scholarly journals Identification of Cross-Talk and Pyroptosis-Related Genes Linking Periodontitis and Rheumatoid Arthritis Revealed by Transcriptomic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-29
Author(s):  
Yongbin Jing ◽  
Dong Han ◽  
Chunyang Xi ◽  
Jinglong Yan ◽  
Jinpeng Zhuang

Background. The current study is aimed at identifying the cross-talk genes between periodontitis (PD) and rheumatoid arthritis (RA), as well as the potential relationship between cross-talk genes and pyroptosis-related genes. Methods. Datasets for the PD (GSE106090, GSE10334, GSE16134) and RA (GSE55235, GSE55457, GSE77298, and GSE1919) were downloaded from the GEO database. After batch correction and normalization of datasets, differential expression analysis was performed to identify the differentially expressed genes (DEGs). The cross-talk genes linking PD and RA were obtained by overlapping the DEGs dysregulated in PD and DEGs dysregulated in RA. Genes involved in pyroptosis were summarized by reviewing literatures, and the correlation between pyroptosis genes and cross-talk genes was investigated by Pearson correlation coefficient. Furthermore, the weighted gene coexpression network analysis (WGCNA) was carried out to identify the significant modules which contained both cross-talk genes and pyroptosis genes in both PD data and RA data. Thus, the core cross-talk genes were identified from the significant modules. Receiver-operating characteristic (ROC) curve analysis was performed to identify the predictive accuracy of these core cross-talk genes in diagnosing PD and RA. Based on the core cross-talk genes, the experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. Results. A total of 40 cross-talk genes were obtained. Most of the pyroptosis genes were not differentially expressed in disease and normal samples. By selecting the modules containing both cross-talk genes or pyroptosis genes, the blue module was identified to be significant module. Three genes, i.e., cross-talk genes (TIMP1, LGALS1) and pyroptosis gene-GPX4, existed in the blue module of PD network, while two genes (i.e., cross-talk gene-VOPP1 and pyroptosis gene-AIM2) existed in the blue module of RA network. ROC curve analysis showed that three genes (TIMP1, VOPP1, and AIM2) had better predictive accuracy in diagnosing disease compared with the other two genes (LGALS1 and GPX4). Conclusions. This study revealed shared mechanisms between RA and PD based on cross-talk and pyroptosis genes, supporting the relationship between the two diseases. Thereby, five modular genes (TIMP1, LGALS1, GPX4, VOPP1, and AIM2) could be of relevance and might serve as potential biomarkers. These findings are a basis for future research in the field.

2021 ◽  
Vol 8 ◽  
Author(s):  
Jieqing Yu ◽  
Xue Kang ◽  
Yuanping Xiong ◽  
Qing Luo ◽  
Daofeng Dai ◽  
...  

