scholarly journals Intratumoral Heterogeneity and Immune Response Indicators to Predict Overall Survival in a Retrospective Study of HER2-Borderline (IHC 2+) Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Gedmante Radziuviene ◽  
Allan Rasmusson ◽  
Renaldas Augulis ◽  
Ruta Barbora Grineviciute ◽  
Dovile Zilenaite ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Overall Survival ◽  
Tumor Microenvironment ◽  
Prognostic Value ◽  
Cox Regression ◽  
Intratumoral Heterogeneity ◽  
Prognostic Models ◽  
Spatial Entropy ◽  
Cd8 Cell

Breast cancer (BC) categorized as human epidermal growth factor receptor 2 (HER2) borderline [2+ by immunohistochemistry (IHC 2+)] presents challenges for the testing, frequently obscured by intratumoral heterogeneity (ITH). This leads to difficulties in therapy decisions. We aimed to establish prognostic models of overall survival (OS) of these patients, which take into account spatial aspects of ITH and tumor microenvironment by using hexagonal tiling analytics of digital image analysis (DIA). In particular, we assessed the prognostic value of Immunogradient indicators at the tumor–stroma interface zone (IZ) as a feature of antitumor immune response. Surgical excision samples stained for estrogen receptor (ER), progesterone receptor (PR), Ki67, HER2, and CD8 from 275 patients with HER2 IHC 2+ invasive ductal BC were used in the study. DIA outputs were subsampled by HexT for ITH quantification and tumor microenvironment extraction for Immunogradient indicators. Multiple Cox regression revealed HER2 membrane completeness (HER2 MC) (HR: 0.18, p = 0.0007), its spatial entropy (HR: 0.37, p = 0.0341), and ER contrast (HR: 0.21, p = 0.0449) as independent predictors of better OS, with worse OS predicted by pT status (HR: 6.04, p = 0.0014) in the HER2 non-amplified patients. In the HER2-amplified patients, HER2 MC contrast (HR: 0.35, p = 0.0367) and CEP17 copy number (HR: 0.19, p = 0.0035) were independent predictors of better OS along with worse OS predicted by pN status (HR: 4.75, p = 0.0018). In the non-amplified tumors, three Immunogradient indicators provided the independent prognostic value: CD8 density in the tumor aspect of the IZ and CD8 center of mass were associated with better OS (HR: 0.23, p = 0.0079 and 0.14, p = 0.0014, respectively), and CD8 density variance along the tumor edge predicted worse OS (HR: 9.45, p = 0.0002). Combining these three computational indicators of the CD8 cell spatial distribution within the tumor microenvironment augmented prognostic stratification of the patients. In the HER2-amplified group, CD8 cell density in the tumor aspect of the IZ was the only independent immune response feature to predict better OS (HR: 0.22, p = 0.0047). In conclusion, we present novel prognostic models, based on computational ITH and Immunogradient indicators of the IHC biomarkers, in HER2 IHC 2+ BC patients.

scholarly journals Identification of novel cell glycolysis related gene signature predicting survival in patients with breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Jiang ◽  
Chuyan Wu ◽  
Ming Wang ◽  
Ke Wei ◽  
Jimei Wang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Single Gene ◽  
Prediction Method ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Models ◽  
Normal Tissues ◽  
Predictive Risk

AbstractOne of the most frequently identified tumors and a contributing cause of death in women is breast cancer (BC). Many biomarkers associated with survival and prognosis were identified in previous studies through database mining. Nevertheless, the predictive capabilities of single-gene biomarkers are not accurate enough. Genetic signatures can be an enhanced prediction method. This research analyzed data from The Cancer Genome Atlas (TCGA) for the detection of a new genetic signature to predict BC prognosis. Profiling of mRNA expression was carried out in samples of patients with TCGA BC (n = 1222). Gene set enrichment research has been undertaken to classify gene sets that vary greatly between BC tissues and normal tissues. Cox models for additive hazards regression were used to classify genes that were strongly linked to overall survival. A subsequent Cox regression multivariate analysis was used to construct a predictive risk parameter model. Kaplan–Meier survival predictions and log-rank validation have been used to verify the value of risk prediction parameters. Seven genes (PGK1, CACNA1H, IL13RA1, SDC1, AK3, NUP43, SDC3) correlated with glycolysis were shown to be strongly linked to overall survival. Depending on the 7-gene-signature, 1222 BC patients were classified into subgroups of high/low-risk. Certain variables have not impaired the prognostic potential of the seven-gene signature. A seven-gene signature correlated with cellular glycolysis was developed to predict the survival of BC patients. The results include insight into cellular glycolysis mechanisms and the detection of patients with poor BC prognosis.

