scholarly journals A highly expressed mRNA signature for predicting survival in patients with stage I/II non-small-cell lung cancer after operation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nan Ma ◽  
Lu Si ◽  
Meiling Yang ◽  
Meihua Li ◽  
Zhiyi He
Keyword(s):  
High Risk ◽  
Roc Curve ◽  
Expression Profiles ◽  
Low Risk ◽  
Stage I ◽  
Risk Scores ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Nsclc Patients ◽  
Rna Signature

AbstractThere is an urgent need to identify novel biomarkers that predict the prognosis of patients with NSCLC. In this study,we aim to find out mRNA signature closely related to the prognosis of NSCLC by new algorithm of bioinformatics. Identification of highly expressed mRNA in stage I/II patients with NSCLC was performed with the “Limma” package of R software. Survival analysis of patients with different mRNA expression levels was subsequently calculated by Cox regression analysis, and a multi-RNA signature was obtained by using the training set. Kaplan–Meier estimator, log-rank test and receiver operating characteristic (ROC) curves were used to analyse the predictive ability of the multi-RNA signature. RT-PCR used to verify the expression of the multi-RNA signature, and Westernblot used to verify the expression of proteins related to the multi-RNA signature. We identified fifteen survival-related mRNAs in the training set and classified the patients as high risk or low risk. NSCLC patients with low risk scores had longer disease-free survival than patients with high risk scores. The fifteen-mRNA signature was an independent prognostic factor, as shown by the ROC curve. ROC curve also showed that the combined model of the fifteen-mRNA signature and tumour stage had higher precision than stage alone. The expression of fifteen mRNAs and related proteins were higher in stage II NSCLC than in stage I NSCLC. Multi-gene expression profiles provide a moderate prognostic tool for NSCLC patients with stage I/II disease.

scholarly journals An autophagy-related long non-coding RNA signature for patients with colorectal cancer

2021 ◽  
Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.

scholarly journals Risk Score Generated from CT-Based Radiomics Signatures for Overall Survival Prediction in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3616
Author(s):  
Viet-Huan Le ◽  
Quang-Hien Kha ◽  
Truong Nguyen Khanh Hung ◽  
Nguyen Quoc Khanh Le
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Low Risk ◽  
Survival Prediction ◽  
Clinical Parameters ◽  
Training Set ◽  
Prediction Ability ◽  
Nsclc Patients ◽  
Overall Survival Prediction

This study aimed to create a risk score generated from CT-based radiomics signatures that could be used to predict overall survival in patients with non-small cell lung cancer (NSCLC). We retrospectively enrolled three sets of NSCLC patients (including 336, 84, and 157 patients for training, testing, and validation set, respectively). A total of 851 radiomics features for each patient from CT images were extracted for further analyses. The most important features (strongly linked with overall survival) were chosen by pairwise correlation analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and univariate Cox proportional hazard regression. Multivariate Cox proportional hazard model survival analysis was used to create risk scores for each patient, and Kaplan–Meier was used to separate patients into two groups: high-risk and low-risk, respectively. ROC curve assessed the prediction ability of the risk score model for overall survival compared to clinical parameters. The risk score, which developed from ten radiomics signatures model, was found to be independent of age, gender, and stage for predicting overall survival in NSCLC patients (HR, 2.99; 95% CI, 2.27–3.93; p < 0.001) and overall survival prediction ability was 0.696 (95% CI, 0.635–0.758), 0.705 (95% CI, 0.649–0.762), 0.657 (95% CI, 0.589–0.726) (AUC) for 1, 3, and 5 years, respectively, in the training set. The risk score is more likely to have a better accuracy in predicting survival at 1, 3, and 5 years than clinical parameters, such as age 0.57 (95% CI, 0.499–0.64), 0.552 (95% CI, 0.489–0.616), 0.621 (95% CI, 0.544–0.689) (AUC); gender 0.554, 0.546, 0.566 (AUC); stage 0.527, 0.501, 0.459 (AUC), respectively, in 1, 3 and 5 years in the training set. In the training set, the Kaplan–Meier curve revealed that NSCLC patients in the high-risk group had a lower overall survival time than the low-risk group (p < 0.001). We also had similar results that were statistically significant in the testing and validation set. In conclusion, risk scores developed from ten radiomics signatures models have great potential to predict overall survival in NSCLC patients compared to the clinical parameters. This model was able to stratify NSCLC patients into high-risk and low-risk groups regarding the overall survival prediction.