Introduction: Chronic rhinosinusitis (CRS) is often classified primarily on the basis of the absence or presence of nasal polyps (NPs), that is, as CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). Additionally, according to the percentage of eosinophils, CRSwNP can be further divided into eosinophilic CRSwNP (ECRSwNP) and non-ECRSwNP. CRSwNP is a significant public health problem with a considerable socioeconomic burden. Previous research reported that the pathophysiology of CRSwNP is a complex, multifactorial disease. There have been many studies on its etiology, but its pathogenesis remains unclear. Dysregulated expression of microRNAs (miRNAs) has been shown in psoriasis, rheumatoid arthritis, pulmonary fibrosis, and allergic asthma. Circular RNAs (circRNAs) are also involved in inflammatory diseases such as rheumatoid arthritis, septic acute kidney injury, myocardial ischemia/reperfusion injury, and sepsis-induced liver damage. The function of miRNAs in various diseases, including CRSwNP, is a research hotspot. In contrast, there have been no studies on circRNAs in CRSwNP. Overall, little is known about the functions of circRNAs and miRNAs in CRSwNP. This study aimed to investigate the expression of circRNAs and miRNAs in a CRSwNP group and a control group to determine whether these molecules are related to the occurrence and development of CRSwNP.Methods: Nine nasal mucosa samples were collected, namely, three ECRSwNP samples, three non-ECRSwNP samples, and three control samples, for genomic microarray analysis of circRNA and microRNA expression. All of the tissue samples were from patients who were undergoing functional endoscopic sinus surgery in our department. Then we selected some differentially expressed miRNAs and circRNAs for qPCR verification. Meanwhile, GO enrichment analysis and KEGG pathway analysis were applied to predict the biological functions of aberrantly expressed circRNAs and miRNAs based on the GO and KEGG databases. Receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA) were performed to confirm these molecules are involved in the occurrence and development of CRSwNP.Results: In total, 2,875 circRNAs showed significant differential expression in the CRSwNP group. Specifically, 1794 circRNAs were downregulated and 1,081 circRNAs were upregulated. In the CRSwNP group, the expression of 192 miRNAs was significantly downregulated, and none of the miRNAs were significantly upregulated. GO and KEGG analysis showed differential circRNAs and miRNAs were enriched in “amoebiasis,” “salivary secretion,” “pathways in cancer,” and “endocytosis.” Through qRT-PCR verification, the expression profiles of hsa-circ-0031593, hsa-circ-0031594, hsa-miR-132-3p, hsa-miR-145-5p, hsa-miR-146a-5p, and hsa-miR-27b-3p were shown to have statistical differences. In addition, ROC curve analysis showed that the molecules with the two highest AUCs were hsa-circ-0031593 with AUC 0.8353 and hsa-miR-145-5p with AUC 0.8690. Through PCA with the six ncRNAs, the first principal component explained variance ratio was 98.87%. The AUC of the six ncRNAs was 0.8657.Conclusion: In our study, the expression profiles of ECRSwNP and non-ECRSwNP had no statistical differences. The differentially expressed circRNAs and miRNAs between CRSwNP and control may play important roles in the pathogenesis of CRSwNP. Altered expression of hsa-circ-0031593 and hsa-miR-145-5p have the strongest evidence for involvement in the occurrence and development of CRSwNP because their AUCs are higher than the other molecules tested in this study.


2019 ◽  
Vol 45 (04) ◽  
pp. 348-355
Author(s):  
Gao Zhao-wei ◽  
Guan-hua Zhao ◽  
Rui-cheng Li ◽  
Hui-ping Wang ◽  
Chong Liu ◽  
...  

Abstract Objective The aim of this study was to evaluate the changes and diagnostic value of serum ADA activity in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and myasthenia gravis (MG). Methods Serum ADA activity, including total ADA (tADA) and its isoenzymes (ADA1 and ADA2), was determined in patients with different autoimmune diseases (144 RA, 114 SLE, 55 AS, 68 MG). The changes in serum ADA activity in patients were analysed. A receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of serum ADA activity. Results Compared with healthy controls, the serum tADA activity in SLE patients was significantly increased (p<0.001), while the serum tADA activity in patients with RA, AS and MG did not change (p>0.05). The ROC analysis showed that the optimal cut-off value of serum tADA activity for SLE diagnosis was 10.5 U/L (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693; p<0.001). Moreover, our results showed that there were no significant changes of ADA1 and ADA2 activity in RA, AS and MG patients, while the serum ADA2 activity was significantly increased in SLE patients. The ROC analysis showed that ADA2 activity could be used in diagnosing SLE with 75.4% specificity and 78.1% sensitivity (LR: 3.175). Based on the ROC curve analysis, serum tADA activity (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693) and ADA2 activity (75.4% specificity and 78.1% sensitivity; LR: 3.175) are unlikely to be used in diagnosing SLE. Furthermore, there was a positive correlation between tADA activity and SLE disease activity (r=0.303, p=0.010). Notably, serum tADA activity in SLE patients with arthritis was higher than in patients without arthritis (p=0.005), which suggests that tADA activity might be related to lupus arthritis. Conclusion These findings suggest that serum tADA and ADA2 activity might play an important role in SLE progression.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1313.2-1313
Author(s):  
R. Shumnalieva ◽  
D. Kachakova ◽  
T. Velikova ◽  
R. Kaneva ◽  
Z. Kolarov ◽  
...  

