scholarly journals Comprehensive Analysis and Identification of an Immune-Related Gene Signature with Prognostic Value for Prostate Cancer

2021 ◽  
Vol Volume 14 ◽  
pp. 2931-2942
Author(s):  
Yongrui Zhang ◽  
Yaowen Fu
2020 ◽  
Vol 11 ◽  
Author(s):  
Qijie Zhang ◽  
Kai Zhao ◽  
Lebin Song ◽  
Chengjian Ji ◽  
Rong Cong ◽  
...  

Background: Nowadays, predictions of biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) are mainly based on clinical parameters with a low predictive accuracy. Given the critical role of apoptosis in PCa occurrence and progression, we aimed to establish a novel predictive model based on apoptosis-related gene signature and clinicopathological parameters that can improve risk stratification for BCR and assist in clinical decision-making.Methods: Expression data and corresponding clinical information were obtained from four public cohorts, one from The Cancer Genome Atlas (TCGA) dataset and three from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis (WGCNA) was performed to identify candidate modules closely correlated to BCR, and univariate and multivariate Cox regression analyses were utilized to build the gene signature. Time-dependent receiver operating curve (ROC) and Kaplan–Meier (KM) survival analysis were used to assess the prognostic value. Finally, we analyzed the expression of genes in the signature and validated the results using quantitative real-time PCR (qRT-PCR).Results: The novel gene signature we established exhibited a high prognostic value and was able to act as an independent risk factor for BCR [Training set: P < 0.001, hazard ratio (HR) = 7.826; Validation set I: P = 0.006, HR = 2.655; Validation set II: P = 0.003, HR = 4.175; Validation set III: P < 0.001, HR = 3.008]. Nomogram based on the gene signature and clinical parameters was capable of distinguishing high-risk BCR patients. Additionally, functional enrichment analysis showed several enriched pathways and biological processes, which might help reveal the underlying mechanism. The expression results of qRT-PCR were consistent with TCGA results.Conclusion: The apoptosis-related gene signature could serve as a powerful predictor and risk factor for BCR in localized PCa patients after RP.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Jin ◽  
Jun Wang ◽  
Lina Ge ◽  
Qing Hu

Objective: Sciatica pertains to neuropathic pain that has been associated with inflammatory response. We aimed to identify significant immune-related biomarkers for sciatica in peripheral blood.Methods: We utilized the GSE150408 expression profiling data from the Gene Expression Omnibus (GEO) database as the training dataset and extracted immune-related genes for further analysis. Differentially expressed immune-related genes (DEIRGs) between healthy controls and patients with sciatica were selected using the “limma” package and verified in clinical specimens by quantitative reverse transcription PCR (RT-qPCR). A diagnostic immune-related gene signature was established using the training model and random forest (RF), generalized linear model (GLM), and support vector machine (SVM) models. Sciatica patient subtypes were identified using the consensus clustering method.Results: Thirteen significant DEIRGs were acquired, of which five (CRP, EREG, FAM19A4, RLN1, and WFIKKN1) were selected to establish a diagnostic immune-related gene signature according to the most appropriate training model, namely, the RF model. A clinical application nomogram model was established based on the expression level of the five DEIRGs. The sciatica patients were divided into two subtypes (C1 and C2) according to the consensus clustering method.Conclusions: Our research established a diagnostic five immune-related gene signature to discriminate sciatica and identified two sciatica subtypes, which may be beneficial to the clinical diagnosis and treatment of sciatica.


2020 ◽  
Vol 184 (2) ◽  
pp. 325-334
Author(s):  
Ji-Yeon Kim ◽  
Hae Hyun Jung ◽  
Insuk Sohn ◽  
Sook Young Woo ◽  
Hyun Cho ◽  
...  

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097711
Author(s):  
Jiasheng Lei ◽  
Dengyong Zhang ◽  
Chao Yao ◽  
Sheng Ding ◽  
Zheng Lu

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.


2020 ◽  
Vol 72 (9-10) ◽  
pp. 455-465
Author(s):  
Mengnan Zhao ◽  
Ming Li ◽  
Zhencong Chen ◽  
Yunyi Bian ◽  
Yuansheng Zheng ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Siqi Dai ◽  
Shuang Xu ◽  
Yao Ye ◽  
Kefeng Ding

BackgroundDespite recent advance in immune therapy, great heterogeneity exists in the outcomes of colorectal cancer (CRC) patients. In this study, we aimed to analyze the immune-related gene (IRG) expression profiles from three independent public databases and develop an effective signature to forecast patient’s prognosis.MethodsIRGs were collected from the ImmPort database. The CRC dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another two CRC datasets from the Gene Expression Omnibus (GEO). Gene function enrichment analysis was conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.ResultsThe three datasets had 487, 579, and 224 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B, and IL20RB) was developed through feature selection that showed good differentiation between the low- and high-risk groups in the training set (p &lt; 0.001), which was later confirmed in the two validation groups (log-rank p &lt; 0.05). The signature outperformed tumor TNM staging for survival prediction. GO and KEGG functional annotation analysis suggested that the signature was significantly enriched in metabolic processes and regulation of immunity (p &lt; 0.05). When combined with clinical risk factors, the model showed robust prediction capability.ConclusionThe immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could provide insight for personalized cancer management.


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