Stromal Score-Based Gene Signature: A Prognostic Prediction Model for Colon Cancer

BackgroundGrowing evidence has revealed the crucial roles of stromal cells in the microenvironment of various malignant tumors. However, efficient prognostic signatures based on stromal characteristics in colon cancer have not been well-established yet. The present study aimed to construct a stromal score-based multigene prognostic prediction model for colon cancer.MethodsStromal scores were calculated based on the expression profiles of a colon cancer cohort from TCGA database applying the ESTIMATE algorithm. Linear models were used to identify differentially expressed genes between low-score and high-score groups by limma R package. Univariate, LASSO, and multivariate Cox regression models were used successively to select the prognostic gene signature. Two independent datasets from GEO were used as external validation cohorts.ResultsLow stromal score was demonstrated to be a favorable factor to the overall survival of colon cancer patients in TCGA cohort (p = 0.0046). Three hundred and seven stromal score-related differentially expressed genes were identified. Through univariate, LASSO, and multivariate Cox regression analyses, a gene signature consisting of LEP, NOG, and SYT3 was recognized to build a prognostic prediction model. Based on the predictive values estimated by the established integrated model, patients were divided into two groups with significantly different overall survival outcomes (p < 0.0001). Time-dependent Receiver operating characteristic curve analyses suggested the satisfactory predictive efficacy for the 5-year overall survival of the model (AUC value = 0.733). A nomogram with great predictive performance combining the multigene prediction model and clinicopathological factors was developed. The established model was validated in an external cohort (AUC value = 0.728). In another independent cohort, the model was verified to be of significant prognostic value for different subgroups, which was demonstrated to be especially accurate for young patients (AUC value = 0.763).ConclusionThe well-established model based on stromal score-related gene signature might serve as a promising tool for the prognostic prediction of colon cancer.

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Stromal Score-based Gene Signature: A Prognostic Prediction Model for Colon Cancer

10.21203/rs.3.rs-125354/v1 ◽

2020 ◽

Author(s):

Jing Jia ◽

Yuhan Dai ◽

Qing Zhang ◽

Peiyu Tang ◽

Qiang Fu ◽

...

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Prediction Model ◽

Differentially Expressed Genes ◽

Gene Signature ◽

Rank Test ◽

Regression Analyses ◽

Log Rank Test ◽

Auc Value ◽

Prognostic Prediction

Abstract BackgroundGrowing evidence has revealed the crucial roles of stromal cells in the microenvironment of various malignant tumors. However, efficient prognostic signatures based on stromal characteristics in colon cancer have not been well-established yet. The present study aimed to construct a stromal score-based multigene prognostic prediction model for colon cancer.MethodStromal scores were calculated based on the expression profiles of a colon cancer cohort from TCGA database applying the ESTIMATE algorithm. Linear models were used to identify differentially expressed genes between low-score and high-score groups by limma R package. Univariate and multivariate CoxPH regression analyses were used successively to select prognostic gene signature. An independent dataset from GEO was used as a validation cohort.ResultsLow stromal score was demonstrated to be a favorable factor to overall survival of colon cancer patients in TCGA cohort (log-rank test p = 0.0046). Three hundred and seven stromal score-related differentially expressed genes were identified. Through univariate and multivariate CoxPH regression analyses, a gene signature consisting of LEP, SYT3, NOG and IGSF11 was recognized to build a prognostic prediction model. Based on the predictive values estimated by the established integrated model, patients were divided into two groups with significantly different overall survival outcomes (log-rank test p < 0.0001). Time-dependent Receiver operating characteristic curve analyses suggested the satisfactory predictive efficacy for 5-year overall survival of the model (AUC value = 0.736). A nomogram with great predictive performance combining the multigene prediction model and clinicopathological factors was developed. The established model was verified to be of significant prognostic value for different subgroups in an independent colon cancer cohort from GEO database, which was demonstrated to be especially accurate for young patients (AUC value = 0.752). ConclusionThe well-established model based on stromal score-related gene signature might serve as a promising tool for the prognostic prediction of colon cancer.

