scholarly journals A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Anli Yang ◽  
Minqing Wu ◽  
Mengqian Ni ◽  
Lijuan Zhang ◽  
Mingyue Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Scoring System ◽  
Triple Negative ◽  
Validation Cohort ◽  
Risk Group ◽  
Training Cohort ◽  
Risk Scoring ◽  
Risk Scoring System

Abstract The tumor microenvironment (TME) interacting with the malignant cells plays a vital role in cancer development. Herein, we aim to establish and verify a scoring system based on the characteristics of TME cells for prognosis prediction and personalized treatment guidance in patients with triple-negative breast cancer (TNBC). 158 TNBC samples from The Cancer Genome Atlas (TCGA) were included as the training cohort, and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), as well as GSE58812 (N = 107), were included as the validation cohort. The enrichment scores of 64 immune and stromal cells were estimated by the xCell algorithm. In the training cohort, cells with prognostic significance were found out using univariate Cox regression analysis and further applied to the random survival forest (RSF) model. Basing on the scores of M2 macrophages, CD8+ T cells, and CD4+ memory T cells, a risk scoring system was constructed, which divided TNBC patients into 4 phenotypes (M2low, M2highCD8+ThighCD4+Thigh, M2highCD8+ThighCD4+Tlow, and M2highCD8+Tlow) and 2 groups. The low-risk group had superior survival outcomes than the high-risk one, which was further confirmed in the validation cohort. Moreover, in the low-risk group, immune-related pathways were significantly enriched, and a higher level of antitumoral immune cells and immune checkpoint molecules, including PD-L1, PD-1, and CTLA-4, could be observed. Additionally, consistent results were achieved in the SYSUCC cohort when the scoring system was applied. In summary, this novel scoring system might predict the survival and immune activity of patients and might serve as a potential index for immunotherapy.

scholarly journals Immune Score-based Molecular Subtypes and Signature Associated with Clinical Outcome in Hepatoblastoma

2021 ◽  
Vol 21 (9) ◽  
Author(s):  
Yongping Huang ◽  
Jinlong Yan ◽  
Ruiqi Liu ◽  
Guang Tang ◽  
Qi Dong ◽  
...  
Keyword(s):  
T Cells ◽  
Scoring System ◽  
Prognostic Value ◽  
Molecular Subtypes ◽  
Risk Group ◽  
Molecular Subtype ◽  
Gene Signature ◽  
Risk Scoring ◽  
Immune Score ◽  
Risk Scoring System

Background: This study aimed to identify genes related to the immune score of hepatoblastoma, examine the characteristics of the immune microenvironment of hepatoblastoma, and construct a risk scoring system for predicting the prognosis of hepatoblastoma. Methods: Through using the gene chip data of patients with hepatoblastoma with survival data in the ArrayExpress and GEO databases, the immune score of hepatoblastoma was calculated by the ESITIMATE algorithm, and the prognostic value of immune score in patients with hepatoblastoma was studied by the survival analysis. Genes related to the immune score were identified by the WGCNA algorithm. According to these genes, patients with hepatoblastoma were clustered unsupervised. Finally, the risk scoring system was constructed according to the immune score-related genes. Results: The immune score calculated by the ESTIMATE algorithm had a good prognostic value in patients with hepatoblastoma. Patients with high immune scores had better OS than those with low immune scores (P < 0.001). A total of 146 immune score-related genes were identified by WGCNA analysis, and univariate COX regression analysis indicated that 59 of the genes had prognostic value. According to the unsupervised clustering results of the 146 immune score-related genes, patients with hepatoblastoma could be divided into two subtypes with different prognoses, namely molecular subtype 1 and subtype 2, with molecular subtype 1 having a better prognosis. The immunocyte infiltration analysis results showed that the difference between the two subtypes was mainly in activated CD4 T cells, activated dendritic cells, CD56 bright natural killer cells, the macrophage, and regulatory T cells. According to the immune score-related genes, a risk scoring system was constructed based on a five-gene signature. After the cut-off value was determined, patients with hepatoblastoma were divided into a high-risk group and a low-risk group. The prognosis of the two groups was different. Conclusions: The immune score has a good prognostic value in patients with hepatoblastoma. Based on the different expression patterns of immune score-related genes, hepatoblastoma can be divided into two different prognostic molecular subtypes, showing different immunocyte infiltration patterns. The established risk scoring system based on a five-gene signature has a good predictive value in patients with hepatoblastoma.

scholarly journals Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

2021 ◽  
Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

Venous thromboembolism in psychogeriatric in-patients – A study of risk assessment, incidence, and current prophylaxis prescribing

