scholarly journals A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yinglian Pan ◽  
Li Ping Jia ◽  
Yuzhu Liu ◽  
Yiyu Han ◽  
Qian Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Gynecologic Cancer ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Treatment ◽  
Prognostic Signature

Abstract Background In this study we aimed to identify a prognostic signature in BRCA1/2 mutations to predict disease progression and the efficiency of chemotherapy ovarian cancer (OV), the second most common cause of death from gynecologic cancer in women worldwide. Methods Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from data obtained from The Cancer Genome Atlas (TCGA) database. The area under the curve of the receiver operating characteristic curve was assessed, and the sensitivity and specificity of the prediction model were determined. Results A signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as the basis for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The three-year overall survival (OS) rates for the high- and low-risk group were approximately 38 and 100%, respectively. Chemotherapy treatment survival rates indicated that the high-risk group had significantly lower OS rates with adjuvant chemotherapy than the low-risk group. The one-, three-, and five-year OS were 100, 40, and 15% respectively in the high-risk group. The survival rate of the high-risk group declined rapidly after 2 years of OV chemotherapy treatment. Multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development. Conclusion In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with BRCA1/2 mutations, and can be used to predict prognosis and the efficiency of chemotherapy.

scholarly journals A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy

2020 ◽  
Author(s):  
Yinglian Pan ◽  
LiPing Jia ◽  
Yuzhu Liu ◽  
Yiyu Han ◽  
Qian Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Gynecologic Cancer ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Treatment ◽  
Prognostic Signature

Abstract Background: In this study we aimed to identify a prognostic signature in BRCA1/2 mutations to predict disease progression and the efficiency of chemotherapy ovarian cancer (OV), the second most common cause of death from gynecologic cancer in women worldwide. Methods: Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from data obtained from The Cancer Genome Atlas (TCGA) database. The area under the curve of the receiver operating characteristic curve was assessed, and the sensitivity and specificity of the prediction model were determined.Results: A signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as the basis for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The three-year overall survival (OS) rates for the high- and low-risk group were approximately 38% and 100%, respectively. Chemotherapy treatment survival rates indicated that the high-risk group had significantly lower OS rates with adjuvant chemotherapy than the low-risk group. The one-, three-, and five-year OS were 100%, 40%, and 15% respectively in the high-risk group. The survival rate of the high-risk group declined rapidly after two years of OV chemotherapy treatment. Multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development. Conclusion: In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with BRCA1/2 mutations, and can be used to predict prognosis and the efficiency of chemotherapy.

scholarly journals Identification of a Five-Autophagy-Related-lncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

2021 ◽  
Vol 7 ◽  
Author(s):  
Xiaoyu Deng ◽  
Qinghua Bi ◽  
Shihan Chen ◽  
Xianhua Chen ◽  
Shuhui Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Prediction Ability ◽  
Cox Regression Analysis

Although great progresses have been made in the diagnosis and treatment of hepatocellular carcinoma (HCC), its prognostic marker remains controversial. In this current study, weighted correlation network analysis and Cox regression analysis showed significant prognostic value of five autophagy-related long non-coding RNAs (AR-lncRNAs) (including TMCC1-AS1, PLBD1-AS1, MKLN1-AS, LINC01063, and CYTOR) for HCC patients from data in The Cancer Genome Atlas. By using them, we constructed a five-AR-lncRNA prognostic signature, which accurately distinguished the high- and low-risk groups of HCC patients. All of the five AR lncRNAs were highly expressed in the high-risk group of HCC patients. This five-AR-lncRNA prognostic signature showed good area under the curve (AUC) value (AUC = 0.751) for the overall survival (OS) prediction in either all HCC patients or HCC patients stratified according to several clinical traits. A prognostic nomogram with this five-AR-lncRNA signature predicted the 3- and 5-year OS outcomes of HCC patients intuitively and accurately (concordance index = 0.745). By parallel comparison, this five-AR-lncRNA signature has better prognosis accuracy than the other three recently published signatures. Furthermore, we discovered the prediction ability of the signature on therapeutic outcomes of HCC patients, including chemotherapy and immunotherapeutic responses. Gene set enrichment analysis and gene mutation analysis revealed that dysregulated cell cycle pathway, purine metabolism, and TP53 mutation may play an important role in determining the OS outcomes of HCC patients in the high-risk group. Collectively, our study suggests a new five-AR-lncRNA prognostic signature for HCC patients.