Retrospective Study about the Prevalence of (TILs) Tumor Infiltrating Lymphocytes in Non-Metastatic Triple Negative Breast Cancer Patients and its Prognostic Value

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hesham Ahmed ElGhazaly ◽  
Manal Mohamed El-Mahdy ◽  
Azza Mohamed Adel ◽  
Nermeen Mostafa ◽  
Aya Magdy Kamal Ali
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Free Survival ◽  
Female Patients ◽  
Risk Of Death ◽  
Reduced Risk

Abstract Background TNBC comprises a distinct disease entity with a unique microenvironment of TILs, the immunogenic potential of TNBC is derived from its genetic instability and high mutation rate. Tumors from patients with TNBC are more likely than tumors from patients with other subtypes to exhibit chromosomal instability and potential mutations. Objectives The study aims to evaluate the prevalence of CD8+ TILs biomarker by IHC in triple negative breast cancer and its prognostic value. TILs are an important prognostic value for the response of patient to chemotherapy the greater number of TILS is associated with higher probability of response to chemotherapy also decrease recurrence. TILS in triple negative breast cancer suggest a likely option for immunotherapy in this disease. Patients and Methods This is a retrospective study, which was carried on 30 female patients, Clinical data and paraffin wax block of female patients with triple negative breast cancer are to be collected from the breast cancer unit, department of clinical Oncology and Nuclear medicine Ain Shams university and Matarya teaching hospital. Results Several large systematic reviews and meta-analyses have confirmed that high levels of TILs are associated with better disease free survival and overall survival only in triple negative and HER2 positive subtypes, with no significant benefit seen in estrogen receptor positive breast carcinoma. In the Breast International Group (BIG) 02-98 trial shows that for every 10% increase in the intertumoral TILs there was a 17% reduced risk of relapse, and 27% reduced risk of death regardless of chemotherapy type. Also in eastern cooperative oncology group trial (ECOG) 2197, and 1199 showed that for every 10% increase in TILs, a 14% reduction of risk of recurrence, and 19% reduction in risk of death were observed. Conclusion Our study showed that All our patients (100%) were positive for CD8+, with a minimum range of 1% and a maximum range of 60%, most of the patients (20 patients) had CD8% between (10% to 20%). High levels of CD8 + TILs are good prognostic indicators in TNBC. our study showed that there were associations of CD8+ TILs infiltrate status with longer progression free survival and better overall survival in triple-negative breast cancer, but were not statistically significant probably due to our small sample size.

scholarly journals Bioinformatics-Based Identification of Tumor Microenvironment-Related Prognostic Genes in Pancreatic Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaojie Chen ◽  
Feifei Huang ◽  
Shangxiang Chen ◽  
Yinting Chen ◽  
Jiajia Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Tumor Microenvironment ◽  
Operating Characteristic ◽  
Cox Regression ◽  
Time Dependent ◽  
Concordance Index ◽  
Cox Regression Analysis ◽  
Score Model

