17p. The overall response rates were 94% and 77% for the 48 pts and 13 pts with del 17p, respectively. CFAR was associated with more myelosuppression and fewer pts could receive all 6 intended courses compared with the historic high-risk group treated with FCR. However, a higher proportion of CFAR pts had no evidence of residual disease in the bone marrow by 2-color flow cytometry evaluation at response assessment. There is currently no difference in TTP or OS, comparing CFAR and FCR in this retrospective historical analysis with a short median follow-up time of 16 months for the CFAR group. There was no significant difference in incidence of infection during treatment with CFAR compared to FCR, with the exception of CMV reactivation. The CFAR regimen is active and tolerated in the highrisk group of pts with CLL, including those with del 17p. Follow-up continues for the pts treated on this trial in order to evaluate responses in all 60 enrolled pts and to evaluate time-to-event endpoints and compare with the historic FCR experience.

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A reclassification of Myelodysplastic Syndrome (MDS) patients of RAEB-1 subgroup according to IPSS-R improves discrimination of high risk patients and better predicts overall Survival. A retrospective analysis of 49 Patients

Blood ◽

10.1182/blood.v120.21.4957.4957 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4957-4957 ◽

Cited By ~ 1

Author(s):

Jaroslav Cermak ◽

Dana Mikulenková ◽

Jana Brezinova ◽

Kyra Michalova

Keyword(s):

Overall Survival ◽

High Risk ◽

Median Survival ◽

Risk Group ◽

Univariate Analysis ◽

Refractory Anemia ◽

Term Survival ◽

High Risk Patients ◽

Risk Patients ◽

Very High

Abstract Abstract 4957 Refractory anemia with excess of bone marrow (BM) blasts up to 10% (RAEB-1) has been generally considered a MDS subgroup with moderate prognosis and most of the patients are not indicated for immediate intensive treatment. In our retrospective study, 27 out of 49 patients with RAEB-1 had intermediate-1 (IM-1) risk and 22 patients were classified as intermediate-2 (IM-2) risk group according to the IPSS. Nevertheless, median survival of untreated patients with RAEB-1. was only 5. 0 months compared to 36. 3 months in untreated patients with ≤ 5% BM blasts at the time of diagnosis (P<0. 0001). After reclassification of patients according to revised IPSS (IPSS-R) only 14 patients remained in the intermediate (IM) risk group and 3 patients were even shifted to the low (L) risk group. On the other hand, 14 patients have fulfilled criteria for high (H) risk group and 18 out of 49 patients (37%) had very high (VH) risk score. Median survival of patients treated with low dose chemotherapy (9. 0 months) or hydroxyurea (8. 8 months) was not significantly different from that in patients who received supportive care only. A significant benefit in median survival was observed after combination chemotherapy (14. 0 months) or after stem cell transplantation (SCT) (17. 0 months). SCT was the only treatment connected with prolonged survival, nevertheless, estimated 5 years overall survival of 31. 2 months was significantly inferior (P=0. 02) to that of transplanted patients not only with ≤ 5% BM blasts (62. 2 months) but also with > 10% BM blasts (55. 6 months). Univariate analysis using Kaplan-Meier curves and log-rank2 test revealed as significant variables affecting overall survival: poor cytogenetics IPSS subgroup (P=0. 001), ECOG > 2 (P=0. 001), IM-2 IPSS risk group (P=0. 001), treatment with SCT (P=0. 003), platelet (PLT) count < 20×109/l (P=0. 004), high or very high IPSS-R risk group (P=0. 01) and age > 60 years (P=0. 03). The most important independent variable for determining overall survival (studied by Cox regression multivariate analysis) was poor cytogenetics according IPSS (P=0. 0001, χ2=52. 623), followed by PLT count < 20×109/l (P=0. 001, χ2= 10. 382), and ECOG > 2 (P=0. 002, χ2= 9. 794). Our data suggest that RAEB-1 represent a poor prognostic MDS subgroup with similar outcome as advanced MDS with > 10% BM blasts. The analysis confirms the usefulness of IPSS-R for prediction of survival and for better discrimination of high risk patients in subgroups of patients with less advanced disease. Moreover, the results of regression analysis justify the high scoring value of cytogenetic abnormalities used in IPSS-R. SCT represents the only treatment enabling a long-term survival of RAEB-1 patients, nevertheless, our results of SCT were inferior to that achieved in patients with advanced MDS. Thus, more extensive clinical trials validating efficiency of hypomethylating agents and other new drugs in the treatment of RAEB-1 patients are needed. Disclosures: No relevant conflicts of interest to declare.

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Multi-Omics Profiling Identifies Risk Hypoxia-Related Signatures for Ovarian Cancer Prognosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.645839 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xingyu Chen ◽

Hua Lan ◽

Dong He ◽

Runshi Xu ◽

Yao Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Poor Prognosis ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Cancer Prognosis ◽

High Risk Patients ◽

Risk Patients

BackgroundOvarian cancer (OC) has the highest mortality rate among gynecologic malignancy. Hypoxia is a driver of the malignant progression in OC, which results in poor prognosis. We herein aimed to develop a validated model that was based on the hypoxia genes to systematically evaluate its prognosis in tumor immune microenvironment (TIM).ResultsWe identified 395 hypoxia-immune genes using weighted gene co-expression network analysis (WGCNA). We then established a nine hypoxia-related genes risk model using least absolute shrinkage and selection operator (LASSO) Cox regression, which efficiently distinguished high-risk patients from low-risk ones. We found that high-risk patients were significantly related to poor prognosis. The high-risk group showed unique immunosuppressive microenvironment, lower antigen presentation, and higher levels of inhibitory cytokines. There were also significant differences in somatic copy number alterations (SCNAs) and mutations between the high- and low-risk groups, indicating immune escape in the high-risk group. Tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms showed that low-risk patients are significantly responsive to programmed cell death protein-1 (PD-1) inhibitors.ConclusionsIn this study, we highlighted the clinical significance of hypoxia in OC and established a hypoxia-related model for predicting prognosis and providing potential immunotherapy strategies.

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