scholarly journals A prognostic risk model constructed by proteins in predicting prognosis for ovarian cancer

Author(s):  
yan rong ◽  
Liangchen Niu ◽  
Li Li

Abstract BackgroundsOvarian cancer is the most lethal malignant tumor in gynecological cancers worldwide. Approximately 70% of patients have a poor prognosis, who experienced progression or recurrence within 5 years. The aim of this study attempts is to screen out the potential prognosis-related proteins and establish a prognostic risk model for predicting the prognostic risk for patients with ovarian cancer.MethodData were obtained from the Cancer Proteome Atlas (TCPA) and the Cancer Genome Atlas (TCGA). The proteins significantly related to survival risk in ovarian cancer patients were screened out by Kaplan-Meier test and COX regression analysis. A prognostic risk model was constructed based on the optimal proteins selected by multivariate Cox analysis. The prognostic risk model was validated in different clinical characteristics. The sankyl diagram was used to visualize the relationship between the prognosis-related proteins and their co-expression proteins.ResultsA prognostic risk model consisting of seven proteins that significantly related to prognosis was established. Patients with high risk score were associated with poor survival and relative protein expression. In the multivariate cox regress analysis, only age and the risk score were the independence prognosis factors. The AUC for the risk score was 0.721 in ROC curve for patients under 70 years old. Pearson’s correlation analysis showed that 25 co-expression proteins correlated with the prognosis-related proteins.ConclusionOur study demonstrated that a novel prognostic risk model constructed by proteins could predict prognosis for patients with ovarian cancer.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Didi Zuo ◽  
Chao Li ◽  
Tao Liu ◽  
Meng Yue ◽  
Jiantao Zhang ◽  
...  

AbstractMetabolic genes have played a significant role in tumor development and prognosis. In this study, we constructed a metabolic risk model to predict the prognosis of colon cancer based on The Cancer Genome Atlas (TCGA) and validated the model by Gene Expression Omnibus (GEO). We extracted 753 metabolic genes and identified 139 differentially expressed genes (DEGs) from TCGA database. Then we conducted univariate cox regression analysis and Least Absolute Shrinkage and Selection Operator Cox regression analysis to identify prognosis-related genes and construct the metabolic risk model. An eleven-gene prognostic model was constructed after 1000 resamples. The gene signature has been proved to have an excellent ability to predict prognosis by Kaplan–Meier analysis, time-dependent receiver operating characteristic, risk score, univariate and multivariate cox regression analysis based on TCGA. Then we validated the model by Kaplan–Meier analysis and risk score based on GEO database. Finally, we performed a weighted gene co-expression network analysis and protein–protein interaction network on DEGs, and Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology enrichment analyses were conducted. The results of functional analyses showed that most significantly enriched pathways focused on metabolism, especially glucose and lipid metabolism pathways.


2021 ◽  
Author(s):  
Liu-qing Zhou ◽  
Jie-yu Zhou ◽  
Yao Hu

Abstract Background: N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. m6A modifications are known to modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood.Methods: Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a risk prognostic model, and consensus clustering analysis, we analyzed the 12 m6A-related lncRNAs in HNSCC samples data using the data from The Cancer Genome Atlas (TCGA) database.Results: We found twelve m6A-related lncRNAs in the training cohort and validated in all cohorts by Kaplan-Meier and Cox regression analyses, and revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC prognosis. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs.Conclusions: In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC prognosis and provide potential prediction outcome and new therapeutic target for HNSCC patients.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Liu-qing Zhou ◽  
Jin-xiong Shen ◽  
Jie-yu Zhou ◽  
Yao Hu ◽  
Hong-jun Xiao

AbstractN6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan–Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Yu Zhang ◽  
Qingjian Ye ◽  
Junxian He ◽  
Peigen Chen ◽  
Jing Wan ◽  
...  