scholarly journals A Nine-Immune-Related Gene Prognostic Signature for Predicting Outcomes in High-Grade Serous Ovarian Cancer

2021 ◽  
Author(s):  
Yahui Jiang ◽  
Tianjiao Lyu ◽  
Tianyu Zhou ◽  
Yiwen Shi ◽  
Weiwei Feng
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Scores ◽  
High Grade ◽  
Lasso Regression ◽  
Prognostic Signature

Abstract Background: Recently, immune system has been shown to be indispensable for ovarian cancer progression. The key immune-related genes (IRGs) related to the overall survival of ovarian cancer patients should be taken seriously. Here, we screened 9 survival-related IRGs in high-grade serous ovarian cancer (HGSOC) and build a prognostic signature to predict the outcome of HGSOC patients.Methods: We downloaded RNA-sequence profiles from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to identify differentially expressed genes between normal fallopian tube and HGSOC. Among these genes, IRGs were filtered based on the Immunology Database and Analysis Portal (ImmPort). Using univariate Cox regression, Lasso regression and multivariate Cox regression, we selected 9 survival-related IRGs and established a prognostic signature to compute the risk score. Patients were divided into a low-risk group and a high-risk group, and the immunological feature differences between them were analysed with the ESTIMATE R package, TIMER and GSEA software. Moreover, the prognostic signature was validated by data from Gene Expression Omnibus (GEO) datasets.Results: We obtained 1544 differentially expressed genes in HGSOC compared with normal fallopian tube, among which 99 genes were related to immunology. After univariate Cox regression, Lasso regression and multivariate Cox regression, nine IRGs (HLA-F, PSMC1, PI3, CXCL10, CXCL9, CXCL11, LRP1, STAT1 and OGN) were identified as optimal survival-related IRGs and used to establish a prognostic signature for calculating the risk scores of HGSOC patients. The prognostic signature showed its efficiency in predicting the overall survival of HGSOC patients in TCGA training cohort (p=1.018e-8) and GEO test cohort (p=2.632e-2). Age and risk scores were independent risk factors for overall survival. As the risk scores increased, the proportions of neutrophil, dendritic cells, CD8+ T cells, CD4+ T cells and B cells decreased (p values were 0.026, 1.909e-4, 9.165e-10, 0.003 and 2.658e-4, respectively). In addition, 21 out of 24 HLA-related genes were highly expressed in the low-risk group than in the high-risk group. The above might prompt a stronger immune response in the low-risk group.Conclusions: Our study constructed a nine-IRG-based prognostic signature that could effectively predict the overall survival of HGSOC patients and become a promising therapeutic target for HGSOC treatments.

scholarly journals A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy

2020 ◽  
Author(s):  
Yinglian Pan ◽  
LiPing Jia ◽  
Yuzhu Liu ◽  
Yiyu Han ◽  
Qian Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Patient Choice ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Treatment

Abstract Background: Ovarian cancer (OV) is the most common type of primary female reproductive cancer. BRCA1/2 gene is an important biomarker for evaluating the risk of OV, breast cancer and other related tumors and influences patient choice of individualized treatment. A powerful signature to predict OV prognosis and improve treatment personalization is urgently needed. This study aimed to identify a novel OV-related lncRNA prognostic biomarker.Methods: A Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from The Cancer Genome Atlas (TCGA) database. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was assessed, and the sensitivity and specificity of the prediction model were determined.Results: The signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as a criterion for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The 3-year overall survival (OS) rates for the high- and low-risk groups were approximately 38% and 100%, respectively. Chemotherapy treatment survival rates indicated that high-risk groups had significantly shorter OS rates with adjuvant chemotherapy than the low-risk groups. The OS of 1-, 3- and 5- years were 100%, 40%, and 15% in the high-risk groups respectively. The survival rate of the high-risk group declined rapidly after two years of OA chemotherapy treatment. In addition, multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development.Conclusion: In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with in BRCA1/2 mutations to predict prognosis and chemotherapy efficiency.

scholarly journals Multi-Omics Profiling Identifies Risk Hypoxia-Related Signatures for Ovarian Cancer Prognosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingyu Chen ◽  
Hua Lan ◽  
Dong He ◽  
Runshi Xu ◽  
Yao Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Cancer Prognosis ◽  
High Risk Patients ◽  
Risk Patients

