scholarly journals Immune Cell as a Promising Biomarker in the Diagnosis and Prognosis of Cutaneous Melanoma by Using Machine Learning

Author(s):  
Jing Tang ◽  
Hongqaun Ye ◽  
Wan qi

Abstract Background: Tumor infiltration, is known to associate with various cancer initiations and progressions, is potential therapeutic target for this aggressive skin cancer.Methods: single sample gene set enrichment analysis (ssGSEA) algorithm was applied to assess the relative expression of 24 types of immune cell from public database. Firstly, the differentially expressed immune cells between melanomas and normal samples were identified. Next, multiple machine learning algorithms were performed to evaluate the efficiency of immune cells in diagnosis of melanoma. In addition, the feature selection in machine learning methods was used to figure out the most important prognostic immune cells for developing biomarker to predict the prognosis of melanoma.Results: In comparison with the expression of immune cells in tumors and normal controls, we built the immune diagnostic models in training dataset, which can accurately classify melanoma patients from normal (LR AUC= 0.965, RF AUC= 0.99, SVM AUC=0.963, LASSO AUC= 0.964 and NNET AUC=0.989). These diagnostic models also validated in three outside datasets and suggested over 90% sensitivity and specificity to distinguish melanomas from normal patients. Moreover, we also developed a robust immune cell biomarker which could estimate the prognosis of melanoma. This biomarker also further validated in internal and external datasets. Next, we constructed nomogram combined risk score of biomarker and clinical characteristics, which showed good accuracies in predicting 3 and 5 years’ survival. The decision curve of nomogram model manifested a higher net benefit than tumor stage. In addition, melanoma patients divided into high and low risk subgroups by applied risk score system. The high risk group have a significantly shorter survival time than the low risk subgroup. Gene Set Enrichment Analysis (GSEA) analysis revealed that complement, epithelial mesenchymal transition and inflammatory response and so on significantly activated in high risk group. Conclusions: We constructed immune cell related diagnostic and prognostic models, which could provide new clinical applications for diagnosing and predicting the survival of melanoma patients.

2021 ◽  
Author(s):  
Yanjia Hu ◽  
Jing Zhang ◽  
Jing Chen

Abstract Background Hypoxia-related long non-coding RNAs (lncRNAs) have been proven to play a role in multiple cancers and can serve as prognostic markers. Lower-grade gliomas (LGGs) are characterized by large heterogeneity. Methods This study aimed to construct a hypoxia-related lncRNA signature for predicting the prognosis of LGG patients. Transcriptome and clinical data of LGG patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). LGG cohort in TCGA was chosen as training set and LGG cohorts in CGGA served as validation sets. A prognostic signature consisting of fourteen hypoxia-related lncRNAs was constructed using univariate and LASSO Cox regression. A risk score formula involving the fourteen lncRNAs was developed to calculate the risk score and patients were classified into high- and low-risk groups based on cutoff. Kaplan-Meier survival analysis was used to compare the survival between two groups. Cox regression analysis was used to determine whether risk score was an independent prognostic factor. A nomogram was then constructed based on independent prognostic factors and assessed by C-index and calibration plot. Gene set enrichment analysis and immune cell infiltration analysis were performed to uncover further mechanisms of this lncRNA signature. Results LGG patients with high risk had poorer prognosis than those with low risk in both training and validation sets. Recipient operating characteristic curves showed good performance of the prognostic signature. Univariate and multivariate Cox regression confirmed that the established lncRNA signature was an independent prognostic factor. C-index and calibration plots showed good predictive performance of nomogram. Gene set enrichment analysis showed that genes in the high-risk group were enriched in apoptosis, cell adhesion, pathways in cancer, hypoxia etc. Immune cells were higher in high-risk group. Conclusion The present study showed the value of the 14-lncRNA signature in predicting survival of LGGs and these 14 lncRNAs could be further investigated to reveal more mechanisms involved in gliomas.