scholarly journals Identification of Metastasis-Related Signature For Predicting Survival In Osteosarcoma

2021 ◽  
Author(s):  
Song Shi ◽  
Shuaijie Yang ◽  
Zhenyu Zhou ◽  
Kai Sun ◽  
Ran Tao ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Gene Signature ◽  
Low Risk ◽  
Risk Scores ◽  
Activation Markers

Abstract BackgroundRNA sequencing has become a powerful tool for exploring tumor recurrence or metastasis mechanisms. In this study, we aimed to develop a signature to improve the prognostic predictions of osteosarcoma.Materials and methodsBy comparing the expression profiles between metastatic and non-metastatic samples, we obtained 57 metastatic-related gene signatures. Then we constructed a 3‐gene signature to predict the prognostic risk of osteosarcoma patients by the Cox proportional hazards regression model. The risk score derived from this signature could successfully stratify osteosarcoma patients into subgroups with different survival outcomes.ResultsPatients in the low-risk group showed more prolonged overall survival than those in the high-risk group. And the performance was validated with another independent dataset. Multivariate cox regression revealed that the risk score served as an independent risk factor. Besides, we found that patients with low-risk scores had higher expression levels of immune-related signatures, suggesting an active immune status in those patients. Using the CIBERSORT database, we further systematically analyzed the relationships between the risk score and immune cell infiltration levels, as well as the immune activation markers. Higher infiltration of immune cells (CD8 T cells, monocytes, M2 macrophages, and memory B cells) and higher levels of immune cytotoxic markers (GZMA, GMZB, IFNG, and TNF) were observed in patients in the low-risk group.ConclusionsIn summary, this 3-gene signature could be a reliable marker for prognostic evaluation and help clinicians identify high‐risk patients.

scholarly journals A prognostic model based on immune-related long noncoding RNAs for patients with epithelial ovarian cancer

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Yao Peng ◽  
Hui Wang ◽  
Qi Huang ◽  
Jingjing Wu ◽  
Mingjun Zhang
Keyword(s):  
High Risk ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Principal Component ◽  
Risk Groups ◽  
Low Risk ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Validation Set

Abstract Background Long noncoding RNAs (lncRNAs) are important regulators of gene expression and can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNAs play an important role in the tumour immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumour patients. Epithelial ovarian cancer (EOC) is characterized by a high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on immune-related lncRNAs associated with survival in EOC. Methods We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database and identified differentially expressed genes through differential expression analysis. Immune-related lncRNAs were obtained through intersection and coexpression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into a training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were performed to construct an immune-related lncRNA signature. Kaplan–Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were performed for verification in the training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GSEA) and the Timer data portal. Results An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature was used to divide patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group and was verified to be robust in both the validation set and the combination set. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.). Conclusions We identified and established a prognostic signature of immune-related lncRNAs in EOC, which will be of great value in predicting the prognosis of clinical patients and may provide a new perspective for immunological research and individualized treatment in EOC.

scholarly journals More Evidences for Prediction Model of Radiosensitivity

2021 ◽  
Author(s):  
Zixuan Du ◽  
Xinyan Zhang ◽  
Zaixiang Tang
Keyword(s):  
High Risk ◽  
Prediction Model ◽  
Risk Score ◽  
Cox Regression ◽  
Image Data ◽  
Low Risk ◽  
Risk Scores ◽  
Cox Regression Analysis ◽  
Radiotherapy Group ◽  
Definition Of