BackgroundOvarian cancer (OC) has the highest mortality rate among gynecologic malignancy. Hypoxia is a driver of the malignant progression in OC, which results in poor prognosis. We herein aimed to develop a validated model that was based on the hypoxia genes to systematically evaluate its prognosis in tumor immune microenvironment (TIM).ResultsWe identified 395 hypoxia-immune genes using weighted gene co-expression network analysis (WGCNA). We then established a nine hypoxia-related genes risk model using least absolute shrinkage and selection operator (LASSO) Cox regression, which efficiently distinguished high-risk patients from low-risk ones. We found that high-risk patients were significantly related to poor prognosis. The high-risk group showed unique immunosuppressive microenvironment, lower antigen presentation, and higher levels of inhibitory cytokines. There were also significant differences in somatic copy number alterations (SCNAs) and mutations between the high- and low-risk groups, indicating immune escape in the high-risk group. Tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms showed that low-risk patients are significantly responsive to programmed cell death protein-1 (PD-1) inhibitors.ConclusionsIn this study, we highlighted the clinical significance of hypoxia in OC and established a hypoxia-related model for predicting prognosis and providing potential immunotherapy strategies.

scholarly journals A Novel Signature Based on Pyroptosis-Related Genes for Predicting Breast Cancer

2021 ◽  
Author(s):  
Shuang Shen ◽  
Xin Chen ◽  
Rui Qu ◽  
Youming Guo ◽  
Yingying Su ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Independent Predictive Factor ◽  
Tumour Immunity

Abstract Background: Breast cancer (BC) surpassed lung cancer as the most frequent malignant tumour in women. In recent years, pyroptosis has revealed itself as an inflammatory form of programmed cell death. However, it is unclear as to the expression of genes associated with pyroptosis in BC and its relationship to prognosis. Results: In this study, we identified 31 pyroptosis regulators that are differentially expressed between BC and normal breast. The differently expressed genes (DEG) allow BC patients to be divided into three subtypes. Through single-factor and multi-factor COX regression and the application of least absolute contraction and selection operator (LASSO) Cox regression method, the survival prognostic value of each gene related to pyroptosis in The Cancer Genome Atlas (TCGA) cohort was evaluated, and a 4-gene signature was constructed. BC patients of the TCGA cohort are divided into low-risk or high-risk groups by risk score. The survival of the low-risk group was significantly higher than the high-risk group (P <0.001). Using the median risk score from the TCGA cohort, BC patients from the Gene Expression Omnibus (GEO) cohort were divided into two risk sub-groups and similar conclusions were drawn. In combination with clinicopathological characteristics, the risk score is an independent predictive factor of OS in BC patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) indicated that the high-risk group's immune genes were enriched and immune status was reduced. Conclusions: In conclusion, pyroptosis-related genes are important for tumour immunity and can be used to predict the prognosis of BC.

scholarly journals Identification of a novel autophagy signature for predicting survival in patients with lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11074
Author(s):  
Jin Duan ◽  
Youming Lei ◽  
Guoli Lv ◽  
Yinqiang Liu ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Cell Analysis ◽  
Prognostic Signature

Background Lung adenocarcinoma (LUAD) is the most commonhistological lung cancer subtype, with an overall five-year survivalrate of only 17%. In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature. Methods In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (n = 490) for a training and testing dataset, and GSE50081 (n = 127) as the external validation dataset.The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients. Results We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0.05 and |Fold change| > 1.5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low-risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels. Conclusion Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.

A Novel Ferroptosis-Related Lncrnas Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

2021 ◽  
Author(s):  
Meiling Jin ◽  
Diangeng Li
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Prognostic Signature

