scholarly journals The Prognostic Role of m6A-Related Genes in Paediatric Neuroblastoma Patients

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Chunyang Zhang ◽  
Zhaozheng Ding ◽  
Hong Luo
Keyword(s):  
Gene Expression ◽  
Prognostic Factors ◽  
Operating Characteristic ◽  
Risk Model ◽  
Disease Free Survival ◽  
Roc Curves ◽  
Risk Groups ◽  
Prognostic Role ◽  
Target Database

Background and Purpose. N6-Methyladenosine (m6A) is the most abundant methylation modification form in eukaryotic mRNA. Nonetheless, the role of m6A-related genes in neuroblastoma (NB) is unclear. This study attempted to determine the prognostic role of m6A-related genes in NB patients. Methods. The gene expression data were extracted from the “Therapeutically Applicable Research to Generate Effective Treatments” (TARGET) database. The differentially expressed genes (DEGs) were identified, and the relationships between DEGs and m6A genes were explored. Then, the correlations among the m6A genes in neuroblastoma were investigated. Finally, the prognostic role of the m6A genes was studied, and the risk model was constructed. Results. 81 NB patients were extracted from the TARGET database. After comparing the gene expression between unfavorable and favorable outcome groups, 73 DEGs were identified, including 54 downregulated genes and 19 upregulated genes. In NB patients, we found that IGF2BP3, METTL14, and METTL16 are prognostic factors for disease-free survival (DFS) while IGF2BP3, METTL14, and METTL16 are prognostic factors for overall survival (OS). Besides, after the risk model construction, the OS between the two risk groups was drawn (log-rank p = 1.64 e − 08 , HR = 3.438 , 95% CI 2.24-5.278). The 1-, 3-, and 5-year time-dependent receiving operating characteristic (ROC) curves were also illustrated, and the areas under the receiver operating characteristic curves (AUCs) attained 0.75, 0.798, and 0.768, respectively. Conclusions. IGF2BP3, METTL14, and METTL16 were identified as the significant factors for DFS and OS in NB patients.

scholarly journals N6-methyladenosine-related non-coding RNAs are potential prognostic and immunotherapeutic responsiveness biomarkers for bladder cancer

2021 ◽  
Author(s):  
Miaolong Lu ◽  
Hailun Zhan ◽  
Bolong Liu ◽  
Dongyang Li ◽  
Wenbiao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Prognostic Factors ◽  
Risk Model ◽  
Clinical Stage ◽  
Risk Groups ◽  
Lasso Regression ◽  
Prognostic Evaluation ◽  
Non Coding Rnas ◽  
Tcga Dataset

Abstract Background Bladder cancer (BC) is a commonly occurring malignant tumor of the urinary system, demonstrating high global morbidity and mortality rates. BC currently lacks widely accepted biomarkers and its predictive, preventive, and personalized medicine (PPPM) is still unsatisfactory. N6-methyladenosine (m6A) modification and non-coding RNAs (ncRNAs) have been shown to be effective prognostic and immunotherapeutic responsiveness biomarkers and contribute to PPPM for various tumors. However, their role in BC remains unclear. Methods m6A-related ncRNAs (lncRNAs and miRNAs) were identified through a comprehensive analysis of TCGA, starBase, and m6A2Target databases. Using TCGA dataset (training set), univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop an m6A-related ncRNA–based prognostic risk model. Kaplan-Meier analysis of overall survival (OS) and receiver operating characteristic (ROC) curves were used to verify the prognostic evaluation power of the risk model in the GSE154261 dataset (testing set) from Gene Expression Omnibus (GEO). A nomogram containing independent prognostic factors was developed. Differences in BC clinical characteristics, m6A regulators, m6A-related ncRNAs, gene expression patterns, and differentially expressed genes (DEGs)–associated molecular networks between the high- and low-risk groups in TCGA dataset were also analyzed. Additionally, the potential applicability of the risk model in the prediction of immunotherapeutic responsiveness was evaluated based on the “IMvigor210CoreBiologies” data set. Results We identified 183 m6A-related ncRNAs, of which 14 were related to OS. LASSO regression analysis was further used to develop a prognostic risk model that included 10 m6A-related ncRNAs (BAALC-AS1, MIR324, MIR191, MIR25, AC023509.1, AL021707.1, AC026362.1, GATA2-AS1, AC012065.2, and HCP5). The risk model showed an excellent prognostic evaluation performance in both TCGA and GSE154261 datasets, with ROC curve areas under the curve (AUC) of 0.62 and 0.83, respectively. A nomogram containing 3 independent prognostic factors (risk score, age, and clinical stage) was developed and was found to demonstrate high prognostic prediction accuracy (AUC = 0.83). Moreover, the risk model could also predict BC progression. A higher risk score indicated a higher pathological grade and clinical stage. We identified 1058 DEGs between the high- and low-risk groups in TCGA dataset; these DEGs were involved in 3 molecular network systems, i.e., cellular immune response, cell adhesion, and cellular biological metabolism. Furthermore, the expression levels of 8 m6A regulators and 12 m6A-related ncRNAs were significantly different between the two groups. Finally, this risk model could be used to predict immunotherapeutic responses. Conclusion Our study is the first to explore the potential application value of m6A-related ncRNAs in BC. The m6A-related ncRNA–based risk model demonstrated excellent performance in predicting prognosis and immunotherapeutic responsiveness. Based on this model, in addition to identifying high-risk patients early to provide them with focused attention and targeted prevention, we can also select beneficiaries of immunotherapy to deliver personalized medical services. Furthermore, the m6A-related ncRNAs could elucidate the molecular mechanisms of BC and lead to a new direction for the improvement of PPPM for BC.

