scholarly journals Establishment of a Gene Signature to Predict Prognosis for Patients with Lung Adenocarcinoma

2020 ◽  
Vol 21 (22) ◽  
pp. 8479
Author(s):  
Zhaodong Li ◽  
Fangyuan Qi ◽  
Fan Li

Accumulating evidence indicates that the reliable gene signature may serve as an independent prognosis factor for lung adenocarcinoma (LUAD) diagnosis. Here, we sought to identify a risk score signature for survival prediction of LUAD patients. In the Gene Expression Omnibus (GEO) database, GSE18842, GSE75037, GSE101929, and GSE19188 mRNA expression profiles were downloaded to screen differentially expressed genes (DEGs), which were used to establish a protein-protein interaction network and perform clustering module analysis. Univariate and multivariate proportional hazards regression analyses were applied to develop and validate the gene signature based on the TCGA dataset. The signature genes were then verified on GEPIA, Oncomine, and HPA platforms. Expression levels of corresponding genes were also measured by qRT-PCR and Western blotting in HBE, A549, and PC-9 cell lines. The prognostic signature based on eight genes (TTK, HMMR, ASPM, CDCA8, KIF2C, CCNA2, CCNB2, and MKI67) was established, which was independent of other clinical factors. The risk model offered better discrimination between risk groups, and patients with high-risk scores tended to have poor survival rate at 1-, 3- and 5-year follow-up. The model also presented better survival prediction in cancer-specific cohorts of age, gender, clinical stage III/IV, primary tumor 1/2, and lymph node metastasis 1/2. The signature genes, moreover, were highly expressed in A549 and PC-9 cells. In conclusion, the risk score signature could be used for prognostic estimation and as an independent risk factor for survival prediction in patients with LUAD.

2020 ◽  
Author(s):  
Dai Zhang ◽  
Si Yang ◽  
Yiche Li ◽  
Meng Wang ◽  
Jia Yao ◽  
...  

Abstract Background: Ovarian cancer (OV) is deemed as the most lethal gynecological cancer in women. The aim of this study was construct an effective gene prognostic model for OV patients.Methods: The expression profiles of glycolysis-related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed in training and test sets.Results: Based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4), a gene risk signature was identified to predict the outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high-grade OV, in the TCGA dataset, with areas under the curve of 0.709, 0.762, and 0.808 for 3-, 5- and 10-year survival, respectively. Similar results were found in the test sets, and the signature was also an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was constructed.Conclusion: Our study established a nine-GRG risk model and a nomogram to better perform on OV patients’ survival prediction. The risk model represents a promising and independent prognostic predictor for OV patients. Moreover, our study of GRGs could offer guidances for underlying mechanisms explorations in the future.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiahang Song ◽  
Yanhu Liu ◽  
Xiang Guan ◽  
Xun Zhang ◽  
Wenda Yu ◽  
...  

Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer (ESCA) type, which is also associated with the greatest malignant grade and low survival rates worldwide. Ferroptosis is recently discovered as a kind of programmed cell death, which is indicated in various reports to be involved in the regulation of tumor biological behaviors. This work focused on the comprehensive evaluation of the association between ferroptosis-related gene (FRG) expression profiles and prognosis in ESCC patients based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419 were selected to develop a novel ferroptosis-related gene signature for GEO and TCGA cohorts. The prognostic risk model exactly classified patients who had diverse survival outcomes. In addition, this study identified the ferroptosis-related signature as a factor to independently predict the risk of ESCC. Thereafter, we also constructed the prognosis nomogram by incorporating clinical factors and risk score, and the calibration plots illustrated good prognostic performance. Moreover, the association of the risk score with immune checkpoints was observed. Collectively, the proposed ferroptosis-related gene signature in our study is effective and has a potential clinical application to predict the prognosis of ESCC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Huadi Shi ◽  
Fulan Zhong ◽  
Xiaoqiong Yi ◽  
Zhenyi Shi ◽  
Feiyan Ou ◽  
...  