Background:Interleukin 17 (IL-17) is a proinflammatory cytokine, which overproduction promotes the autoimmune reaction in rheumatoid arthritis (RA). Posttranscriptional regulation of IL-17 by specific microRNAs (miRNAs) is of great interest in the recent years. 146a was associated with IL-17 expression in IL-17 producing T-cells in the synovium when miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by directly targeting the suppressor of cytokine signaling (SOCS) 1 [1, 2]. It has been shown that IL-17 production in lymphocytes or its function could be regulated by miR-223 by targeting Roquin ubiquitin ligase or its receptors [3].Objectives:To examine a possible correlation between systemic and local concentrations of IL-17A and systemic and local miR-146a, miR-155 and miR-223 expression in RA patients.Methods:Expression levels of three miRNAs were determined in matched peripheral blood (PB) and synovial fluid (SF) samples of RA patients by relative quantitation method 2-ΔΔCt. As reference control for normalization RNU6B gene was used. Concentrations of IL-17A were compared between matched serum and SF samples from 20 RA patients by Human IL-17A ELISA kit (Gene probe, Diaclone, France). Healthy donors were used as controls.Results:miR-146a, miR-155 and miR-223 showed overexpression in RA SF when compared to HCs SF (in 70.83%, p=0.007; in 79.17%, p=1.63x10-4and in 79.17%, p=1.64x10-3, respectively). The ROC curve analysis showed diagnostic accuracy for miR-146a in SF with AUC=0.769, p=0.006, AUC for SF miR-155 was 0.858, p=2.3x10-4and AUC for SF miR-223 was 0.841 p=4.6x10-4. SF levels of miR-146a and miR-155 were overexpressed in 52.17% and in 76.09% of the RA patients compared to its systemic levels. SF miR-223 was underexpressed in 58.7% of the patients compared to its systemic levels. Levels of IL-17A were higher in RA SF compared to serum (8.645 pg/ml versus 0.315 pg/ml, p=0.012). ROC curve analysis for SF IL-17A showed area under the curve (AUC) = 0.885, p<0.000.Conclusion:The difference between the systemic and local concentration of IL-17A and miRNAs expression shows that the inflammatory disease process leads to their altered expression with a possible role of these molecules in the disease pathogenesis. The higher local levels of miR-155, miR-146 and IL-17A confirm the data about the possible role of these miRNAs in regulating IL-17A production. The opposite changes of IL-17A and miR-223 systemic and local levels confirm the data about the possible role of miR-223 in regulating IL-17 function. Further analysis with larger sets is needed to confirm these results.References:[1]Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord. 2010; 11:209.[2]Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X. et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 2012; 7(10):e46082.[3]Schaefer J, Nakra N, Montufar-Solis D, Vigneswaran N, Klein J. Role for miR-223 and Roquin in IL-10 mediated regulation of IL-17. J Immunol. 2013; 190 (1 Supplement) 171.9.Acknowledgments:The study was supported by Grant 14-D/2012, Grant 60/2013 and Grant 61/2015 from Medical University-Sofia, BulgariaDisclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1116.2-1116
Author(s):  
Y. Ben Abderrazek ◽  
R. Dhahri ◽  
W. Lahmar ◽  
M. Slouma ◽  
B. Louzir ◽  
...  