Ovarian cancer (OvCa) is an intractable gynecological malignancy due to the high recurrence rate. Several molecular biomarkers have been previously screened for early identifying patients with a high recurrence risk and poor prognosis. However, all the known studies focused on a single type of RNAs, not integrating various types. This study was to construct a new multi-RNA-based model to predict the recurrence and prognosis for OvCa patients by using the messenger RNA (mRNA, including long noncoding RNA (lncRNA)) and microRNA (miRNA) sequencing data of The Cancer Genome Atlas database. After univariate Cox regression and least absolute shrinkage and selection operator analyses, a multi-RNA-based signature (2 miRNAs: hsa-miR-508, hsa-miR-506; 1 lncRNA: TM4SF1-AS1; 11 mRNAs: MAGI3, SLAMF7, GLI2, PDK1, ARID3A, PLEKHG4B, TNFAIP8L3, C1QTNF3, NDUFAF1, CH25H, TMEM129) was generated and used to establish a risk score model. The high- and low-risk patients classified by the median risk score exhibited significantly different recurrence risks (89% versus 61%, p<0.001) and survival time (the area under the receiver operating characteristic curve (AUC) = 0.901 for 5-year disease-free survival (DFS)). This risk model was independent of other clinical features and superior to pathologic staging for DFS prediction (AUC, 0.906 versus 0.524; C-index, 0.633 versus 0.510). Furthermore, some new interaction axes were revealed to explain the possible functions of these RNAs (competing endogenous RNA: TM4SF1-AS1-miR-186-STEAP2, LINC00536-miR-508-STEAP2, LINC00475-miR-506-TMEM129; coexpression: LINC00598-PLEKHG4B). In conclusion, this multi-RNA-based risk model may be clinically useful to stratify OvCa patients with different recurrence risks and survival outcomes and included RNAs may be potential therapeutic targets.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhengxin Wu ◽  
Jinshui Tan ◽  
Yifan Zhuang ◽  
Mengya Zhong ◽  
Yubo Xiong ◽  
...  

Abstract Background Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. Methods Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan–Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. Results Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan–Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. Conclusion In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.


2021 ◽  
Author(s):  
Gen-hua Yang

Abstract Background and AimStudies have recently shown that immune-related lncRNAs play a vital role in the occurrence and development of human malignancies. However, the study in gastric cancer (GC) remains unclear. Here, we aimed to identify immune-related lncRNAs and construct a risk score model to predict the prognosis of GC patients.Methods:RNA expression data and clinical characteristics of GC were download from The Cancer Genome Atlas (TCGA) database. Immune genes were obtained from the Molecular Signatures Database (MSigDB). Immune-related lncRNAs were acquired by correlation coefficient between the immune genes and lncRNAs using “limma R” package and Cytoscape 3.6.1. The risk score model was constructed by univariate and multivariate Cox regression, and its prognostic value was verified in TCGA cohort. Results:A total of 146 immune-related lncRNAs were obtained compared 375 GC samples with 32 normal samples. A five immune-related lncRNA (AP001528.2, LINC02542, LINC02526, PVT1 and LINC01094) risk score model was constructed to predict prognosis of GC patients by Cox regression analysis. Moreover, GC patients with higher risk score had a poorer overall survival than that with lower risk score (P<0.001). Furthermore, ROC analysis revealed that the risk score model had the best predictive effect compared with clinicopathological features during 5 years followed-up (AUC = 0.679). Indeed, PCA analysis showed that the patients in the low- and high- group were significantly distinguished in different directions based on the risk score model. Conclusion:This study indicated that a five immune-related lncRNA risk score model possessed a satisfactory predictive prognosis, which might be potential prognostic biomarkers and immunotherapy targets for GC patients in future.


2021 ◽  
Author(s):  
Yanan Shan ◽  
Ran He ◽  
Xiaowei Yang ◽  
Siwen Zang ◽  
Shan Yao ◽  
...  

