scholarly journals An immune-related pseudogene signature to improve prognosis prediction of endometrial carcinoma patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Shanshan Tang ◽  
Yiyi Zhuge
Keyword(s):  
Cancer Treatment ◽  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Prognostic Significance ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Multiple Cancer

Abstract Background Pseudogenes show multiple functions in various cancer types, and immunotherapy is a promising cancer treatment. Therefore, this study aims to identify immune-related pseudogene signature in endometrial cancer (EC). Methods Gene transcriptome data of EC tissues and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) through UCSC Xena browser. Spearman correlation analysis was performed to identify immune-related pseudogenes (IRPs) between the immune genes and pseudogenes. Univariate Cox regression, LASSO, and multivariate were performed to develop a risk score signature to investigate the different overall survival (OS) between high- and low-risk groups. The prognostic significance of the signature was assessed by the Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC) curve. The abundance of 22 immune cell subtypes of EC patients was evaluated using CIBERSORT. Results Nine IRPs were used to build a prognostic signature. Survival analysis revealed that patients in the low-risk group presented longer OS than those in the high-risk group as well as in multiple subgroups. The signature risk score was independent of other clinical covariates and was associated with several clinicopathological variables. The prognostic signature reflected infiltration by multiple types of immune cells and revealed the immunotherapy response of patients with anti-programmed death-1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) therapy. Function enrichment analysis revealed that the nine IRPs were mainly involved in multiple cancer-related pathways. Conclusion We identified an immune-related pseudogene signature that was strongly correlated with the prognosis and immune response to EC. The signature might have important implications for improving the clinical survival of EC patients and provide new strategies for cancer treatment.

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 Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pu Wu ◽  
Jinyuan Shi ◽  
Wei Sun ◽  
Hao Zhang
Keyword(s):  
Thyroid Cancer ◽  
Risk Score ◽  
Prognostic Model ◽  
Immune Cell ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Risk Groups ◽  
Low Risk ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Pyroptosis is a form of programmed cell death triggered by inflammasomes. However, the roles of pyroptosis-related genes in thyroid cancer (THCA) remain still unclear. Objective This study aimed to construct a pyroptosis-related signature that could effectively predict THCA prognosis and survival. Methods A LASSO Cox regression analysis was performed to build a prognostic model based on the expression profile of each pyroptosis-related gene. The predictive value of the prognostic model was validated in the internal cohort. Results A pyroptosis-related signature consisting of four genes was constructed to predict THCA prognosis and all patients were classified into high- and low-risk groups. Patients with a high-risk score had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) of the receiver operator characteristic (ROC) curves assessed and verified the predictive performance of this signature. Multivariate analysis showed the risk score was an independent prognostic factor. Tumor immune cell infiltration and immune status were significantly higher in low-risk groups, which indicated a better response to immune checkpoint inhibitors (ICIs). Of the four pyroptosis-related genes in the prognostic signature, qRT-PCR detected three of them with significantly differential expression in THCA tissues. Conclusion In summary, our pyroptosis-related risk signature may have an effective predictive and prognostic capability in THCA. Our results provide a potential foundation for future studies of the relationship between pyroptosis and the immunotherapy response.

scholarly journals Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9621
Author(s):  
Shanliang Zhong ◽  
Huanwen Chen ◽  
Sujin Yang ◽  
Jifeng Feng ◽  
Siying Zhou
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Risk Group ◽  
Breast Cancer Survival ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Breast Cancer Patients ◽  
Prognostic Signature

We aimed to identify prognostic signature based on autophagy-related genes (ARGs) for breast cancer patients. The datasets of breast cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to construct multiple-ARG risk signature. In total, 32 ARGs were identified as differentially expressed between tumors and adjacent normal tissues based on TCGA. Six ARGs (IFNG, TP63, PPP1R15A, PTK6, EIF4EBP1 and NKX2-3) with non-zero coefficient were selected from the 32 ARGs using LASSO regression. The 6-ARG signature divided patients into high-and low-risk group. Survival analysis indicated that low-risk group had longer survival time than high-risk group. We further validated the 6-ARG signature using dataset from GEO and found similar results. We analyzed the associations between ARGs and breast cancer survival in TCGA and nine GEO datasets, and obtained 170 ARGs with significant associations. EIF4EBP1, FOS and FAS were the top three ARGs with highest numbers of significant associations. EIF4EBP1 may be a key ARG which had a higher expression level in patients with more malignant molecular subtypes and higher grade breast cancer. In conclusion, our 6-ARG signature was of significance in predicting of overall survival of patients with breast cancer. EIF4EBP1 may be a key ARG associated with breast cancer survival.

scholarly journals Integrated analysis of 1804 samples of six centers to construct and validate a robust immune-related prognostic signature associated with stromal cell abundance in tumor microenvironment for gastric cancer