Background: Autophagy plays an important role in the development of cancer. However, the prognostic value of autophagy-related genes (ARGs) in cervical cancer (CC) is unclear. The purpose of this study is to construct a survival model for predicting the prognosis of CC patients based on ARG signature.Methods: ARGs were obtained from the Human Autophagy Database and Molecular Signatures Database. The expression profiles of ARGs and clinical data were downloaded from the TCGA database. Differential expression analysis of CC tissues and normal tissues was performed using R software to screen out ARGs with an aberrant expression. Univariate Cox, Lasso, and multivariate Cox regression analyses were used to construct a prognostic model which was validated by using the test set and the entire set. We also performed an independent prognostic analysis of risk score and some clinicopathological factors of CC. Finally, a clinical practical nomogram was established to predict individual survival probability.Results: Compared with normal tissues, there were 63 ARGs with an aberrant expression in CC tissues. A risk model based on 3 ARGs was finally obtained by Lasso and Cox regression analysis. Patients with high risk had significantly shorter overall survival (OS) than low-risk patients in both train set and validation set. The ROC curve validated its good performance in survival prediction, suggesting that this model has a certain extent sensitivity and specificity. Multivariate Cox analysis showed that the risk score was an independent prognostic factor. Finally, we mapped a nomogram to predict 1-, 3-, and 5-year survival for CC patients. The calibration curves indicated that the model was reliable.Conclusion: A risk prediction model based on CHMP4C, FOXO1, and RRAGB was successfully constructed, which could effectively predict the prognosis of CC patients. This model can provide a reference for CC patients to make precise treatment strategy.


2020 ◽  
Author(s):  
Dai Zhang ◽  
Si Yang ◽  
Yiche Li ◽  
Meng Wang ◽  
Jia Yao ◽  
...  

Abstract Background: Ovarian cancer (OV) is deemed as the most lethal gynecological cancer in women. The aim of this study was construct an effective gene prognostic model for OV patients.Methods: The expression profiles of glycolysis-related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed in training and test sets.Results: Based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4), a gene risk signature was identified to predict the outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high-grade OV, in the TCGA dataset, with areas under the curve of 0.709, 0.762, and 0.808 for 3-, 5- and 10-year survival, respectively. Similar results were found in the test sets, and the signature was also an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was constructed.Conclusion: Our study established a nine-GRG risk model and a nomogram to better perform on OV patients’ survival prediction. The risk model represents a promising and independent prognostic predictor for OV patients. Moreover, our study of GRGs could offer guidance for underlying mechanisms explorations in the future.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yugang Guo ◽  
Zhongyu Qu ◽  
Dandan Li ◽  
Fanghui Bai ◽  
Juan Xing ◽  
...  

AbstractFerroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P < 0.001). Receiver operating characteristic (ROC) curves and a principal component analysis further supported the accuracy of the model. Next, a prognostic nomogram combining FerRLSig with clinical features was established and showed favorable predictive efficacy for survival risk stratification. In addition, gene set enrichment analysis (GSEA) revealed that FerRLSig is involved in many malignancy-associated immunoregulatory pathways. Based on the risk model, we found that the immune status and response to immunotherapy, chemotherapy, and targeted therapy differed significantly between the high-risk and low-risk groups. These results offer novel insights into the pathogenesis of LUAD, including the contribution of ferroptosis-related lncRNAs, and reveal a prognostic indicator with the potential to inform immunological research and treatment.


2021 ◽  
Author(s):  
Dai Zhang ◽  
Si Yang ◽  
Yiche Li ◽  
Meng Wang ◽  
Jia yao ◽  
...  

Abstract Background: Ovarian cancer (OV) is deemed as the most lethal gynecological cancer in women. The aim of this study was construct an effective gene prognostic model for OV patients.Methods: The expression profiles of glycolysis-related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed in training and test sets.Results: Based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4), a gene risk signature was identified to predict the outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high-grade OV, in the TCGA dataset, with areas under the curve of 0.709, 0.762, and 0.808 for 3-, 5- and 10-year survival, respectively. Similar results were found in the test sets, and the signature was also an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was constructed.Conclusion: Our study established a nine-GRG risk model and a nomogram to better perform on OV patients’ survival prediction. The risk model represents a promising and independent prognostic predictor for OV patients. Moreover, our study of GRGs could offer guidance for underlying mechanisms explorations in the future.


2021 ◽  
Author(s):  
Song Shi ◽  
Shuaijie Yang ◽  
Zhenyu Zhou ◽  
Kai Sun ◽  
Ran Tao ◽  
...  