2021 ◽  
Author(s):  
Yong Lv ◽  
ShuGuang Jin ◽  
Bo Xiang

Abstract BackgroundTreatment of neuroblastoma is evolving toward precision medicine. LncRNAs can be used as prognostic biomarkers in many types of cancer.MethodsBased on the RNA-seq data from GSE49710, we built a lncRNAs-based risk score using the least absolute shrinkage and selection operation (LASSO) regression. Cox regression, receiver operating characteristic curves were used to evaluate the association of the LASSO risk score with overall survival. Nomograms were created and then validated in an external cohort from TARGET database. Gene set enrichment analysis was performed to identify the significantly changed biological pathways. ResultsThe 16-lncRNAs-based LASSO risk score was used to separate patients into high-risk and low-risk groups. In GSE49710 cohort, the high-risk group exhibited a poorer OS than those in the low-risk group (P<0.001). Moreover, multivariate Cox regression analysis demonstrated that LASSO risk score was an independent risk factor (HR=6.201;95%CI:2.536-15.16). The similar prognostic powers of the 16-lncRNAs were also achieved in the external cohort and in stratified analysis. In addition, a nomogram was established and worked well both in the internal validation cohort (C-index=0.831) and external validation cohort (C-index=0.773). The calibration plot indicated the good clinical utility of the nomogram. Gene set enrichment analysis (GSEA) indicated that high-risk group was related with cancer recurrence, metastasis and inflammatory associated pathways.ConclusionThe lncRNA-based LASSO risk score is a promising and potential prognostic tool in predicting the survival of patients with neuroblastoma. The nomogram combined the lncRNAs and clinical parameters allows for accurate risk assessment in guiding clinical management.


Author(s):  
Mei Chen ◽  
Zhenyu Nie ◽  
Yan Li ◽  
Yuanhui Gao ◽  
Xiaohong Wen ◽  
...  

Background: Ferroptosis is closely related to the occurrence and development of cancer. An increasing number of studies have induced ferroptosis as a treatment strategy for cancer. However, the predictive value of ferroptosis-related lncRNAs in bladder cancer (BC) still need to be further elucidated. The purpose of this study was to construct a predictive signature based on ferroptosis-related long noncoding RNAs (lncRNAs) to predict the prognosis of BC patients.Methods: We downloaded RNA-seq data and the corresponding clinical and prognostic data from The Cancer Genome Atlas (TCGA) database and performed univariate and multivariate Cox regression analyses to obtain ferroptosis-related lncRNAs to construct a predictive signature. The Kaplan-Meier method was used to analyze the overall survival (OS) rate of the high-risk and low-risk groups. Gene set enrichment analysis (GSEA) was performed to explore the functional differences between the high- and low-risk groups. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the predictive signature and immune status. Finally, the correlation between the predictive signature and the treatment response of BC patients was analyzed.Results: We constructed a signature composed of nine ferroptosis-related lncRNAs (AL031775.1, AL162586.1, AC034236.2, LINC01004, OCIAD1-AS1, AL136084.3, AP003352.1, Z84484.1, AC022150.2). Compared with the low-risk group, the high-risk group had a worse prognosis. The ferroptosis-related lncRNA signature could independently predict the prognosis of patients with BC. Compared with clinicopathological variables, the ferroptosis-related lncRNA signature has a higher diagnostic efficiency, and the area under the receiver operating characteristic curve was 0.707. When patients were stratified according to different clinicopathological variables, the OS of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the high-risk group. ssGSEA showed that the predictive signature was significantly related to the immune status of BC patients. High-risk patients were more sensitive to anti-PD-1/L1 immunotherapy and the conventional chemotherapy drugs sunitinib, paclitaxel, cisplatin, and docetaxel.Conclusion: The predictive signature can independently predict the prognosis of BC patients, provides a basis for the mechanism of ferroptosis-related lncRNAs in BC and provides clinical treatment guidance for patients with BC.