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Junyu Huo ◽  
Ge Guan ◽  
Jinzhen Cai ◽  
Liqun Wu
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Risk Score ◽  
Stromal Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Integrated Analysis ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Stromal cells in tumor microenvironment could promote immune escape through a variety of mechanisms, but there are lacking research in the field of gastric cancer (GC). Methods We identified differential expressed immune-related genes (DEIRGs) between the high- and low-stromal cell abundance GC samples in The Cancer Genome Atlas and GSE84437 datasets. A risk score was constructed basing on univariate cox regression analysis, LASSO regression analysis, and multivariate cox regression analysis in the training cohort (n=772). The median value of the risk score was used to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE26253, n=432; GSE62254, n=300; GSE15459, n=191; GSE26901, n=109) from the Gene Expression Omnibus (GEO) database. The immune cell infiltration was quantified by the CIBERSORT method. Results The risk score contained 6 genes (AKT3, APOD, FAM19A5, LTBP3, NOV, and NOX4) showed good performance in predicting 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate of GC patients. The risk death and recurrence of GC patients growing with the increasing risk score. The patients were clustered into three subtypes according to the infiltration of 22 kinds of immune cells quantified by the CIBERSORT method. The proportion of cluster A with the worst prognosis in the high-risk group was significantly higher than that in the low-risk group; the risk score of cluster C subtype with the best prognosis was significantly lower than that of the other two subtypes. Conclusion This study established and validated a robust prognostic model for gastric cancer by integrated analysis 1804 samples of six centers, and its mechanism was explored in combination with immune cell infiltration characterization.

scholarly journals Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Zhu ◽  
Yong Mou ◽  
Shenglan Ye ◽  
Hongling Hu ◽  
Rujuan Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Survival Analysis ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Prognostic Signature ◽  
Kaplan Meier ◽  
Immune Cell Infiltrates

Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

scholarly journals Development and validation of Pyroptosis‑related lncRNAs prediction model for bladder cancer

2022 ◽  
Author(s):  
Thongher Lia ◽  
Yanxiang Shao ◽  
Parbatraj Regmi ◽  
Xiang Li
Keyword(s):  
Bladder Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Bladder cancer is one of the highly heterogeneous disorders accompanied by a poor prognosis. This study aimed to construct a model based on pyroptosis‑related lncRNA to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis‑related lncRNAs were identified by utilizing a co-expression network of Pyroptosis‑related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, 8 pyroptosis-related lncRNA markers were established using Lasso regression and multivariate Cox regression analysis. Patients were separated into high and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (p < 0.001), and In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS ( HR>1, P<0.01). The area under the curve (AUC) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739 respectively. In conclusion, these 8 pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.

scholarly journals Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
M2 Macrophages ◽  
Regression Analyses ◽  
Prognostic Signature ◽  
Training Cohort

Background. An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated. Methods. Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, n = 300 ; GSE15459, n = 191 ; and GSE26901, n = 109 ). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort ( n = 600 ) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, n = 432 ; GSE84437, n = 431 ; and TCGA, n = 336 ). Immune cell infiltration (ICI) was quantified by the CIBERSORT method. Results. A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort ( AUC > 0.7 ). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC ( p < 0.001 ). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group ( p < 0.001 ), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor ( p = 0.011 ). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score ( p = 0.00085 ). The patients’ risk score increased with the progression of the clinicopathological stage. Conclusion. In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.

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.

scholarly journals Identification of a Novel Eight-lncRNA Prognostic Signature for HBV-HCC and Analysis of Their Functions Based on Coexpression and ceRNA Networks

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xiaonan Zhao ◽  
Zhenzi Bai ◽  
Chenghua Li ◽  
Chuanlun Sheng ◽  
Hongyan Li
Keyword(s):  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Survival Curve ◽  
Characteristic Curve ◽  
The Cancer Genome Atlas ◽  
Good Prediction ◽  
Prognostic Signature ◽  
Training Set ◽  
Validation Set

Studies have demonstrated the prognosis potential of long noncoding RNAs (lncRNAs) for hepatocellular carcinoma (HCC), but specific lncRNAs for hepatitis B virus- (HBV-) related HCC have rarely been reported. This study was aimed at identifying a lncRNA prognostic signature for HBV-HCC and exploring their underlying functions. The sequencing dataset was collected from The Cancer Genome Atlas database as the training set, while the microarray dataset was obtained from the European Bioinformatics Institute database (E-TABM-36) as the validation set. Univariate and multivariate Cox regression analyses identified that eight lncRNAs (TSPEAR-AS1, LINC00511, LINC01136, MKLN1-AS, LINC00506, KRTAP5-AS1, ZNF252P-AS1, and THUMPD3-AS1) were significantly associated with overall survival (OS). These eight lncRNAs were used to construct a risk score model. The Kaplan-Meier survival curve results showed that this risk score can significantly differentiate the OS between the high-risk group and the low-risk group. Receiver operating characteristic curve analysis demonstrated that this risk score exhibited good prediction effectiveness (area under the curve AUC=0.990 for the training set; AUC=0.903 for the validation set). Furthermore, this lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis after adjusting other clinical characteristics. The crucial coexpression (LINC00511-CABYR, THUMPD3-AS1-TRIP13, LINC01136-SFN, LINC00506-ANLN, and KRTAP5-AS1/TSPEAR-AS1/MKLN1-AS/ZNF252P-AS1-MC1R) or competing endogenous RNA (THUMPD3-AS1-hsa-miR-450a-TRIP13) interaction axes were identified to reveal the possible functions of lncRNAs. These genes were enriched into cell cycle-related biological processes or pathways. In conclusion, our study identified a novel eight-lncRNA prognosis signature for HBV-HCC patients and these lncRNAs may be potential therapeutic targets.

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