scholarly journals A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wanting Song ◽  
Yi Bai ◽  
Jialin Zhu ◽  
Fanxin Zeng ◽  
Chunmeng Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Critical Function ◽  
Mesenchymal Transition ◽  
Patient Prognosis

Abstract Background Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

scholarly journals Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC

2020 ◽  
Author(s):  
Toshiaki Iwase ◽  
Kenichi Harano ◽  
Hiroko Masuda ◽  
Kumiko Kida ◽  
Kenneth R. Hess ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Survival Outcome ◽  
Stage Iii ◽  
Prognostic Role ◽  
Poor Survival ◽  
Poor Survival Outcome

Abstract Purpose: The purpose of this study was to determine the prognostic role of hormone receptor (HR) on inflammatory breast cancer (IBC) to elucidate its aggressive biological behavior.Methods: We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemical staining and determined the predictive and prognostic role of HR expression on 189 patients with HR+/HER2– IBC and 677 patients with HR+/HER2– stage III non-IBC. Furthermore, we performed gene expression (GE) analyses for 137 patients with HR+/HER2– IBC and 252 patients with corresponding non-IBC to detect genes that are specifically overexpressed in IBC.Results: The expression of ER% was significantly associated with longer distant disease-free survival and overall survival. However, there was no significant relationship between ER% and NAC outcome. In the GE study, 84 genes were identified as significantly distinguishing HR+ IBC from non-IBC. Among the top 15 canonical pathways expressed in IBC, the ERK/MAPK, PDGF, insulin receptor, and IL-7 signaling pathways were associated with the ER signaling pathway. Upregulation of the MYC gene was observed in three of these four pathways. Furthermore, HR+/HER2– IBC had significantly higher MYC amplification, and the genetic alteration was associated with poor survival outcome.Conclusions: Increased HR positivity was significantly associated with improved survival in both HR+/HER2– IBC and HR+/HER2– stage III non-IBC patients. HR+/HER2– IBC had several activated pathways with MYC upregulation, and the genetic alteration was associated with poor survival outcome. The results indicate that MYC may be a key gene for understanding the biology of HR+/HER2– IBC.

Prognostic Role of Estrogen Receptor Determination in Breast Cancer

1983 ◽  
Vol 69 (6) ◽  
pp. 527-530 ◽  
Author(s):  
Stefano Ciatto ◽  
Patrizia Bravetti ◽  
Gaetano Cardona ◽  
Luigi Cataliotti ◽  
Roberto Crescioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recent Literature ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Prognostic Role ◽  
Free Survival ◽  
The Difference ◽  
Disease Free ◽  
Actuarial Method

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N– cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N– cases should be reconsidered.

An Update on the Role of Thalidomide (THAL) in Total Therapy 2 (TT2) for Newly Diagnosed Patients with Multiple Myeloma (MM): Analysis of Subgroups Defined by Standard Prognostic Factors (SPF) and Gene Expression Profiling (GEP)-Derived Subgroups.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3389-3389 ◽  
Author(s):  
John D. Shaughnessy ◽  
Jeffrey Haessler ◽  
Jerry Zeldis ◽  
Yongsheng Huang ◽  
Fenghuang Zhan ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Risk Groups ◽  
Complete Response ◽  
Low Risk ◽  
Phase Iii ◽  
Significant Difference ◽  
And Control ◽  
Standard Risk