2021 ◽  
Author(s):  
Zhian Ling ◽  
Yuting Liang ◽  
Suping Wei ◽  
Yuanming Chen ◽  
Jinmin Zhao

Abstract Background N6-methylandenosine (m6A) methylation is one of the most common methylation modifications in RNA. At present, a large number of studies have found that m6A methylation can regulate the occurrence and development of tumors by modifying mRNA. However, it is still unclear how m6A modifies Long non-coding RNA (lncRNA) that regulates mRNA expression by interacting with miRNA to affect the occurrence and development of osteosarcoma(OS). Therefore, exploring the lncRNAs related to m6A methylation and identifying lncRNAs that have both prognostic effects and immune functions are things that need to be solved urgently. Methods The published gene expression data of OS and complete clinical annotation files were obtained from the TARGET database. LncRNAs with P <0.001 from the results of Pearson correlation coefficient analysis as m6A-related lncRNAs were screened. Single-factor Cox regression analysis was used to screening prognostic- related lncRNA combined with the clinical information of patients and constructed a prognostic model based on lasso regression analysis. Then we explored the differences in survival and immune function of different subtypes that be obtained using the Consensus Cluster. The enrichment of differential genes between high and low risk groups in the KEGG pathway is achieved through Gene set enrichment analysis(GSEA). Results We obtained 706 lncRNAs in the TARGET database. Consensus clustering method were used to divide patients with OS into subgroups based on the expression of 26 prognostic-related lncRNAs. Through Kaplan-Meier survival analysis, there are significant differences between the two subgroups. The average immune score (P = 0.02), stromal score(P =0.027), and estimate score༈P = 0.015༉were higher in cluster 1 than in cluster 2. We found that compared with cluster 2, SIGLEC15, HAVCR2, LAG3, and PDCD1 were highly expressed in cluster 1.We obtain a prognostic model by lasso regression analysis. In the training group and the text group, the OS curve showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. In the training set, univariate Cox regression analysis and multivariate Cox regression analysis showed that the risk score was correlated with the prognosis of OS patients. In the high-risk group, the Linoleic acid metabolism and the Glycine, serine and threonine metabolism pathway were mainly involved by Gene Set Enrichment analysis. The abundance of Mast cells activated (P ≦0.024) and T cells CD4 (P ≦0.0044) naive were positively association the risk score. Conclusions This study clarified the important role of m6A-related lncRNAs in the prognosis and immune microenvironment of patients with OS, and indicate that m6A-related prognostic lncRNA signals may provide new targets for the diagnosis and treatment of OS.


2021 ◽  
Author(s):  
Chuan-Qi Xu ◽  
Kui-Sheng Yang ◽  
Shu-Xian Zhao ◽  
Jian Lv

Abstract Objective: Pancreatic cancer (PC) is one of the most malignant tumors. Cytosolic DNA sensing have been found to play an essential role in tumor. In this study, a cytosolic DNA sensing-related genes (CDSRGs) signature was constructed and the potential mechanisms also been discussed.Methods: The RNA expression and clinical data of PC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Subsequently, univariate (UCR) and multivariate Cox regression (MCR) analyses were conducted to establish a prognostic model in the TCGA patients, which was verified by GEO patients. Cancer immune infiltrates were investigated via single sample gene set enrichment analysis (ssGSEA) and Tumor Immune Estimation Resource (TIMER). Finally, Gene Set Enrichment Analysis (GSEA) was used to investigate the related signaling pathways.Results: A prognostic model comprising four genes (POLR2E,IL18, MAVS, and FADD) was established. The survival rate of patients in the low-risk group was significantly higher than that of patients in the high-risk group. In addition, CDSRGs-risk score was proved as an independent prognostic factor in PC. Immune infiltrates and drug sensitivity are associated with POLR2E,IL18, MAVS, and FADD expression.Conclusions: In summary, we present and validated a CDSRGs risk model that is an independent prognostic factor and indicates the immune characteristics of PC. This prognostic model may facilitate the personalized treatment and monitoring.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Shen ◽  
Li-rong Xu ◽  
Xiao Tang ◽  
Chang-po Lin ◽  
Dong Yan ◽  
...  