2013 ◽  
Vol 25 (6) ◽  
pp. 913-917 ◽  
Author(s):  
Xinsheng Liu ◽  
Fintan O'Rourke ◽  
Huong Van Nguyen
Keyword(s):  
Risk Assessment ◽  
Venous Thromboembolism ◽  
Scoring System ◽  
Risk Group ◽  
Low Risk ◽  
Vte Prophylaxis ◽  
Retrospective Audit ◽  
Medium Risk ◽  
Risk Scoring ◽  
Risk Scoring System

ABSTRACTBackground: While venous thromboembolism (VTE) risk assessment and prophylaxis is well established for medical and surgical in-patients, there is a paucity of evidence, and therefore guidelines, in this area for psychogeriatric in-patients. We wished to determine VTE incidence, risk, and use of prophylaxis, in a psychogeriatric in-patient population.Methods: Retrospective audit of consecutive psychogeriatric patients aged 65 years and over admitted to Bankstown Hospital over a 3-year period, 2007–2009. Using an adapted VTE risk scoring system, patients were assigned as low, medium, or high VTE risk.Results: A total of 192 patients were included in the study. Mean age was 79.1 ± 7.0 years. Out of the total, 55.2% of patients had diagnosis of dementia, and 33.3% had depression. Overall, 81.8% (157/192) were assessed as low risk, and 18.2% (35/192) as medium risk. Also, 16.7% (32/192) received VTE prophylaxis.Four new VTE events occurred in medium-risk group, and one in low-risk group (p = 0.004). Overall VTE incidence was 10.5/10,000 patient-days, but 44.2 per 10,000 in medium-risk group. VTE risk score was predictive of VTE events – IRR 6.02 (95% Confidence Intervals (CI) = 1.76–20.7, p = 0.004) for every one-point increment in risk. Depression was associated with significantly higher VTE occurrence (6.3% in those with diagnosis vs. 0.8% without, p = 0.043).Conclusion: Using a VTE risk scoring system adapted for psychogeriatric in-patients, those assessed to be at medium risk had a significantly increased rate of VTE. On this basis, we would recommend VTE prophylaxis be prescribed for psychogeriatric in-patients assessed to be at medium and high level of risk.

scholarly journals Development and Validation of a New Risk Scoring System for Cancer Patients with Suspected Infection

2021 ◽  
Author(s):  
Bora Chae ◽  
Seonok Kim ◽  
Yoon-Seon Lee
Keyword(s):  
Cancer Patients ◽  
Scoring System ◽  
Validation Cohort ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Peripheral Oxygen Saturation ◽  
Suspected Infection ◽  
Risk Scoring ◽  
Risk Scoring System ◽  
New Scoring

Abstract Purpose: This study aimed to develop a new prognostic model for predicting 30-day mortality in cancer patients with suspected infection.Methods: This study is a retrospective cohort study and was conducted from August 2019 to December 2019 at a single center. Adult active cancer patients with suspected infection were enrolled among visitors to the emergency room (ER). Logistic regression analysis was used to identify potential predictors for a new model. Results: A total of 899 patients were included; 450 in the development cohort and 449 in the validation cohort. Six independent variables predicted 30-day mortality: Eastern Cooperative Oncology Group (ECOG) performance status (PS), peripheral oxygen saturation (SpO2), creatinine, bilirubin, C-reactive protein (CRP), and lactate. The C-statistic of the new scoring system was 0.799 in the development cohort and 0.793 in the validation cohort. The C-statistics in the development cohort was significantly higher than those of SOFA [0.723 (95% CI: 0.663–0.783)], qSOFA [0.596 (95% CI: 0.537–0.655)], and SIRS [0.547 (95% CI: 0.483–0.612)]. Conclusions: The discriminative capability of the new cancer-specific risk scoring system was good in cancer patients with suspected infection. The new scoring system was superior to SOFA, qSOFA, and SIRS in predicting mortality.

scholarly journals An 8-lncRNA Signature Predicts Survival of Triple-Negative Breast Cancer Patients Without Germline BRCA1/2 Mutation

2020 ◽  
Author(s):  
Minling Liu ◽  
Wei Dai ◽  
Mengyuan Zhu ◽  
Xueying Li ◽  
Shan Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Validation Cohort ◽  
Functional Enrichment ◽  
Biological Behavior ◽  
Risk Scores ◽  
Training Cohort

Abstract Background: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.Results:We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P=0.00018 and P =0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion.Conclusions: We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.

