scholarly journals Development of a tRNA-Derived Small RNA Prognostic Panel and Their Potential Functions in Osteosarcoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenming Tang ◽  
Shuhui Zhang ◽  
Zhougui Ling
Keyword(s):  
Small Rna ◽  
Target Genes ◽  
Cox Model ◽  
Expression Profiles ◽  
Survival Rates ◽  
Low Risk ◽  
Validation Dataset ◽  
Therapeutic Outcomes ◽  
Risk Patients ◽  
Geo Database

BackgroundTherapeutic outcomes of osteosarcoma treatment have not significantly improved in several decades. Therefore, strong prognostic biomarkers are urgently needed.MethodsWe first extracted the tRNA-derived small RNA (tsRNA) expression profiles of osteosarcoma from the GEO database. Then, we performed a unique module analysis and use the LASSO-Cox model to select survival-associated tsRNAs. Model effectiveness was further verified using an independent validation dataset. Target genes with selected tsRNAs were predicted using RNAhybrid.ResultsA LASSO-Cox model was established to select six prognostic tsRNA biomarkers: tRF-33-6SXMSL73VL4YDN, tRF-32-6SXMSL73VL4YK, tRF-32-M1M3WD8S746D2, tRF-35-RPM830MMUKLY5Z, tRF-33-K768WP9N1EWJDW, and tRF-32-MIF91SS2P46I3. We developed a prognostic panel for osteosarcoma patients concerning their overall survival by high-low risk. Patients with a low-risk profile had improved survival rates in training and validation dataset.ConclusionsThe suggested prognostic panel can be utilized as a reliable biomarker to predict osteosarcoma patient survival rates.

scholarly journals Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu
Keyword(s):  
Target Genes ◽  
Cox Regression ◽  
Expression Profiles ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Normal Mucosa ◽  
Microrna Expression ◽  
Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

A validated risk model for early neutropenic events in older cancer patients receiving systemic chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9036-9036 ◽  
Author(s):  
M. Shayne ◽  
E. Culakova ◽  
D. C. Dale ◽  
M. S. Poniewierski ◽  
D. A. Wolff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Predictive Value ◽  
Risk Model ◽  
Low Risk ◽  
Severe Neutropenia ◽  
Validation Dataset ◽  
Cancer Type ◽  
C Statistic ◽  
Risk Patients ◽  
Older Cancer Patients

9036 Background: A prospective, nationwide study was undertaken to develop and validate a risk model for early neutropenic events (NE) in older cancer patients undergoing chemotherapy. Methods: 1,386 patients =65 years of age with lung, breast, colorectal, ovarian cancer or lymphoma were prospectively registered at 117 randomly selected sites. Data on up to 4 cycles were collected upon initiation of chemotherapy. A logistic regression model for cycle 1 NE consisting of febrile neutropenia (FN; fever/infection and absolute neutrophil count nadir <1x109/L) or severe neutropenia (SN; neutrophils <.5x109/L) was derived on 1,378 patients with available data. Validation was performed using a split sample random selection process. Results: No significant differences in distribution of NE or predictive factors were observed between derivation dataset (n=922) and validation dataset (n=464). Major independent baseline clinical risk factors for cycle 1 NE in the derivation model (DM) included: anthracycline based regimens (p<.001), non-chemotherapy immune-modulatory agents (p=.003), elevated bilirubin (p=.016), reduced glomerular filtration rate (p<.001), cancer type (p=.02), planned relative dose intensity =85% (p=.027), and regimens containing cyclophosphamide (p<.001), etoposide (p=.002) or ifosfamide (p=.032). Reduced risk of cycle 1 NE was associated with myeloid growth factor (MGF) prophylaxis (p<.001). DM R2 was 0.478 and c-statistic 0.88 [95% CI 0.86–0.91; p<.001]. At median predicted risk of cycle 1 NE of 7%, model test performance (MTP) showed: sensitivity 90%; specificity 59%; and predictive value positive and negative of 32% and 97%, respectively. Cycle 1–4 FN risk in the DM was 16.6% and 3.3% among high and low risk patients, respectively. The validation model (VM) R2 was 0.508 and c-statistic 0.89 [95% CI: 0.86–0.93; p<.001]. MTP in the VM demonstrated: sensitivity 90%; specificity 65%; predictive value positive and negative of 36% and 97%, respectively. Cycle 1–4 FN risk in the VM was 16.8% and 1.6% in high and low risk patients, respectively. Conclusions: This validated risk model demonstrated good discrimination between older cancer patients at decreased risk for NE, and those at increased risk who may benefit from targeted prophylaxis with MGF. No significant financial relationships to disclose.

scholarly journals Identification and Clinical Validation of Genes Signatures With Grade and Survival in Head and Neck Carcinomas