With the development of precision medicine, searching for potential biomarkers plays a major role in personalized medicine. Therefore, how to predict radiosensitivity to improve radiotherapy is a burning question. The definition of radiosensitivity is complex. Radiosensitive gene/biomarker can be useful for predicting which patients would benefit from radiotherapy. The discovery of radiosensitivity biomarkers require multiple pieces of evidence. A prediction model of breast cancer radiosensitivity based on 6 genes was established. We had put forward some supplements on the basis of this study. We found that there were no differences between high-risk scores and low-risk scores in the non-radiotherapy group. Patients who receiving radiotherapy had a significantly better overall survival than non-radiotherapy patients in the predicted low-risk score patients. Furthermore, there was no difference between radiotherapy group and non-radiotherapy group in the high-risk score group. Those results firmly supported the prediction model of radiosensitivity. In addition, building a radiosensitivity prediction model was systematically discussed. Genes of model could be screened by different methods, such as Cox regression analysis, LASSO Cox regression method, random forest algorithm and other methods. In the future, precision radiotherapy might depend on the combination of multi-omics data and high dimensional image data.

scholarly journals Identification of the Prognostic Signature Associated With Tumor Immune Microenvironment of Uterine Corpus Endometrial Carcinoma Based on Ferroptosis-Related Genes

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinhui Liu ◽  
Yichun Wang ◽  
Huangyang Meng ◽  
Yin Yin ◽  
Hongjun Zhu ◽  
...  
Keyword(s):  
High Risk ◽  
Endometrial Carcinoma ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Expression Profiles ◽  
Risk Groups ◽  
Low Risk ◽  
Immune Microenvironment ◽  
Cox Regression Analysis ◽  
Uterine Corpus

Background: Uterine corpus endometrial carcinoma (UCEC) is the sixth most common cancer worldwide. Ferroptosis plays an important role in malignant tumors. However, the study of ferroptosis in the endometrial carcinoma remains blank.Methods: First, we constructed a ferroptosis-related signature based on the expression profiles from The Cancer Genome Atlas database. Then, patients were divided into the high-risk and low-risk groups based on this signature. The signature was evaluated by Kaplan–Meier analysis and receiver operating characteristic (ROC) analysis. We further investigated the relationship between this signature and immune microenvironment via CIBERSORT algorithm, ImmuCellAI, MAF, MSI sensor algorithm, GSEA, and GDSC.Results: This signature could be an independent prognostic factor based on multivariate Cox regression analysis. GSEA revealed that this signature was associated with immune-related phenotype. In addition, we indicated the different status of immune infiltration and response to the immune checkpoint between low-risk and high-risk groups. Patients in the low-risk group were more likely to present with a higher expression of immune checkpoint molecules and tumor mutation burden. Meanwhile, the low-risk patients showed sensitive responses to chemotherapy drugs.Conclusion: In summary, the six ferroptosis-related genes signature could be used in molecular subgrouping and accurately predict the prognosis of UCEC.

scholarly journals A Prognostic Model Based on Immune-Related Long Non-Coding RNAs for Patients With Epithelial Ovarian Cancer

2021 ◽  
Author(s):  
Yao Peng ◽  
Hui Wang ◽  
Qi Huang ◽  
Jingjing Wu ◽  
Mingjun Zhang
Keyword(s):  
High Risk ◽  
Immune Cell ◽  
Cox Regression ◽  
Principal Component ◽  
Risk Groups ◽  
Low Risk ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Validation Set ◽  
Differential Genes