Abstract Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long noncoding RNA (lncRNA) in thyroid cancer and explored its prognostic value. A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb), respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1166 autophagy-associated lncRNAs. Subsequently we conducted univariate Cox regression analysis and multivariate Cox regression analysis, a nine-autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471, AL162231.2) significantly associated with prognosis was identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer. In this study, a nine autophagy-related lncRNAs in thyroid cancer were established to predict the prognosis of thyroid cancer patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jianwei Lin ◽  
Zichao Cao ◽  
Dingye Yu ◽  
Wei Cai

The prognosis of colon adenocarcinoma (COAD) remains poor. However, the specific and sensitive biomarkers for diagnosis and prognosis of COAD are absent. Transcription factors (TFs) are involved in many biological processes in cells. As the molecule of the signal pathway of the terminal effectors, TFs play important roles in tumorigenesis and development. A growing body of research suggests that aberrant TFs contribute to the development of COAD, as well as to its clinicopathological features and prognosis. In consequence, a few studies have investigated the relationship between the TF-related risk model and the prognosis of COAD. Therefore, in this article, we hope to develop a prognostic risk model based on TFs to predict the prognosis of patients with COAD. The mRNA transcription data and corresponding clinical data were downloaded from TCGA and GEO. Then, 141 differentially expressed genes, validated by the GEPIA2 database, were identified by differential expression analysis between normal and tumor samples. Univariate, multivariate and Lasso Cox regression analysis were performed to identify seven prognostic genes (E2F3, ETS2, HLF, HSF4, KLF4, MEIS2, and TCF7L1). The Kaplan–Meier curve and the receiver operating characteristic curve (ROC, 1-year AUC: 0.723, 3-year AUC: 0.775, 5-year AUC: 0.786) showed that our model could be used to predict the prognosis of patients with COAD. Multivariate Cox analysis also reported that the risk model is an independent prognostic factor of COAD. The external cohort (GSE17536 and GSE39582) was used to validate our risk model, which indicated that our risk model may be a reliable predictive model for COAD patients. Finally, based on the model and the clinicopathological factors, we constructed a nomogram with a C-index of 0.802. In conclusion, we emphasize the clinical significance of TFs in COAD and construct a prognostic model of TFs, which could provide a novel and reliable model for the prognosis of COAD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Bixian Luo ◽  
Jianwei Lin ◽  
Wei Cai ◽  
Mingliang Wang

The prognosis of advanced colon adenocarcinoma (COAD) remains poor. However, existing methods are still difficult to assess patient prognosis. Pyroptosis, a lytic and inflammatory process of programmed cell death caused by the gasdermin protein, is involved in the development and progression of various tumors. Moreover, there are no related studies using pyroptosis-related genes to construct a model to predict the prognosis of COAD patients. Thus, in this study, bioinformatics methods were used to analyze the data of COAD patients downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a risk model for the patient prognosis. TCGA database was used as the training set, and GSE39582 downloaded from GEO was used as the validation set. A total of 24 pyroptosis-related genes shown significantly different expression between normal and tumor tissues in COAD and seven genes (CASP4, CASP5, CASP9, IL6, NOD1, PJVK, and PRKACA) screened by univariate and LASSO cox regression analysis were used to construct the risk model. The receiver operating characteristic (ROC) and Kaplan–Meier (K–M curves) curves showed that the model based on pyroptosis-related genes can be used to predict the prognosis of COAD and can be validated by the external cohort well. Then, the clinicopathological factors were combined with the risk score to establish a nomogram with a C-index of 0.774. In addition, tissue validation results also showed that CASP4, CASP5, PRKACA, and NOD1 were differentially expressed between tumor and normal tissues from COAD patients. In conclusion, the risk model based on the pyroptosis-related gene can be used to assess the prognosis of COAD patients well, and the related genes may become the potential targets for treatment.


2021 ◽  
Author(s):  
Zhengxin Wu ◽  
Jinshui Tan ◽  
Yifan Zhuang ◽  
Mengya Zhong ◽  
Yubo Xiong ◽  
...  

Abstract Background Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. Methods Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. Results Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan-Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. Conclusion In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.


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