ObjectiveGrowing evidence has highlighted that the immune and stromal cells that infiltrate in pancreatic cancer microenvironment significantly influence tumor progression. However, reliable microenvironment-related prognostic gene signatures are yet to be established. The present study aimed to elucidate tumor microenvironment-related prognostic genes in pancreatic cancer.MethodsWe applied the ESTIMATE algorithm to categorize patients with pancreatic cancer from TCGA dataset into high and low immune/stromal score groups and determined their differentially expressed genes. Then, univariate and LASSO Cox regression was performed to identify overall survival-related differentially expressed genes (DEGs). And multivariate Cox regression analysis was used to screen independent prognostic genes and construct a risk score model. Finally, the performance of the risk score model was evaluated by Kaplan-Meier curve, time-dependent receiver operating characteristic and Harrell’s concordance index.ResultsThe overall survival analysis demonstrated that high immune/stromal score groups were closely associated with poor prognosis. The multivariate Cox regression analysis indicated that the signatures of four genes, including TRPC7, CXCL10, CUX2, and COL2A1, were independent prognostic factors. Subsequently, the risk prediction model constructed by those genes was superior to AJCC staging as evaluated by time-dependent receiver operating characteristic and Harrell’s concordance index, and both KRAS and TP53 mutations were closely associated with high risk scores. In addition, CXCL10 was predominantly expressed by tumor associated macrophages and its receptor CXCR3 was highly expressed in T cells at the single-cell level.ConclusionsThis study comprehensively investigated the tumor microenvironment and verified immune/stromal-related biomarkers for pancreatic cancer.

scholarly journals Prognostic Biomarkers on a Competitive Endogenous RNA Network Reveals Overall Survival in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenxing Qin ◽  
Feng Qi ◽  
Jia Li ◽  
Ping Li ◽  
Yuan-Sheng Zang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Prognostic Model ◽  
Triple Negative ◽  
Cox Regression ◽  
Critical Role ◽  
Differentially Expressed ◽  
Cerna Network ◽  
Competitive Endogenous Rna

The objective of this study was to construct a competitive endogenous RNA (ceRNA) regulatory network using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with triple-negative breast cancer (TNBC) and to construct a prognostic model for predicting overall survival (OS) in patients with TNBC. Differentially expressed lncRNAs, miRNAs, and mRNAs in TNBC patients from the TCGA and Metabric databases were examined. A prognostic model based on prognostic scores (PSs) was established for predicting OS in TNBC patients, and the performance of the model was assessed by a recipient that operated on a distinctive curve. A total of 874 differentially expressed RNAs (DERs) were screened, among which 6 lncRNAs, 295 miRNAs and 573 mRNAs were utilized to construct targeted and coexpression ceRNA regulatory networks. Eight differentially expressed genes (DEGs) associated with survival prognosis, DBX2, MYH7, TARDBP, POU4F1, ABCB11, LHFPL5, TRHDE and TIMP4, were identified by multivariate Cox regression and then used to establish a prognostic model. Our study shows that the ceRNA network has a critical role in maintaining the aggressiveness of TNBC and provides comprehensive molecular-level insight for predicting individual mortality hazards for TNBC patients. Our data suggest that these prognostic mRNAs from the ceRNA network are promising therapeutic targets for clinical intervention.

Commission on Cancer CP3R Compliance Rates for Treatment of Patients With Triple Negative and HER2+ Breast Cancer: A National Cancer Database Analysis

2021 ◽  
pp. 000313482110516
Author(s):  
Srivarshini C. Mohan ◽  
Joshua Tseng ◽  
Marissa Srour ◽  
Alice Chung ◽  
Ashley Marumoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Quality Care ◽  
Private Insurance ◽  
National Cancer Database ◽  
Database Analysis ◽  
Her2 Breast Cancer ◽  
Academic Hospitals ◽  
Multi Agent