Abstract Background Atherosclerosis is a chronic inflammatory disease that affects multiple arteries. Numerous studies have shown the inherent immune diversity in atheromatous plaques and suggest that the dysfunction of different immune cells plays an important role in atherosclerosis. However, few comprehensive bioinformatics analyses have investigated the potential coordinators that might orchestrate different immune cells to exacerbate atherosclerosis. Methods Immune infiltration of 69 atheromatous plaques from different arterial beds in GSE100927 were explored by single-sample-gene-set enrichment analysis (presented as ssGSEA scores), ESTIMATE algorithm (presented as immune scores) and CIBERSORT algorithm (presented as relative fractions of 22 types of immune cells) to divide these plaques into ImmuneScoreL cluster (of low immune infiltration) and ImmuneScoreH cluster (of high immune infiltration). Subsequently, comprehensive bioinformatics analyses including differentially-expressed-genes (DEGs) analysis, protein–protein interaction networks analysis, hub genes analysis, Gene-Ontology-terms and KEGG pathway enrichment analysis, gene set enrichment analysis, analysis of expression profiles of immune-related genes, correlation analysis between DEGs and hub genes and immune cells were conducted. GSE28829 was analysed to cross-validate the results in GSE100927. Results Immune-related pathways, including interferon-related pathways and PD-1 signalling, were highly enriched in the ImmuneScoreH cluster. HLA-related (except for HLA-DRB6) and immune checkpoint genes (IDO1, PDCD-1, CD274(PD-L1), CD47), RORC, IFNGR1, STAT1 and JAK2 were upregulated in the ImmuneScoreH cluster, whereas FTO, CRY1, RORB, and PER1 were downregulated. Atheromatous plaques in the ImmuneScoreH cluster had higher proportions of M0 macrophages and gamma delta T cells but lower proportions of plasma cells and monocytes (p < 0.05). CAPG, CECR1, IL18, IGSF6, FBP1, HLA-DPA1 and MMP7 were commonly related to these immune cells. In addition, the advanced-stage carotid plaques in GSE28829 exhibited higher immune infiltration than early-stage carotid plaques. Conclusions Atheromatous plaques with higher immune scores were likely at a more clinically advanced stage. The progression of atherosclerosis might be related to CAPG, IGSF6, IL18, CECR1, FBP1, MMP7, FTO, CRY1, RORB, RORC, PER1, HLA-DPA1 and immune-related pathways (IFN-γ pathway and PD-1 signalling pathway). These genes and pathways might play important roles in regulating immune cells such as M0 macrophages, gamma delta T cells, plasma cells and monocytes and might serve as potential therapeutic targets for atherosclerosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ang Wang ◽  
Siru Nie ◽  
Zhi Lv ◽  
Jing Wen ◽  
Yuan Yuan

Gastric mucosal immune microenvironment plays an important role in the occurrence and development of diseases such as inflammation and cancer. In the present study, single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of cytokines and the degree of immune cell infiltration in four different gastric mucosa tissues from normal gastric mucosa, simple gastritis, and atrophic gastritis to gastric cancer. Here, we show the immune microenvironments of these four gastric mucosae were significantly different. From inflammation to gastric cancer, most immunoinflammatory cells showed a downward trend such as central memory CD4 T cell. Instead, several cells showed an upward trend such as macrophage. Additionally, we found some chemokines/interleukins were illustrated to be low expressed (or highly expressed) in precancerous stage and highly expressed (or low expressed) in postcancerous stage, which demonstrated an opposite expression characteristic in pre-/postcancerous stage.


2021 ◽  
Vol 18 (6) ◽  
pp. 7743-7758
Author(s):  
Linlin Tan ◽  
◽  
Dingzhuo Cheng ◽  
Jianbo Wen ◽  
Kefeng Huang ◽  
...  