2020 ◽  
Author(s):  
Wei Ma ◽  
Qing Cao ◽  
Wandong She
Keyword(s):  
High Risk ◽  
Head And Neck ◽  
Risk Score ◽  
Cox Regression ◽  
Expression Profiles ◽  
Low Risk ◽  
Low Grade ◽  
High Grade ◽  
Head And Neck Carcinomas ◽  
Risk Patients

Abstract Background: The mechanism of transition from low-grade to high-grade head and neck carcinomas (HNC) still remains unclear. The aim of this study was to explore the genes expression profiles that drive malignancy from low to high-grade HNC, as well as analyze their correlations with the survival.Methods: Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low and high-grade HNC were screened by GEO2R and R software. Bioinformatics functions of SDGs were investigated by the enrichment analyses. Univariate and multivariate cox regressions were performed to identify prognostic SDGs of progression free survival (PFS) and disease specific survival (DSS). ROC curve was established to evaluate the ability to predict the prognosis. Then, the correlations between SDGs and clinical features were evaluated. The genes were experimentally validated by RT-PCR in clinical specimens’ tissues at last.Results: Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Enrichment analysis showed these SDGs were mainly enriched in the DNA repair pathway and the regulation of I−kappaB kinase/NF−kappaB signaling pathway. Cox regression analyses showed that CXCL14, SLC44A1 and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients at a high-risk or low-risk for prognosis were established based on genes signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033, 0.010 respectively). Multivariate cox regression showed HPV (P=0.033), lymph node status (P=0.032) and residual status (P＜0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858, 0.901 respectively). In addition, we found UBD, PPP2R2C and risk score were significantly associated with HPV status (all P＜0.05). The experiment results showed CXCL14 and SLC44A1 were significantly overexpressed in the HNC grade I/II tissues and the UBD were overexpressed in the HNC grade III/IV tissues.Conclusions: Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarker to predict the survival.

Should adult medulloblastoma patients at low risk receive adjuvant chemotherapy? Long-term results of a prospective study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2018-2018
Author(s):  
E. Franceschi ◽  
A. Tosoni ◽  
M. Ermani ◽  
V. Blatt ◽  
P. Amistà ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Survival Rates ◽  
Low Risk ◽  
Long Term Results ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.

Identification of Patients At High Risk for Recurrent Venous Thromboembolism by Whole Blood Gene Expression Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2305-2305
Author(s):  
Thomas L. Ortel ◽  
Michele Beckman ◽  
W Craig Hooper ◽  
Deborah A Lewis ◽  
Jen-Tsan A. Chi ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Whole Blood ◽  
Antiphospholipid Antibodies ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Low Risk ◽  
Risk Patients ◽  
Patient Groups ◽  
Recurrent Vte

Abstract Abstract 2305 Background. Recurrent venous thromboembolism (VTE) occurs in ∼30% of patients with spontaneous VTE after completion of a standard course of anticoagulant therapy. D-dimer levels and selected clinical parameters have been used to identify patients at low risk for recurrent VTE, who may safely discontinue antithrombotic therapy. We have used gene expression profiles to distinguish patients with a single VTE from patients with recurrent VTE. The purpose of this study was to extend this initial report and identify unique gene expression patterns from whole blood that correlate with different risk profiles for VTE recurrence. Methods. Patients with ≥1 prior VTE, with the first event occurring at age 18 years or older and >3 months from the most recent event were recruited for this study. Patients were allocated into 4 groups: (1) ‘low-risk’ patients had sustained ≥1 provoked VTE; (2) ‘moderate-risk’ patients had sustained 1 unprovoked VTE (with or without provoked VTE); (3) ‘high-risk’ patients had sustained ≥2 unprovoked VTE and had no evidence for antiphospholipid antibodies; and (4) antiphospholipid syndrome (APS) patients met established consensus criteria for APS. A similar number of individuals with no prior history of VTE were enrolled as a control population. Citrated plasma, serum and PAXgene RNA tubes were collected, processed and stored at −80°C until shipped to the CDC for analysis. Antiphospholipid testing was performed on all participants to confirm correct group distribution. Total RNA was isolated from whole blood drawn into PAXgene tubes. Following sample labeling and normalization, cRNA samples were hybridized to Illumina HT-12 Beadchips to assay whole genome gene expression with over 47,000 probes against human transcripts. Two hundred and twenty six unique samples passed initial quality control measures. Quality assessment of raw data was done using GenomeStudio. The raw data files were converted to a text file using the IlluminaExpression FileCreator in GenePattern and then log transformed, normalized and median-centered using Cluster. Both unsupervised (hierarchical clustering using Cluster) and supervised analyses (SAM) were used to identify genes that were differentially expressed between the groups. GATHER was used to help understand the biological processes and gene ontology of the gene lists generated by Cluster and SAM. Results. A total of 226 participants were enrolled into the study. Characteristics of the patient groups are summarized in the Table. Demographically, the groups were similar except that patients in the high-risk group tended to be older and were more likely male. The number of events per patient, and the proportion on anticoagulant therapy, increased with the risk group. Antiphospholipid antibodies were detected in several patients in each of the 3 non-APS VTE patient groups, but in most cases this was a single test positive; antiphospholipid antibodies were present in the majority of patients with APS, typically with more than one test positive (37 of 45 with complete testing, 82%). Preliminary analysis of the gene expression profiles using an unsupervised clustering by gene on the high-risk and low-risk groups identified multiple genes that distinguished the two groups, including 18 immune response genes identified by GATHER. These two patient groups were also distinguished by SAM analysis, and multiple genes in the MAPK signaling pathway that separated the two groups were identified by the KEGG pathways in GATHER. Additional analyses are being performed on all of the groups. Conclusions. Whole blood gene expression profiling can be used to develop profiles that distinguish patients with VTE who differ based on their risk of recurrent events. Individual genes identified in these profiles may provide biological insights into the molecular basis for recurrent VTE. Disclosures: Heit: Daiichi Sankyo: Honoraria; Ortho-McNeil Janssen: Honoraria; Covidien: Honoraria. Manco-Johnson:Octapharma AG: Consultancy; Bayer: Research Funding.