Abstract Background: THAL, whose activity in MM was discovered in the setting of advanced and refractory disease in the late 1990’s (Singhal, NEJM, 2000), has become the standard front-line therapy in combination with dexamethasone (DEX). In a randomized phase III tandem transplant trial, TT2, a higher complete response (CR) rate and longer event-free survival (EFS) had been observed on the THAL arm (Barlogie, NEJM, 2006). The similar overall survival (OS) on THAL and control arms had been attributed to the routine use of THAL as salvage therapy for the patients randomized to the No-THAL arm and the shorter post-relapse OS among patients randomized to the THAL arm. Patients and Methods: With a median follow-up on TT2 of 53mo, 107 patients have relapsed and 219 died. Subset analyses were performed to determine whether THAL confers an OS advantage in any subgroup of patients. Results: 6-yr EFS and OS rates are 48%/63% on THAL and 38%/58% on control arm (p=0.01/0.67). Post-relapse OS is now similar with median durations of 5.3mo/4.3mo among control/THAL arms (p=0.11). According to multivariate analyses of 11 standard prognostic factors, EFS was shorter among patients treated without THAL, in the presence of cytogenetic abnormalities (CA), B2M and LDH elevations and low albumin, whereas CR was favorable; OS was inferior with CA, high LDH, low albumin and in patients not receiving 2nd transplant or not achieving CR. Randomization to THAL was beneficial only in the >2 risk factor group: 6-yr OS was 47% in 31 patients on THAL and 12% in 31 control patients (Figure 1, p=0.01). When examined in the context of GEP (70 gene model-based high versus low risk groups) and inter-phase FISH data (amp1q21), available in 260 patients, the 57 with GEP low risk and absence of amp1q21 receiving THAL had 5-yr OS of 90% compared to 74% among 73 controls (p=0.13). Conclusion: With longer follow-up of 53mo on TT2, EFS remains superior among patients randomized to THAL; post-relapse survival is no longer inferior among those randomized to THAL; THAL benefited a high-risk subgroup with >2 standard risk factors, whereas no significant `difference has yet emerged among genetically defined subgroups. Figure Figure

Venous Thromboembolism Risk Model Predicts Early Progression and Overall Mortality in Cancer Patients Receiving Chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 172-172 ◽  
Author(s):  
Nicole M. Kuderer ◽  
Alok A. Khorana ◽  
Charles W. Francis ◽  
Eva Culakova ◽  
Thomas L. Ortel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Venous Thromboembolism ◽  
Disease Progression ◽  
Cancer Patients ◽  
Risk Score ◽  
Risk Model ◽  
Risk Groups ◽  
Group I ◽  
All Cause Mortality

Abstract Background: Venous Thromboembolism (VTE) is a common complication of cancer and is strongly associated with early all-cause mortality during the course of cancer chemotherapy (Kuderer et al. ASCO 2008). A clinical model for predicting the risk of VTE in cancer patients initiating chemotherapy has been recently developed and validated (Khorana et al. Blood 2008). Risk of VTE in low (group I), intermediate (group II) and high risk patients (group III) was 0.8%, 1.8% and 7.1%, respectively. The aim of current study is to evaluate the ability of the VTE risk model to predict disease progression and early all-cause mortality. Methods: A prospective study of 4,458 adult cancer patients with solid tumors or malignant lymphoma initiating a new chemotherapy regimen was conducted between 2002 and 2006 at 115 randomly selected practice sites throughout the USA. Demographic, clinical and treatment-related information was captured prospectively at baseline and during the first four cycles of chemotherapy, including rates of documented VTE, disease recurrence and deaths from all causes. Progression-free survival (PFS) and overall survival (OS) within 4 months of starting chemotherapy were estimated by the method of Kaplan-Meier and adjusted hazard ratios (HR ± 95% CI) were estimated by a Cox regression model, incorporating VTE as a time-dependent covariate. Results: Patient age ranged from 18–97 with a mean of 60 years. VTE occurred in 3% of patients by 4 months with a median of 38 days following initiation of chemotherapy. The HR for VTE occurrence among risk score groups II and III, compared to group I, were 3.07 [1.39–6.77] and 11.73 [5.22–16.37], (P<0.0001) respectively. Within 4 months, disease progression occurred in 298 patients and 137 patients died. Death or disease progression was reported in 7%, 18% and 28% of risk score groups I, II and III, respectively. HR for reduced PFS among risk groups II and III compared to group I were 2.77 [1.97–3.87] and 4.27 [2.90–6.27], respectively (P<0.0001). Death from all causes within 4 months of treatment initiation was reported in 1.2%, 5.9% and 12.7% patients for risk groups I, II and III. HR estimates for mortality among groups II and III were 3.56 [1.91–6.66] and 6.89 [3.50–13.57], respectively (P<0.0001). In multivariate analysis, the risk score and VTE occurrence were both significant independent predictors for early mortality and reduced PFS after adjusting for major prognostic factors including: age, stage, cancer type, ECOG performance status, Charlson comorbidity index, body mass index, relative dose intensity, and year of enrollment. Conclusions: VTE is strongly associated with increased early all-cause mortality during the course of cancer chemotherapy. A recently validated risk score is not only predictive of VTE occurrence, but also of progression-free and overall survival demonstrating a strong association with prognostic factors for disease progression and mortality.