Abstract BackgroundPapillary renal cell carcinoma (PRCC) is a common renal cell carcinoma. Recent studies have reported that ferroptosis is involved in the occurrence and development of tumors. Long non-coding RNAs could be used as independent biomarkers for the diagnosis and prognosis of a variety of tumors, and many lncRNAs are related to the pathogenesis of PRCC. However, there are few studies on the ferroptosis-related lncRNAs of PRCC. This study aimed to establish ferroptosis-related lncRNAs prognostic signature in patients with PRCC.MethodsGene expression profile and clinical information of patients with PRCC were obtained from The Cancer Genome Atlas (TCGA) database. Lasso-Penalzed Cox regression and univariate Cox regression analysis were utilized for model construction. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Immune cell infiltration and immune function were compared between the high-risk and low-risk groups. Chemotherapy sensitivity analysis was also performed. ResultsWe constructed a prognostic signature consisted of 15 ferroptosis-related lncRNAs. The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the lncRNAs signature was 0.930, exhibiting robust prognostic capacity. The high-risk group had a greater degree of immune cell infiltration, such as B cells, T cell CD8, macrophages, NK cell, etc., compared with the low-risk group. There were significant differences in inflammation-promoting, parainflammation and Type I IFN reponse between the low-risk and high-risk groups. The expressions of immune checkpoints including CD80, IDO1, LAG3, etc. were significantly higher in high-risk group. Chemotherapy sensitivity analysis showed that MNX1-AS1, ZFAS1, MIR4435-2HG and ADAMTS9-AS1 were significantly correlated with the sensitivity of some chemotherapy drugs. ConclusionWe demonstrated that a ferroptosis-related lncRNAs prognostic signature could be a novel biomarker for PRCC. Our findings could provide a new insight for immune research and treatment strategies for patients with PRCC.

scholarly journals Ferroptosis regulator genes are a favorable biomarker for hepatocellular carcinoma

2021 ◽  
Author(s):  
Yongfei He ◽  
Shuqi Zhao ◽  
Zhongliu Wei ◽  
Xin Zhou ◽  
Tianyi Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Clinical Information ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regulator Genes ◽  
The Relationship

Abstract BackgroundIn this study, we comprehensively analyzed the relationship between ferroptosis regulator genes (FRGs) and prognosis of hepatocellular carcinoma (HCC), determined the prognostics value of FRGs, established a prediction model, and explored the relationship with immunotherapy for HCC.MethodsThe mRNA transcriptional levels and clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA) database. The 24 FRGs were combined with the differential expression genes (DEGs) of HCC for further analysis. The prognostics values of differential FRGs via the construction of model and validation by the Cox regression analysis.ResultThere were three genes (CARS1, FANCD2, and SLC7A11) were identified as independent risk factors for HCC, and a predictive model was constructed based on CARS1, FANCD2, and SLC7A11. The model showed that the low-risk group HCC patients with a more prolonged overall survival (OS) than the high-risk group (P=0.001). The high-risk group with higher expression of FRGs than the low-risk group. Finally, the relations between FGEs and immune infiltration showed that CARS1, FANCD2, and SLC7A11 had a positive relationship with macrophage infiltration. From these, three genes might be the potential therapeutic targets.ConclusionOur study indicated that CARS1, FANCD2, and SLC7A11 might have potential value for therapeutic strategies as practical and reliable prognostic tools for HCC.

scholarly journals A Potential Immune-Related Long Non-coding RNA Prognostic Signature for Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue Pan ◽  
Fangfang Bi
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Risk Group ◽  
Characteristic Curve ◽  
Gene Expression Omnibus ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Ovarian cancer (OC), the most lethal gynecologic malignancy, ranks fifth in cancer deaths among women, largely because of late diagnosis. Recent studies suggest that the expression levels of immune-related long non-coding RNAs (lncRNAs) play a significant role in the prognosis of OC; however, the potential of immune-related lncRNAs as prognostic factors in OC remains unexplored. In this study, we aimed to identify a potential immune-related lncRNA prognostic signature for OC patients. We used RNA sequencing and clinical data from The Cancer Genome Atlas and the Gene Expression Omnibus database to identify immune-related lncRNAs that could serve as useful biomarkers for OC diagnosis and prognosis. Univariate Cox regression analysis was used to identify the immune-related lncRNAs with prognostic value. Functional annotation of the data was performed through the GenCLiP310 website. Seven differentially expressed lncRNAs (AC007406.4, AC008750.1, AL022341.2, AL133351.1, FAM74A7, LINC02229, and HOXB-AS2) were found to be independent prognostic factors for OC patients. The Kaplan-Meier curve indicated that patients in the high-risk group had a poorer survival outcome than those in the low-risk group. The receiver operating characteristic curve revealed that the predictive potential of the immune-related lncRNA signature for OC was robust. The prognostic signature of the seven lncRNAs was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the signature of the seven lncRNAs was an independent prognostic factor for OC patients. Finally, we constructed a nomogram model and a competing endogenous RNA network related to the lncRNA prognostic signature. In conclusion, our study reveals novel immune-related lncRNAs that may serve as independent prognostic factors in OC.

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