Background Cancer Program Practice Profile Reports (CP3R) metrics were released by the Commission on Cancer to provide standards for high-quality care. One metric is the recommendation of combination chemotherapy or chemo-immunotherapy (CIT) within 120 days of diagnosis for women under 70 with AJCC T1cN0M0 or Stage IB-III HER2+ or hormone receptor negative breast cancer ([Multi-agent chemotherapy] MAC). Our study assesses national concordance rates for MAC and CIT. Methods The National Cancer Database was queried from 2004-2014. Results 122,045 patients met criteria, of whom treatment for 101,800 (83.4%) patients was concordant with MAC and CIT. Treatment concordance increased from 75.7% in 2004 to 89.5% in 2014. For HER2+ patients, use of CIT treatment downtrended with progression of pathological stage, from 70.1% (stage I) to 58.1% (stage III). Mean overall survival of patients whose treatment was concordant with MAC and CIT was longer than that of patients who were non-concordant (146.6 vs 143.8 months, P <.01). On Cox regression, there was a survival benefit for concordant patients who were treated at academic hospitals (HR .89, 95% CI 0.802-.976) and had private insurance (HR .76, 95% CI 0.65-.89). Conclusion Compliance with MAC and CIT has improved over the past decade and is associated with a significant improvement in overall survival.

Resetting the tumor microenvironment to favor anti-tumor immunity after local ablation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2561-2561
Author(s):  
Corrine A. Nief ◽  
Júlia Sroda Agudogo ◽  
Alana Gonzales ◽  
Rebecca A. Previs ◽  
Smita K Nair ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Low Dose ◽  
Tumor Response ◽  
Surgical Excision ◽  
Tumor Ablation ◽  
Local Ablation

2561 Background: Percutaneous tumor ablation is a non-surgical method of tumor destruction that leaves necrotic tumor debris in situ. Tumor associated antigens released after ablation have the potential to initiate a systemic anti-tumor immune response, however the hostile tumor microenvironment hinders antigen presentation and T cell activity. We hypothesized that resetting the tumor microenvironment with oral sodium bicarbonate to decrease tumor acidity and low-dose cyclophosphamide to deplete pro-tumor immune cells would improve the ability of ablation to initiate anti-tumor immunity. Methods: Tumor growth, overall survival, and metastatic burden was assessed in orthotopic tumor models of triple-negative breast cancer (67NR, 4T1, and E0771). Tumor ablation was performed on palpable tumors using percutaneous ethanol injection (PEI) with 6% ethylcellulose to improve retention in the tumor. Surgical excision was used as a negative control to test the role of in situ tumor debris. Before ablation mice were placed on 200 mM of sodium bicarbonate (SB) in their drinking water and received a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CP). Mice surviving to 60 days after tumor implant without a primary tumor or signs of metastases were considered "cured" and re-challenged with 50e5 tumor cells in the contralateral mammary pad. T cell dependance was assessed with in vivo CD8 depletions. Results: The combination of PEI+SB+CP produced a potent anti-tumor response, curing a majority of mice (5/7 of E0771, 8/12 of 67NR, 7/12 of 4T1). No mice were cured using PEI alone, SB alone, CP alone, or any combination of two therapies (0/51 of E0771, 0/73 of 67NR, 0/75 of 4T1,). Re-challenge tumor growth was hindered in mice cured with PEI+SB+CP. Mice receiving PEI+SB+CP had significantly less metastases and lived longer than mice receiving surgical excision alone or surgical excision with SB+CP. Additionally the anti-metastatic response of PEI+SB+CP was undone when CD8+ T cells were depleted. Conclusions: Here the anti-tumor response of local ablation produced by PEI was enhanced by priming the tumor with low-dose CP and oral SB in metastatic breast cancer. These results suggest that tumor ablation with CP and SB can create a T cell dependent, personalized immune response to a tumor using only low-cost, easily accessible supplies, and the host’s own tumor.

Clinicopathological signature and prognostic value of RNA:m5C methyltransferases in gliomas

2020 ◽  
Author(s):  
Peng Wang ◽  
Kai Huang ◽  
Miaojing Wu ◽  
Qing Hu ◽  
Chuming Tao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Prognostic Value ◽  
Cox Regression ◽  
Roc Curves ◽  
Clinicopathological Features ◽  
Gene Set Enrichment Analysis ◽  
Consensus Clustering ◽  
Score Model ◽  
Genome Atlas