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.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hongjun Fei ◽  
Songchang Chen ◽  
Chenming Xu

Abstract Background Existing clinical methods for prognosis evaluating for Epithelial Ovarian Cancer (EOC) patients had defects of invasive, unsystematic and subjective and little data are available for individualizing treatment, therefore, to identify potential prognostic markers and new therapeutic targets for EOC is urgently required. Results Expression of 232 autophagy-related genes (ARGs) in 354 EOC and 56 human ovarian surface epithelial specimens from 7 independent laboratories were analyzed, 31 mRNAs were identified as DEARGs. We did functional and pathway enrichment analysis and constructed protein–protein interaction network for all DEARGs. To screen out candidate DEARGs related to EOC patients’ survival and construct an autophagy-related prognostic risk signature, univariate and multivariate Cox proportional hazards models were established separately. Finally, 5 optimal independent prognostic DEARGs (PEX3, DNAJB9, RB1, HSP90AB1 and CXCR4) were confirmed and the autophagy-related risk model was established by the 5 prognostic DEARGs. The accuracy and robustness of the prognostic risk model for survival prediction were evaluated and verified by analyzing the correlation between EOC patients’ survival status, clinicopathological features and risk scores. Conclusions The autophagy-related prognostic risk model can be independently used to predict overall survival in EOC patients, it can also potentially assist in individualizing treatment and biomarker development.


Author(s):  
Yongmei Wang ◽  
Guimin Zhang ◽  
Ruixian Wang

Background: This study aims to explore the prognostic values of CT83 and CT83-related genes in lung adenocarcinoma (LUAD). Methods: We downloaded the mRNA profiles of 513 LUAD patients (RNA sequencing data) and 246 NSCLC patients (Affymetrix Human Genome U133 Plus 2.0 Array) from TCGA and GEO databases. According to the median expression of CT83, the TCGA samples were divided into high and low expression groups, and differential expression analysis between them was performed. Functional enrichment analysis of differential expression genes (DEGs) was conducted. Univariate Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal prognostic DEGs. Then we established the prognostic model. A Nomogram model was constructed to predict the overall survival (OS) probability of LUAD patients. Results: CT83 expression was significantly correlated to the prognosis of LUAD patients. A total of 59 DEGs were identified, and a predictive model was constructed based on six optimal CT83-related DEGs, including CPS1, RHOV, TNNT1, FAM83A, IGF2BP1, and GRIN2A, could effectively predict the prognosis of LUAD patients. The nomogram could reliably predict the OS of LUAD patients. Moreover, the six important immune checkpoints (CTLA4, PD1, IDO1, TDO2, LAG3, and TIGIT) were closely correlated with the Risk Score, which was also differentially expressed between the LUAD samples with high and low-Risk Scores, suggesting that the poor prognosis of LUAD patients with high-Risk Score might be due to the immunosuppressive microenvironments. Conclusion: A prognostic model based on six optimal CT83 related genes could effectively predict the prognosis of LUAD patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tuo Liang ◽  
Jiarui Chen ◽  
GuoYong Xu ◽  
Zide Zhang ◽  
Jiang Xue ◽  
...  

AbstractWe established a relationship among the immune-related genes, tumor-infiltrating immune cells (TIICs), and immune checkpoints in patients with osteosarcoma. The gene expression data for osteosarcoma were downloaded from UCSC Xena and GEO database. Immune-related differentially expressed genes (DEGs) were detected to calculate the risk score. “Estimate” was used for immune infiltrating estimation and “xCell” was used to obtain 64 immune cell subtypes. Furthermore, the relationship among the risk scores, immune cell subtypes, and immune checkpoints was evaluated. The three immune-related genes (TYROBP, TLR4, and ITGAM) were selected to establish a risk scoring system based on their integrated prognostic relevance. The GSEA results for the Hallmark and KEGG pathways revealed that the low-risk score group exhibited the most gene sets that were related to immune-related pathways. The risk score significantly correlated with the xCell score of macrophages, M1 macrophages, and M2 macrophages, which significantly affected the prognosis of osteosarcoma. Thus, patients with low-risk scores showed better results with the immune checkpoints inhibitor therapy. A three immune-related, gene-based risk model can regulate macrophage activation and predict the treatment outcomes the survival rate in osteosarcoma.


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