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Development of a Prognostic Gene Signature For Hepatocellular Carcinoma

10.21203/rs.3.rs-107220/v1 ◽

2020 ◽

Author(s):

Cuiyun Wu ◽

Yaosheng Luo ◽

Yinghui Chen ◽

Hongling Qu ◽

Lin Zheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Differentially Expressed Genes ◽

Cox Regression ◽

Risk Group ◽

Gene Signature ◽

Differentially Expressed ◽

Risk Scores ◽

Prognostic Gene ◽

Prognostic Gene Signature

Abstract Background: Accurate prediction of overall survival is important for prognosis and the assignment of appropriate personalized clinical treatment in hepatocellular carcinoma (HCC) patients. The aim of the present study was to establish an optimal gene model for the independent prediction of prognosis associated with common clinical patterns.Methods: Gene expression profiles and the corresponding clinical information of the LIHC cohort were obtained from The Cancer Genome Atlas. Differentially expressed genes were found using the R package “limma”. Subsequently, a prognostic gene signature was developed using the LASSO Cox regression model. Kaplan–Meier, log-rank, and receiver operating characteristic (ROC) analyses were performed to verify the predictive accuracy of the prognostic model. Finally, a nomogram and calibration plot were created using the “rms” package.Results: Differentially expressed genes were screened with threshold criteria (FDR < 0.01 and |log FC|>3) and 563 differentially expressed genes were obtained, including 448 downregulated and 115 upregulated genes. Using the LASSO Cox regression model, a prognostic gene signature was developed based on nine genes,IQGAP3, BIRC5, PTTG1, STC2, CDKN3, PBK, EXO1, NEIL3, and HOXD9, the expression levels of which were quantitated using RT-qPCR. According to the risk scores, patients were separated into high-risk and low-risk groups. Patients with lower risk scores generally had a better survival rate than those with higher risk scores. The mortality rate in the high-risk group was 42.02%, while that in the low-risk group was 12.50%. Results of the log-rank test showed significant differences in mortality between the two groups (HR: 4.86; 95% CI: 2.72–8.69; P = 1.01E-08). Subsequently, we assessed the prognostic accuracy of the gene signature using an ROC curve and the results show good sensitivity and specificity, with an average area under the curve (AUC) of 0.81 at 5 years (P < 0.01). Following multivariate adjustment for conventional clinical patterns, the prognostic gene signature remained a powerful and independent factor (HR: 4.70; 95% CI: 2.61–8.38; P = 2.06E-07), confirming its robust predictive ability of overall survival in HCC patients. Finally, a nomogram was established based on the gene signature and four clinicopathological features, which demonstrated an advantageous discriminating ability with the potential to facilitate clinical decision-making in HCC.Conclusion: Our prognostic gene signature can be used as a combined biomarker for the independent prediction of overall survival in HCC patients. Moreover, we created a nomogram that can be used to infer prognosis and aid individualized decisions regarding treatment and surveillance.

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Identification and Validation of a Glycolysis Related Metabolic Reprogramming Gene Signature for Predicting Survival in Colon Cancer Patients

10.21203/rs.3.rs-916034/v1 ◽

2021 ◽

Author(s):

Gang Liu ◽

Xiaowang WU ◽

Jian Chen

Keyword(s):

Colon Cancer ◽

Prediction Model ◽

Cox Regression ◽

Malignant Tumors ◽

Gene Signature ◽

Metabolic Reprogramming ◽

Risk Scores ◽

Cox Regression Analysis ◽

Prognosis Model ◽

The Relationship

Abstract Background Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with high mortality rate. Because of malignancy and easily metastasis feather, and limited treatments, the prognosis of CC remains poor. Glycolysis is a metabolic process of glucose in anoxic environments which is an important way to provide energy for tumor. The role of glycolysis in CC largely remains unknown and is necessary to be explored. Method In our study, we analyzed glycolysis related genes expression in CC, patients gene expression and corresponding clinical data were downloaded from GEO dataset, glycolysis related genes sets were collected from Msigdb. Through COX regression analysis, prognosis model based on glycolysis-related genes was established. The efficacy of gene model was tested by Survival analysis, ROC analysis and PCA analysis. Furthermore, the relationship between risk scores and clinical characteristic was researched. Results Our findings identified 13 glycolysis related genes (NUP107, SEC13, ALDH7A1, ALG1, CHPF, FAM162A, FBP2, GALK1, IDH1, TGFA, VLDLR, XYLT2 and OGDHL) consisted prognostic prediction model with relative high accuracy. The relationship between prediction model and clinical feathers were specifically studied, results showed age > 65years, TNM III-IV, T3-4, N1-3, M1 and high-risk score were independent prognostic risk factors with poorer prognosis. Finally, model genes were significantly expressed and EMT were activated in CC patients. Conclusion This study provided a new aspect to advance our understanding in the potential mechanism of glycolysis in CC.