Red Cell Distribution Width (RDW) at Diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL) Is Associated to Higher Mortality and Worse Overall Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5398-5398
Author(s):  
Leyre Bento ◽  
Juan Sarmentero ◽  
Ana Ortuño ◽  
Marta García-Recio ◽  
Bernardo Lopez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
High Risk ◽  
Roc Curves ◽  
Red Cell Distribution Width ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
Ecog Ps

Abstract Red cell distribution width (RDW) is an indicator of the variability in the size of circulating erythrocytes (anisocytosis); different conditions can increase the RDW levels; such as hemolysis, ineffective erythropoiesis and blood transfusions. Recently, different studies have shown an association between increased levels of RDW and inflammation in different diseases, being proposed as a surrogate marker of inflammation and a strong predictor of adverse outcome. The proposed mechanism of this association departs from the finding that Inflammatory cytokines like TNFand IL-6 (part of the classic inflammatory cascade), have been found to inhibit erythropoietin-induced erythrocyte maturation, which is reflected in the RDW increase. Some reports have found a relationship between RDW and mortality related to age or several malignant or non-malignant conditions. However, there is no information about the role of RDW in overall survival (OS) of patients with DLBCL. We aim to evaluate the prognostic role of RDW levels in DLBCL patients at diagnosis. METHODS We retrospectively evaluated 83 patients with DLBCL homogenously treated in frontline with R-CHOP from 2002 to 2013 in the Son Espases University Hospital. To avoid selection bias patients were obtained from Pharmacy and Pathology Departments registries. Main clinical and prognostic factors at diagnosis were obtained from medical records. Cheson criteria were used for response assessment. The RDW was collected from the hemogram at diagnosis. The IBM SPSS STADISTICS program was used for all statistical analyses. PFS (time to progression/relapse) and overall survival (OS) (time to death) were measured from the date of ABVD onset, and were estimated according to the Kaplan-Meier method. We performed the comparisons between those interest variables with the log-rank test. A comparison between categorical variables was made with the chi-square of Fisher's exact test, as appropriate. All reported P-values were two-sided, and statistical significance was defined at P<0.05. For selecting cutoff values in RDW we used ROC curves. RESULTS: Main characteristics of patients were as follows: median age was 62 (20-86) years, 24% had ECOG PS>1, 64% advanced III-IV Ann Arbor (AA) stage, 39% B-symptoms, 51% adjusted-International Prognostic Index (a-IPI) and 39% belong to the high risk (3-5) subgroups of R-IPI Median RDW was 14.6 (11.1-21.1). Using ROC curves we selected the cutoff 14.05 for the death event. We evaluated the association of increased RDW with main prognostic factors at diagnosis. RDW >14.05 at diagnosis was associated with a more advanced age, worse ECOG PS, a more advanced AA stage, higher incidence of B symptoms and IPI>2. However, RDW was not related to disease control in terms of response to therapy (p=0.39) or relapse/progression (p=0.21) rates. Inversely, RDW>14.05 was in fact associated to a higher mortality (47%) compared to only 17% in patients with RDW≤14.05 (p=0.008). Median follow-up was 77 (20-137) months. Univariate survival analysis showed age>60 years (p=0.001), ECOG PS>1 (p=0.036), high risk R-IPI (p=0.005), a higher than 15% reduction in relative dose-intensity (RDI) (p=0.026) and RDW>14.05 (p=0.008) were significantly related to worse OS. By contrast, RDW did not significantly influence progression-free survival (p=0.19). CONCLUSIONS: Higher RDW at diagnosis in this series of DLBCL patients was related with older age, worse ECOG PS and more advanced disease but this was not translated into a worse control of disease in terms of only a small non statistically significant impact in response or PFS. By contrast higher RDW was linked to a significantly higher mortality and worse OS possibly related to a higher proinflammatory basal status and comorbidities. Patients with higher RDW may be at risk of reduction in RDI. These findings could justify including RDW in scores of comorbidities in DLBCL as well as in other malignant and non-malignant conditions. Disclosures No relevant conflicts of interest to declare.

scholarly journals The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Yongping Zhang ◽  
Chaojie Liang ◽  
Yu Zhang ◽  
Zhinmin Wang ◽  
Ruihuan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Patients ◽  
Tumor Size ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
Tnm Stage ◽  
Potential Biomarker ◽  
Tcga Dataset

Abstract Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

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