Background:The role of rheumatoid arthritis as an ischemic heart disease and heart failure risk factor is well acknowledged even if the physiopathological pathways are still debated. The effect of anemia on myocardial deformation has already been established and a hemoglobin level below 9g/dL was associated with a significantly lower global longitudinal strain (GLS) patients with no history of CVD or chronic inflammatory diseases.[1]Objectives:In the present study, we looked into the effect of anemia and hemoglobin on the myocardial impairement in RA patients.Methods:We conducted a monocentric cross-sectional study between march 2019 and september 2019 on 36 RA patients without any history of cardiovascular disease and non-altered left ventricular ejection fraction in the outpatient population of the rheumatology department of the military hospital of Tunis matched with 36 healthy control subjects. Both groups underwent conventional echocardiography and STE to measure GLS; subclinical left ventricular systolic dysfunction was defined as a GLS > −18%, and a complete blood cell count; anemia was defined as Hemoglobin levels < 12 g/dL for women and < 13 g/dL for men.Results:Myocardial deformation study revealed that rheumatoid arthritis patients had a significantly worse GLS than healthy controls (18.99±2.81% vs 20.42±1.33%; P=.015). We also observed that third of the RA patients had subclinical left ventricular systolic dysfunction.In our report 36% of RA patients were anemic. In our univariate analysis anemia was found to be significantly correlated with GLS (r=−0.368, P=.027) and hemoglobin was found to be the best predictor of subclinical LVSD in our ROC curve analysis (AUC=0.752, 95% CI: 0.577-0.927, P=.02). In our multivariate analysis anemia was the only factor that was independently related to subclinical LVSD (OR: 11.39, 95% CI: 1.57-82.89, P=.016).Figure 1.ROC curve analysis for Hemoglobin as a predictor of subclinical left ventricular systolic dysfunctionConclusion:To our knowledge, this is the first study to look into the relationship between GLS and anemia among RA patients, and now it is safe to say that anemia is yet another added burden on the myocardial function in RA patients that needs to be taken into account when discussing therapeutic action.References:[1]Zhou Q, Shen J, Liu Y, Luo R, Tan B, Li G. Assessment of left ventricular systolic function in patients with iron deficiency anemia by three-dimensional speckle-tracking echocardiography. Anatol J Cardiol. 2017;18(3):194–9.Disclosure of Interests:None declared


2021 ◽  
Author(s):  
Yuanyuan Hu ◽  
Xuzhao Bian ◽  
Chao Wu ◽  
Yan Wang ◽  
Yang Wu ◽  
...  

Abstract Background: Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods: Blood plasma from five CP children and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of using hsa_circ_0086354 as a biomarker of CP.Results: 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change>2, p<0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of CP children and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate CP children and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, miR-4741 and miR-4656, and much literature evidence suggested that miR-181a may be a key target of hsa_circ_0086354 to regulate neuronal survival and neuronal differentiation. Conclusion: Hsa_circ_0086354 was significantly down-regulated in blood plasma of CP children, which may be a novel competent biomarker for early diagnosis of CP.


2020 ◽  
Author(s):  
Jinling Zhang ◽  
Hongyan Li ◽  
Liangjian Zhou ◽  
lianling Yu ◽  
Fengyuan Che ◽  
...  

Abstract Objective:The study aimed to propose a modified N stage of esophageal cancer (EC) on basis of based on the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously. Method:Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which derived from the comparison of the hezode rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.Results:The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. Cross-validation method within the cohort identified the predictive accuracy of this modified N stage, and ROC curve analysis demonstrated the superiority of this modified N stage over that of the AJCC.Conclusion:The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.


2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199492
Author(s):  
Ji-Yong Zhang ◽  
Hong Peng ◽  
Si-Tang Gong ◽  
Yong-Mei Zeng ◽  
Miao Huang ◽  
...  

Objective To investigate the relationship between peroxisome proliferator-activated receptor gamma (PPARγ) mRNA, serum adiponectin (ADP) and lipids in paediatric patients with Kawasaki disease (KD). Methods This prospective study enrolled paediatric patients with KD and grouped them according to the presence or absence of coronary artery lesions (CAL). A group of healthy age-matched children were recruited as the control group. The levels of PPARγ mRNA, serum ADP and lipids were compared between the groups. Receiver operating characteristic (ROC) curve analysis was undertaken to determine if the PPARγ mRNA level could be used as a predictive biomarker of CAL prognosis. Results The study enrolled 42 patients with KD (18 with CAL [CAL group] and 24 without CAL [NCAL group]) and 20 age-matched controls. PPARγ mRNA levels in patients with KD were significantly higher than those in the controls; but significantly lower in the CAL group than the NCAL group. ROC curve analysis demonstrated that the PPARγ mRNA level provided good predictive accuracy for the prognosis of CAL. There was no association between PPARγ, ADP and lipid levels. Conclusion There was dyslipidaemia in children with KD, but there was no correlation with PPARγ and ADP. PPARγ may be a predictor of CAL in patients with KD with good predictive accuracy.