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Development of a Predictive Immune-Related Gene Signature Associated With Hepatocellular Carcinoma Patient Prognosis

Cancer Control ◽

10.1177/1073274820977114 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327482097711

Author(s):

Jiasheng Lei ◽

Dengyong Zhang ◽

Chao Yao ◽

Sheng Ding ◽

Zheng Lu

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

R Package ◽

Gene Signature ◽

Differentially Expressed ◽

Related Gene ◽

Patient Cohort ◽

Immune Related Gene ◽

Related Risk

Background: Hepatocellular carcinoma (HCC) remains the third leader cancer-associated cause of death globally, but the etiological basis for this complex disease remains poorly clarified. The present study was thus conceptualized to define a prognostic immune-related gene (IRG) signature capable of predicting immunotherapy responsiveness and overall survival (OS) in patients with HCC. Methods: Five differentially expressed IRG associated with HCC were established the immune-related risk model through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Patients were separated at random into training and testing cohorts, after which the association between the identified IRG signature and OS was evaluated using the “survival” R package. In addition, maftools was leveraged to assess mutational data, with tumor mutation burden (TMB) scores being calculated as follows: (total mutations/total bases) × 106. Immune-related risk term abundance was quantified via “ssGSEA” algorithm using the “gsva” R package. Results: HCC patients were successfully stratified into low-risk and high-risk groups based upon a signature composed of 5 differentially expressed IRGs, with overall survival being significantly different between these 2 groups in training cohort, testing cohort and overall patient cohort ( P = 1.745e-06, P = 1.888e-02, P = 4.281e-07). No association was observed between TMB and this IRG risk score in the overall patient cohort ( P = 0.461). Notably, 19 out of 29 immune-related risk terms differed substantially in the overall patient dataset. These risk terms mainly included checkpoints, human leukocyte antigens, natural killer cells, dendritic cells, and major histocompatibility complex class I. Conclusion: In summary, an immune-related prognostic gene signature was successfully developed and used to predict survival outcomes and immune system status in patients with HCC. This signature has the potential to help guide immunotherapeutic treatment planning for patients affected by this deadly cancer.

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A Novel Seventeen-Gene Metabolic Signature for Predicting Prognosis in Colon Cancer

BioMed Research International ◽

10.1155/2020/4845360 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Dakui Luo ◽

Zezhi Shan ◽

Qi Liu ◽

Sanjun Cai ◽

Qingguo Li ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Differentially Expressed ◽

Metabolic Signature ◽

Metabolic Genes ◽

Prognostic Prediction

A metabolic disorder is considered one of the hallmarks of cancer. Multiple differentially expressed metabolic genes have been identified in colon cancer (CC), and their biological functions and prognostic values have been well explored. The purpose of the present study was to establish a metabolic signature to optimize the prognostic prediction in CC. The related data were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, and Gene Expression Omnibus (GEO) combined with GSE39582 set, GSE17538 set, GSE33113 set, and GSE37892 set. The differentially expressed metabolic genes were selected for univariate Cox regression and lasso Cox regression analysis using TCGA and GTEx datasets. Finally, a seventeen-gene metabolic signature was developed to divide patients into a high-risk group and a low-risk group. Patients in the high-risk group presented poorer prognosis compared to the low-risk group in both TCGA and GEO datasets. Moreover, gene set enrichment analyses demonstrated multiple significantly enriched metabolism-related pathways. To sum up, our study described a novel seventeen-gene metabolic signature for prognostic prediction of colon cancer.

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Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9978206 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yang Li ◽

Rongrong Sun ◽

Rui Li ◽

Yonggang Chen ◽

He Du

Keyword(s):

Overall Survival ◽

Regression Analysis ◽

Lung Adenocarcinoma ◽

Regulatory Mechanism ◽

Cox Regression ◽

Gene Signature ◽

Differentially Expressed ◽

Prognostic Signature ◽

Cox Regression Analysis ◽

Cerna Network

Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009 ). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004 ). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C -indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.

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A Novel Ferroptosis-Related Gene Signature Predicts Overall Survival of Breast Cancer Patients

Biology ◽

10.3390/biology10020151 ◽

2021 ◽

Vol 10 (2) ◽

pp. 151

Author(s):

Haifeng Li ◽

Lu Li ◽

Cong Xue ◽

Riqing Huang ◽

Anqi Hu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prediction Model ◽

Risk Score ◽

Cox Regression ◽

Gene Prediction ◽

Clinical Information ◽

Risk Groups ◽

Gene Signature ◽

Breast Cancer Patients

Breast cancer is the second leading cause of death in women, thus a reliable prognostic model for overall survival (OS) in breast cancer is needed to improve treatment and care. Ferroptosis is an iron-dependent cell death. It is already known that siramesine and lapatinib could induce ferroptosis in breast cancer cells, and some ferroptosis-related genes were closely related with the outcomes of treatments regarding breast cancer. The relationship between these genes and the prognosis of OS remains unclear. The data of gene expression and related clinical information was downloaded from public databases. Based on the TCGA-BRCA cohort, an 8-gene prediction model was established with the least absolute shrinkage and selection operator (LASSO) cox regression, and this model was validated in patients from the METABRIC cohort. Based on the median risk score obtained from the 8-gene model, patients were stratified into high- or low-risk groups. Cox regression analyses identified that the risk score was an independent predictor for OS. The findings from CIBERSORT and ssGSEA presented noticeable differences in enrichment scores for immune cells and pathways between the abovementioned two risk groups. To sum up, this prediction model has potential to be widely applied in future clinical settings.