Abstract Background: Long non-coding RNA (lncRNA), as an important regulator of gene expression, can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNA play an important role in the tumor immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumor patients. Epithelial ovarian cancer (EOC) is characterized by high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on the immune-related lncRNAs associated with survival in EOC. Methods: We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database, and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database, and identified differential genes through differential Expression analysis. Immune-related lncRNAs were obtained through taking intersection and co-expression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were used to construct an immune-related lncRNA signature. Kaplan-Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were applied to verification in the training set, training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GESA) and the Timer data portal.Results: An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature divided patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group, and was verified to be robust in both the training set and the combination set. This signature was identified as an independent prognostic biomarker. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.). Conclusions: we identified and established a prognostic signature of immune-related lncRNA in EOC, which is of great value in predicting the prognosis of clinical patients and may provide a new perspective for the immunological research and individualized treatment in EOC.

scholarly journals Assessing the clinical utility of genetic risk scores for targeted cancer screening

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Carly A. Conran ◽  
Zhuqing Shi ◽  
William Kyle Resurreccion ◽  
Rong Na ◽  
Brian T. Helfand ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Care ◽  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Clinical Utility ◽  
Low Risk ◽  
Risk Scores ◽  
Average Risk ◽  
Genetic Risk Scores

Abstract Background Genome-wide association studies have identified thousands of disease-associated single nucleotide polymorphisms (SNPs). A subset of these SNPs may be additively combined to generate genetic risk scores (GRSs) that confer risk for a specific disease. Although the clinical validity of GRSs to predict risk of specific diseases has been well established, there is still a great need to determine their clinical utility by applying GRSs in primary care for cancer risk assessment and targeted intervention. Methods This clinical study involved 281 primary care patients without a personal history of breast, prostate or colorectal cancer who were 40–70 years old. DNA was obtained from a pre-existing biobank at NorthShore University HealthSystem. GRSs for colorectal cancer and breast or prostate cancer were calculated and shared with participants through their primary care provider. Additional data was gathered using questionnaires as well as electronic medical record information. A t-test or Chi-square test was applied for comparison of demographic and key clinical variables among different groups. Results The median age of the 281 participants was 58 years and the majority were female (66.6%). One hundred one (36.9%) participants received 2 low risk scores, 99 (35.2%) received 1 low risk and 1 average risk score, 37 (13.2%) received 1 low risk and 1 high risk score, 23 (8.2%) received 2 average risk scores, 21 (7.5%) received 1 average risk and 1 high risk score, and no one received 2 high risk scores. Before receiving GRSs, younger patients and women reported significantly more worry about risk of developing cancer. After receiving GRSs, those who received at least one high GRS reported significantly more worry about developing cancer. There were no significant differences found between gender, age, or GRS with regards to participants’ reported optimism about their future health neither before nor after receiving GRS results. Conclusions Genetic risk scores that quantify an individual’s risk of developing breast, prostate and colorectal cancers as compared with a race-defined population average risk have potential clinical utility as a tool for risk stratification and to guide cancer screening in a primary care setting.

scholarly journals Identifying individuals with high risk of Alzheimer’s disease using polygenic risk scores

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ganna Leonenko ◽  
Emily Baker ◽  
Joshua Stevenson-Hoare ◽  
Annerieke Sierksma ◽  
Mark Fiers ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Prediction Accuracy ◽  
Genetic Risk Score ◽  
Low Risk ◽  
Risk Scores ◽  
Sample Mean ◽  
Polygenic Risk ◽  
Reliable Identification

AbstractPolygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optimal p-value threshold (pT) for SNP selection is and how to compare scores between studies and methods. We show that the best prediction accuracy is achieved with a model with two predictors (APOE and PRS excluding APOE region) with pT<0.1 for SNP selection. Prediction accuracy in a sample across different PRS approaches is similar, but individuals’ scores and their associated ranking differ. We show that standardising PRS against the population mean, as opposed to the sample mean, makes the individuals’ scores comparable between studies. Our work highlights the best strategies for polygenic profiling when assessing individuals for AD risk.

scholarly journals Development of prognosis model for colon cancer based on autophagy-related genes

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang
Keyword(s):  
Colon Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Patient Survival ◽  
Expression Profiles ◽  
Cox Regression Analysis ◽  
Risk Patients

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.

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