2020 ◽  
Author(s):  
Marco Di Carlo ◽  
Marika Tardella ◽  
Emilio Filippucci ◽  
Marina Carotti ◽  
Fausto Salaffi

Abstract Background. In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. However, in patients with RA it is not yet clear how to interpret, in quantitative terms, the presence of B-lines, the LUS artifact indicative of ILD. The aim of this study was to determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods. A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Results. 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). The presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4.Conclusion. The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.


2021 ◽  
Author(s):  
Yuanyuan Hu ◽  
Xuzhao Bian ◽  
Chao Wu ◽  
Yan Wang ◽  
Yang Wu ◽  
...  

Abstract Background: Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods: Blood plasma from five CP children and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of using hsa_circ_0086354 as a biomarker of CP.Results: 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change>2, p<0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of CP children and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate CP children and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, miR-4741 and miR-4656, and much literature evidence suggested that miR-181a may be a key target of hsa_circ_0086354 to regulate neuronal survival and neuronal differentiation. Conclusion: Hsa_circ_0086354 was significantly down-regulated in blood plasma of CP children, which may be a novel competent biomarker for early diagnosis of CP.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
He Huang ◽  
Shilei Xu ◽  
Aidong Chen ◽  
Fen Li ◽  
Jiezhong Wu ◽  
...  

Background. Although accumulating evidence suggested that a molecular signature panel may be more effective for the prognosis prediction than routine clinical characteristics, current studies mainly focused on colorectal or colon cancers. No reports specifically focused on the signature panel for rectal cancers (RC). Our present study was aimed at developing a novel prognostic signature panel for RC. Methods. Sequencing (or microarray) data and clinicopathological details of patients with RC were retrieved from The Cancer Genome Atlas (TCGA-READ) or the Gene Expression Omnibus (GSE123390, GSE56699) database. A weighted gene coexpression network was used to identify RC-related modules. The least absolute shrinkage and selection operator analysis was performed to screen the prognostic signature panel. The prognostic performance of the risk score was evaluated by survival curve analyses. Functions of prognostic genes were predicted based on the interaction proteins and the correlation with tumor-infiltrating immune cells. The Human Protein Atlas (HPA) tool was utilized to validate the protein expression levels. Results. A total of 247 differentially expressed genes (DEGs) were commonly identified using TCGA and GSE123390 datasets. Brown and yellow modules (including 77 DEGs) were identified to be preserved for RC. Five DEGs (ASB2, GPR15, PRPH, RNASE7, and TCL1A) in these two modules constituted the optimal prognosis signature panel. Kaplan-Meier curve analysis showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that this risk score had high predictive accuracy for unfavorable prognosis, with the area under the ROC curve of 0.915 and 0.827 for TCGA and GSE56699 datasets, respectively. This five-mRNA classifier was an independent prognostic factor. Its predictive accuracy was also higher than all clinical factor models. A prognostic nomogram was developed by integrating the risk score and clinical factors, which showed the highest prognostic power. ASB2, PRPH, and GPR15/TCL1A were predicted to function by interacting with CASQ2/PDK4/EPHA67, PTN, and CXCL12, respectively. TCL1A and GPR15 influenced the infiltration levels of B cells and dendritic cells, while the expression of PRPH was positively associated with the abundance of macrophages. HPA analysis supported the downregulation of PRPH, RNASE7, CASQ2, EPHA6, and PDK4 in RC compared with normal controls. Conclusion. Our immune-related signature panel may be a promising prognostic indicator for RC.


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