scholarly journals Integrated small RNA and mRNA expression profiles reveal miRNAs and their target genes in response to Aspergillus flavus growth in peanut seeds

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chuanzhi Zhao ◽  
Tingting Li ◽  
Yuhan Zhao ◽  
Baohong Zhang ◽  
Aiqin Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Aspergillus Flavus ◽  
Small Rna ◽  
Target Genes ◽  
Expression Profiles

Identification of good and poor prognosis HPV associated oropharyngeal cancer based on CD103 immune cell expression in patients treated with cetuximab and radiotherapy on TROG 12.01 and De-ESCALaTE randomized trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 109-109
Author(s):  
Danny Rischin ◽  
Hisham Mohamed Mehanna ◽  
Richard J. Young ◽  
Mathias Bressel ◽  
Janet Dunn ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Immune Cell ◽  
Cox Model ◽  
Survival Rates ◽  
Symptom Burden ◽  
Stage Iv ◽  
Low Risk ◽  
Smoking History ◽  
Free Survival ◽  
Significant Difference

109 Background: Trials in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPVOPSCC), substituting cetuximab (CETUX) for cisplatin (CIS) with radiotherapy (RT), resulted in decreased efficacy without improved toxicity or symptom burden. We reported that high intratumoral immune cell (ITIC) CD103 expression (> 30%), a marker of tissue-resident memory T cells, is associated with better prognosis in unselected patients with HPVOPSCC treated with CIS/RT. In this study our aim was to determine whether low risk HPVOPSCC patients treated with CETUX/RT with high CD103 have a superior prognosis. Methods: TROG 12.01 and De-ESCALaTE are randomised multicentre trials that compared 70Gy RT/CETUX with 70Gy RT/CIS (weekly in TROG 12.01, 3-weekly in De-ESCALaTE) in patients with HPVOPSCC, low risk by Ang criteria: AJCC 7th Stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history > 10 pack years and/or distant metastases). In TROG 12.01 T4 and/or N3 patients were also excluded. Eligible patients required tumor samples available for immune cell quantification on immunohistochemistry. Data from the two trials were pooled, with analyses performed in eligible randomised patients who commenced treatment. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/ RT comparing CD103 ITIC > 30% (high) vs. < 30% (low). High/low CD103 were compared using Cox model adjusting for age, stage and trial. Results: Samples for CD103 testing were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. ITIC CD103 expression was high in 26% of patients. The median follow-up was 3.2 years. The 3 -year failure-free survival rates in patients treated with CETUX/RT were 92% (95% CI: 78-97%) in high CD103 and 74% (95% CI: 64-82%) in low CD103, adjusted HR 0.25 (95% CI: 0.14-0.44); p < 0.001. The 3 -year overall survival (OS) in patients treated with CETUX/RT were 100% in high CD103 and 86% (95% CI: 76-92%) in low CD103, p < 0.001. Superior FFS in the high CD103 group was independent of stage. In patients treated with CIS/RT there was no significant difference in FFS (3-year 86% in high CD103 and 90% in low CD103; p = 0.55) or in OS (3-year 100% in high CD103 and 95% in low CD103; p = 0.14). The increase in failures in the low CD103 patients treated with CETUX/RT was evenly split between distant and locoregional failures. Conclusions: ITIC CD103 separates CETUX/RT treated low risk HPVOPSCC into excellent and poor prognosis subgroups. In a low risk population CIS/RT achieves excellent outcomes in both high and low ITIC CD103 groups. The high ITIC CD103 population is a rational target for future de-intensification trials.