<abstract> <sec><title>Background</title><p>Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer.</p> </sec> <sec><title>Methods</title><p>The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures.</p> </sec> <sec><title>Results</title><p>We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups.</p> </sec> <sec><title>Conclusions</title><p>Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.</p> </sec> </abstract>


2021 ◽  
Vol 12 ◽  
Author(s):  
Facai Zhang ◽  
Xiaoming Wang ◽  
Yunjin Bai ◽  
Huan Hu ◽  
Yubo Yang ◽  
...  

ObjectivesThis study aimed to develop and validate a hypoxia signature for predicting survival outcomes in patients with bladder cancer.MethodsWe downloaded the RNA sequence and the clinicopathologic data of the patients with bladder cancer from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository?facetTab=files) and the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) databases. Hypoxia genes were retrieved from the Molecular Signatures Database (https://www.gsea-msigdb.org/gsea/msigdb/index.jsp). Differentially expressed hypoxia-related genes were screened by univariate Cox regression analysis and Lasso regression analysis. Then, the selected genes constituted the hypoxia signature and were included in multivariate Cox regression to generate the risk scores. After that, we evaluate the predictive performance of this signature by multiple receiver operating characteristic (ROC) curves. The CIBERSORT tool was applied to investigate the relationship between the hypoxia signature and the immune cell infiltration, and the maftool was used to summarize and analyze the mutational data. Gene-set enrichment analysis (GSEA) was used to investigate the related signaling pathways of differentially expressed genes in both risk groups. Furthermore, we developed a model and presented it with a nomogram to predict survival outcomes in patients with bladder cancer.ResultsEight genes (AKAP12, ALDOB, CASP6, DTNA, HS3ST1, JUN, KDELR3, and STC1) were included in the hypoxia signature. The patients with higher risk scores showed worse overall survival time than the ones with lower risk scores in the training set (TCGA) and two external validation sets (GSE13507 and GSE32548). Immune infiltration analysis showed that two types of immune cells (M0 and M1 macrophages) had a significant infiltration in the high-risk group. Tumor mutation burden (TMB) analysis showed that the risk scores between the wild types and the mutation types of TP53, MUC16, RB1, and FGFR3 were significantly different. Gene-Set Enrichment Analysis (GSEA) showed that immune or cancer-associated pathways belonged to the high-risk groups and metabolism-related signal pathways were enriched into the low-risk group. Finally, we constructed a predictive model with risk score, age, and stage and validated its performance in GEO datasets.ConclusionWe successfully constructed and validated a novel hypoxia signature in bladder cancer, which could accurately predict patients’ prognosis.


2021 ◽  
Vol 19 (1) ◽  
pp. 169-190
Author(s):  
Peiyuan Li ◽  
◽  
Gangjie Qiao ◽  
Jian Lu ◽  
Wenbin Ji ◽  
...  

<abstract> <p>Plasmacytoma variant translocation 1 (PVT1) is involved in multiple signaling pathways and plays an important regulatory role in a variety of malignant tumors. However, its role in the prognosis and immune invasion of bladder urothelial carcinoma (BLCA) remains unclear. This study investigated the expression of PVT1 in tumor tissue and its relationship with immune invasion, and determined its prognostic role in patients with BLCA. Patients were identified from the cancer genome atlas (TCGA). The enrichment pathway and function of PVT1 were explained by gene ontology (GO) term analysis, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA), and the degree of immune cell infiltration was quantified. Kaplan–Meier analysis and Cox regression were used to analyze the correlation between PVT1 and survival rate. PVT1-high BLCA patients had a lower 10-year disease-specific survival (DSS P &lt; 0.05) and overall survival (OS P &lt; 0.05). Multivariate Cox regression analysis showed that PVT1 (high vs. low) (P = 0.004) was an independent prognostic factor. A nomogram was used to predict the effect of PVT1 on the prognosis. PVT1 plays an important role in the progression and prognosis of BLCA and can be used as a medium biomarker to predict survival after cystectomy.</p> </abstract>


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