Risk scoring system for predicting axillary response after neoadjuvant chemotherapy in initially node-positive women with breast cancer

2018 ◽  
Vol 27 (2) ◽  
pp. 158-165 ◽  
Author(s):  
Lobna Ouldamer ◽  
Marie Chas ◽  
Flavie Arbion ◽  
Gilles Body ◽  
Julien Cirier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Scoring System ◽  
Node Positive ◽  
Risk Scoring ◽  
Risk Scoring System

scholarly journals Development And Validation of a Risk Scoring System to Predict Pneumothorax in CT-Guided Percutaneous Transthoracic Needle Biopsy

2021 ◽  
Author(s):  
Qiuhong Yang ◽  
Lin cheng Luo ◽  
Xinyi Peng ◽  
Hailong Wei ◽  
Qun Yi ◽  
...  
Keyword(s):  
Scoring System ◽  
Validation Cohort ◽  
Transthoracic Needle Biopsy ◽  
Ct Guided ◽  
Score System ◽  
Derivation Cohort ◽  
Risk Scoring ◽  
Risk Score System ◽  
Risk Scoring System ◽  
Percutaneous Transthoracic Needle Biopsy

Abstract Objective: To develop and validate a risk scoring system using variables easily obtained for the prediction of pneumothorax in CT-guided percutaneous transthoracic needle biopsy (PTNB).Methods: The derivation cohort was comprised of 1001 patients who underwent CT-guided PTNB. Multivariate logistic regression was used to identify risk factors for pneumothorax, which were treated as the foundation to develop the risk scoring system. To validate the system, a validation cohort group of 230 patients was enrolled.Results: Age, puncture times, puncture depth, smoking index, number of specimens, bleeding from the needle path, and lobular lesion were identified as risk factors in the derivation cohort. A risk scoring system (Hosmer-Lemeshow goodness-of-fit test p =0.33) was developed. The area under the receiver operating characteristic curve (AUROC) was 0.601 by using the risk score system. This risk score system demonstrated a better diagnostic effect with increasing age. In the group of patients older than 80 years, the AUROC was 0.76, showing good predictive power. This risk scoring system was confirmed in the validation cohort with an AUROC of 0.736.Conclusion: This scoring system has a good predictive effect in both derivation and validation cohort.

scholarly journals 789 Intratumoral plasmid IL-12 expands CD8+ T cells and induces a clinically validated CXCR3 signature in triple-negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A838-A838
Author(s):  
Erika Crosby ◽  
Hiroshi Nagata ◽  
Melinda Telli ◽  
Chaitanya Acharya ◽  
Irene Wapnir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Cd8 T Cells ◽  
Triple Negative ◽  
Intratumoral Injection ◽  
Interleukin 12 ◽  
Term Survival ◽  
Potential Biomarker

BackgroundTriple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Immune checkpoint inhibitors (ICI) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. Interleukin-12 (IL-12) is a pro-inflammatory cytokine involved in the generation of an inflammatory tumor microenvironment and is critical in eliciting a productive anti-tumor immune response. It has been investigated as an anti-cancer therapeutic using various delivery routes, but intratumoral injection of plasmid IL-12 (tavokinogene telseplasmid; tavo) followed by electroporation is a gene therapy approach with minimal systemic immune-related toxicity.MethodsIntratumoral injection of tavo was tested in several preclinical models of TNBC and single cell RNA sequencing (scRNAseq) was used to evaluate changes in the tumor microenvironment following treatment. These findings were then applied to the analysis of patient samples from a single arm, prospective clinical trial of tavo monotherapy (OMS-I140; NCT02531425).ResultsA comprehensive analysis of cellular networks using ligand-receptor interactions identified CXCR3 (expressed by APCs) to be positively correlated with CXCL9/10/11 secreted by CD8 T cells. Further investigation of tavo treated murine tumors resulted in a 50-gene CXCR3 gene expression signature that is associated with a decrease in granulocytes, enhanced antigen presentation, increased T cell infiltration, and induction of PD-1/PD-L1. A deeper look at paired TCR alpha and beta chains on tumor infiltrating T cells (TILs) demonstrated a dramatic shift in TIL clonality and frequency following tavo treatment. There was a significant increase in not only the number of expanded (>10) clones, but also a robust activation signature that was absent in control tumors. Treatment of mice with tavo prior to anti-PD1 therapy led to complete tumor regression and long-term survival in a significant proportion of mice, while none of the mice treated with anti-PD1 alone exhibited this therapeutic efficacy. As a proof of concept, we utilized nanostring data from OMS-I140 to show a significant enhancement in this signature in patients who demonstrated a greater than 2-fold increase in CD8 TILS by IHC post-treatment. Further, we show a single patient who had previously been non-responsive to ICI that went on to receive anti-PD1 as their immediate next treatment after participating in OMS-I140, and demonstrated a significant clinical response.ConclusionsTogether these data identify a clinically relevant CXCR3-associated gene signature that represents both a potential biomarker for response to ICIs and a potentially targetable pathway for therapeutic intervention in TNBC.Ethics ApprovalAll animal studies described were approved by the Duke University Medical Center Institutional Animal Care & Use Committee (A198-18-08) and performed in accordance with established guidelines.

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