scholarly journals A 6-Gene Risk Signature Predicts Survival of Glioblastoma Multiforme

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jingwei Zhao ◽  
Le Wang ◽  
Guozhang Hu ◽  
Bo Wei
Keyword(s):  
Regression Analysis ◽  
Glioblastoma Multiforme ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Low Risk ◽  
Validation Dataset ◽  
Cox Regression Analysis ◽  
Genome Atlas

Background. This study aims to develop novel signatures for glioblastoma multiforme (GBM). Methods. GBM expression profiles from The Cancer Genome Atlas (TCGA) were downloaded and DEGs between tumor and normal samples were identified by differential expression analysis (DEA). A risk signature was developed by applying weighted gene coexpression network analysis (WGCNA) and Cox regression analysis. Patients were divided into high and low risk group, followed by evaluating the performance of the signature via Kaplan-Meier curve analysis. In addition, the prognostic significance of the signature was further validated using an independent validation dataset from Chinese Glioma Genome Atlas (CGGA). DEGs between high and low risk group were subjected to functional annotation. Results. A total of 748 DEGs were identified between primary tumor and normal samples. Following WGCNA and Cox regression analysis, 6 DEGs were identified and used to construct a risk signature. The signature showed high performance in both training and validation dataset. Subsequently, 397 DEGs were identified between high and low risk group. These DEGs were mainly enriched in terms related to calcium signaling, cAMP-mediated signaling, and synaptic transmission. Conclusions. The risk signature may contribute to GBM diagnosis in future clinical practice.

Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myélome

2008 ◽  
Vol 26 (29) ◽  
pp. 4798-4805 ◽  
Author(s):  
Olivier Decaux ◽  
Laurence Lodé ◽  
Florence Magrangeas ◽  
Catherine Charbonnel ◽  
Wilfried Gouraud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Multiple Myeloma ◽  
High Risk ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Low Risk ◽  
High Risk Patients ◽  
Risk Patients

Purpose Survival of patients with multiple myeloma is highly heterogeneous, from periods of a few weeks to more than 10 years. We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers. Patients and Methods In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival. A survival model was built from these genes. The validity of our model was assessed in our test set of 68 patients and in three independent cohorts comprising 853 patients with multiple myeloma. Results The 15 strongest genes associated with the length of survival were used to calculate a risk score and to stratify patients into low-risk and high-risk groups. The survival-predictor score was significantly associated with survival in both the training and test sets and in the external validation cohorts. The Kaplan-Meier estimates of rates of survival at 3 years were 90.5% (95% CI, 85.6% to 95.3%) and 47.4% (95% CI, 33.5% to 60.1%), respectively, in our patients having a low risk or high risk independently of traditional prognostic factors. High-risk patients constituted a homogeneous biologic entity characterized by the overexpression of genes involved in cell cycle progression and its surveillance, whereas low-risk patients were heterogeneous and displayed hyperdiploid signatures. Conclusion Gene expression–based survival prediction and molecular features associated with high-risk patients may be useful for developing prognostic markers and may provide basis to treat these patients with new targeted antimitotics.

scholarly journals In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2673
Author(s):  
YoungJoon Park ◽  
Jaekwang Jeong ◽  
Shin Seong ◽  
Wonnam Kim
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Information Gain ◽  
Therapeutic Potential ◽  
Expression Profiles ◽  
Survival Rates ◽  
Gene Expression Profiles ◽  
Natural Compounds ◽  
The Cancer Genome Atlas ◽  
Potential Candidate

The survival rates for breast cancer (BC) have improved in recent years, but resistance, metastasis, and recurrence still remain major therapeutic challenges for BC. The acidic tumor microenvironment (TME) has attracted attention because of its association with tumorigenesis, metastasis, drug resistance, and immune surveillance. In this study, we evaluated natural compounds from traditional herbal medicine used to treat cancer that selectively target genes regulated by extracellular acidosis. We integrated four transcriptomic data including BC prognostic data from The Cancer Genome Atlas database, gene expression profiles of MCF-7 cells treated with 102 natural compounds, patterns of gene profiles by acidic condition, and single-cell RNA-sequencing from BC patient samples. Bruceine D (BD) was predicted as having the highest therapeutic potential, having an information gain (IG) score of 0.24, to regulate reprogrammed genes driven by acidosis affecting the survival of BC patients. BD showed the highest IG on EMT (IG score: 0.11) and invasion (IG score: 0.1) compared to the other phenotypes with the CancerSEA database. BD also demonstrated therapeutic potential by interfering with the tumor cell–TME interactions by reducing the amyloid beta precursor protein and CD44 expression. Therefore, BD is a potential candidate to target the acidic TME induced metastatic process in BC.

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