Abstract Background: Glioma is the most common primary intracranial tumor, accounting for the vast majority of intracranial malignant tumors. Aberrant expression of RNA:5-methylcytosine(m5C) methyltransferases has recently been the focus of research relating to the occurrence and progression of tumors. However, the prognostic value of RNA:m5C methyltransferases in glioma remains unclear. This study investigated RNA: m5C methyltransferase expression and defined its clinicopathological signature and prognostic value in gliomas. Methods: We systematically studied the RNA-sequence data of RNA:m5C methyltransferases underlying gliomas in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets and identified different subtypes using Consensus clustering analysis. Gene Ontology (GO) and Gene Set Enrichment analysis (GSEA) was used to annotate the function of these genes. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm analyses were performed to construct the risk score model. Kaplan-Meier method and Receiver operating characteristic (ROC) curves were used to assess the overall survival of glioma patients. Additionally, Cox proportional regression model analysis was developed to address the connections between the risk scores and clinical factors. Results: Consensus clustering of RNA:m5C methyltransferases identified three clusters of gliomas with different prognostic and clinicopathological features. Meanwhile, Functional annotations demonstrated that RNA:m5C methyltransferases were significantly associated with the malignant progression of gliomas. Thereafter, five RNA:m5C methyltransferase genes were screened to construct a risk score model which can be used to predict not only overall survival but also clinicopathological features in gliomas. ROC curves revealed the significant prognostic ability of this signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for glioma outcome. Conclusion: We demonstrated the role of RNA:m5C methyltransferases in the initiation and progression of glioma. We have expanded on the understanding of the molecular mechanism involved, and provided a unique approach to predictive biomarkers and targeted therapy.

miR-181 Expression is Associated With The Prognosis in Lung Cancer.

2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Suppressor Gene ◽  
Rank Test ◽  
High Morbidity ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Cancer Tissues

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.

Prognostic value of pretreatment MRI texture features in breast cancer brain metastasis treated with Gamma Knife radiosurgery

2020 ◽  
pp. 028418512095629
Author(s):  
Yingyan Zheng ◽  
Daoying Geng ◽  
Tonggang Yu ◽  
Wei Xia ◽  
Dejun She ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Gamma Knife ◽  
Prognostic Value ◽  
Gamma Knife Radiosurgery ◽  
Texture Features ◽  
Progression Free Survival ◽  
Target Lesion ◽  
Prognostic Models ◽  
Breast Cancer Brain Metastasis

Background Gamma Knife radiosurgery (GKS) was recommended for treating patients with breast cancer brain metastasis (BCBM), but predictions of the existing prognostic models for therapeutic responsiveness vary substantially. Purpose To investigate the prognostic value of pretreatment clinical, MRI radiologic, and texture features in patients with BCBM undergoing GKS. Material and Methods The data of 81 BCBMs in 44 patients were retrospectively reviewed. Progressive disease was defined as an increase of at least 20% in the longest diameter of the target lesion or the presence of new intracranial lesions on contrast-enhanced T1-weighted (CE-T1W) imaging. Radiomic features were extracted from pretreatment CE-T1W images, T2-weighted (T2W) images, and ADC maps. Cox proportional hazard analyses were performed to identify independent predictors associated with BCBM-specific progression-free survival (PFS). A nomogram was constructed and its calibration ability was assessed. Results The cumulative BCBM-specific PFS was 52.27% at six months and 11.36% at one year, respectively. Age (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.01–1.06; P = 0.004) and CE-T1W-based kurtosis (HR 0.72; 95% CI 0.57–0.92; P = 0.008) were the independent predictors. The combination of CE-T1W-based kurtosis and age displayed a higher C-index (C-index 0.70; 95% CI 0.63–0.77) than did CE-T1W-based kurtosis (C-index 0.65; 95% CI 0.57–0.73) or age (C-index 0.63; 95% CI 0.56–0.70) alone. The nomogram based on the combinative model provided a better performance over age ( P < 0.05). The calibration curves elucidated good agreement between prediction and observation for the probability of 7- and 12-month BCBM-specific PFS. Conclusion Pretreatment CE-T1W-based kurtosis combined with age could improve prognostic ability in patients with BCBM undergoing GKS.

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