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Identification of a circadian gene signature that predicts overall survival in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.11733 ◽

2021 ◽

Vol 9 ◽

pp. e11733

Author(s):

Xinliang Gao ◽

Mingbo Tang ◽

Suyan Tian ◽

Jialin Li ◽

Wei Liu

Keyword(s):

Overall Survival ◽

Regression Analysis ◽

Lung Adenocarcinoma ◽

Circadian Clock ◽

Cox Regression ◽

Gene Signature ◽

Differentially Expressed ◽

Circadian Gene ◽

Cox Regression Analysis ◽

Circadian Genes

Background Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer which is the leading cause of death in cancer patients. Circadian clock disruption has been listed as a likely carcinogen. However, whether the expression of circadian genes affects overall survival (OS) in LUAD patients remains unknown. In this article, we identified a circadian gene signature to predict overall survival in LUAD. Methods RNA sequencing (HTSeq-FPKM) data and clinical characteristics were obtained for a cohort of LUAD patients from The Cancer Genome Atlas (TCGA). A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database. Results Five differentially expressed genes (DEGs) were identified to be significantly associated with OS using univariate Cox proportional regression analysis (P < 0.05). Patients classified as high risk based on these five DEGs had significantly lower OS than those classified as low risk in both the TGCA cohort and GSE72094 dataset (P < 0.001). Multivariate Cox regression analysis revealed that the five-gene-signature based risk score was an independent predictor of OS (hazard ratio > 1, P < 0.001). Receiver operating characteristic (ROC) curves confirmed its prognostic value. Gene set enrichment analysis (GSEA) showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cell proliferation, gene damage repair, proteasomes, and immune and autoimmune diseases were significantly enriched. Conclusion A novel circadian gene signature for OS in LUAD was found to be predictive in both the derivation and validation cohorts. Targeting circadian genes is a potential therapeutic option in LUAD.

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Identifying a cervical cancer survival signature based on mRNA expression and genome-wide copy number variations

Experimental Biology and Medicine ◽

10.1177/15353702211053580 ◽

2021 ◽

pp. 153537022110535

Author(s):

Nan Li ◽

Kai Yu ◽

Zhong Lin ◽

Dingyuan Zeng

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Differentially Expressed Genes ◽

Risk Score ◽

Copy Number ◽

Gene Signature ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Prognostic Signature ◽

Immune Score

Cervical cancer mortality is the second highest in gynecological cancers. This study developed a new model based on copy number variation data and mRNA data for overall survival prediction of cervical cancer. Differentially expressed genes from The Cancer Genome Atlas dataset detected by univariate Cox regression analysis were further simplified to six by least absolute shrinkage and selection operator (Lasso) and stepwise Akaike information criterion (stepAIC). The study developed a six-gene signature, which was further verified in independent dataset. Association between immune infiltration and risk score was investigated by immune score. The relation between the signature and functional pathways was examined by gene set enrichment analysis. Ninety-nine differentially expressed genes were detected, and C11orf80, FOXP3, GSN, HCCS, PGAM5, and RIBC2 were identified as key genes to construct a six-gene signature. The prognostic signature showed a significant correlation with overall survival (hazard ratio, HR = 3.45, 95% confidence interval (CI) = 2.08–5.72, p < 0.00001). Immune score showed a negative correlation with the risk score calculated by the signature ( p < 0.05). Four immune-related pathways were closely associated with risk score ( p < 0.0001). The six-gene prognostic signature was an effective tool to predict overall survival of cervical cancer. In conclusion, the newly identified six genes may be considered as new drug targets for cervical cancer treatment.

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A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Bladder cancer

10.21203/rs.3.rs-333257/v1 ◽

2021 ◽

Author(s):

Liyuan Wu ◽

Feiya Yang ◽

Nianzeng Xing

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Gene Signature ◽

Survival Prediction ◽

Related Gene ◽

Cox Regression Analysis ◽

Prognostic Prediction

Abstract Background Bladder cancer (BC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis is related to a variety of biological pathways, including those involved in the metabolism of amino acids, lipids, and iron. However, the prognostic value of ferroptosis-related genes in BC remains to be further elucidated. Methods In this study, the mRNA expression profiles and corresponding clinical data of BC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature and validated it. Results Our results showed 12 differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 9-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups, especially in humoral immune response process. Conclusion In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in BC. Targeting ferroptosis may be a therapeutic alternative for BC.

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