scholarly journals lncRNA PCAT14 Is a Diagnostic Marker for Prostate Cancer and Is Associated with Immune Cell Infiltration

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yunkun Yan ◽  
Jianjun Liu ◽  
Zhijian Xu ◽  
Mushi Ye ◽  
Jianchang Li

Objective. To investigate the relationship between the long noncoding RNA (lncRNA) Prostate cancer-associated transcription factors 14 (PCAT14) and the clinical characteristics of prostate cancer and immune cell infiltration. Methods. The relationship between PCAT14 expression and the clinicopathological characteristics of prostate cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic (ROC) curves were used to evaluate the value of PCAT14 as a diagnostic marker for prostate cancer. The relationship between PCAT14 and immune cell infiltration was analyzed to explore the effect of PCAT14 on the immune-related functions of prostate cancer. Results. The ROC curve showed that PCAT14 had a significant diagnostic ability ( area   under   curve = 0.818 ) for prostate cancer. A reduced expression of PCAT14 in prostate cancer was related to T stage, N stage, primary therapy outcome, residual tumor, Gleason score, and age. The expression of PCAT14 was independently associated with the progression-free interval in prostate cancer patients. The infiltration of immune cells in prostate cancer showed a significant negative correlation between the expression of PCAT14 and plasmacytoid dendritic cells, activated dendritic cells, regulatory T cells, and neutrophils. Conclusions. PCAT14 is highly expressed in prostate cancer and is expected to be a diagnostic marker. PCAT14 might promote the development of prostate cancer through chemokines, antimicrobials, and cytokines that affect the infiltration of immune cells.

2020 ◽  
Author(s):  
Jukun Song ◽  
Song He ◽  
Wei Wang ◽  
Jiaming Su ◽  
Dongbo Yuan ◽  
...  

Abstract Background Immune infiltration of Prostate cancer (PCa) was highly related to clinical outcomes. However, previous works failed to elucidate the diversity of different immune cell types that make up the function of the immune response system. The aim of the study was to uncover the composition of TIICs in PCa utilizing the CIBERSORT algorithm and further reveal the molecular characteristics of PCa subtypes. Method In the present work, we employed the CIBERSORT method to evaluate the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We analyzed the correlation between immune cell infiltration and clinical information. The tumor-infiltrating immune cells of the TCGA PCa cohort were analyzed for the first time. The fractions of 22 immune cell types were imputed to determine the correlation between each immune cell subpopulation and clinical feature. Three types of molecular classification were identified via R-package of “CancerSubtypes”. The functional enrichment was analyzed in each subtype. The submap and TIDE algorithm were used to predict the clinical response to immune checkpoint blockade, and GDSC was employed to screen chemotherapeutic targets for the potential treatment of PCa. Results In current work, we utilized the CIBERSORT algorithm to assess the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We investigated the correlation between immune cell infiltration and clinical data. The tumor-infiltrating immune cells in the TCGA PCa cohort were analyzed. The 22 immune cells were also calculated to determine the correlation between each immune cell subpopulation and survival and response to chemotherapy. Three types of molecular classification were identified. Each subtype has specific molecular and clinical characteristics. Meanwhile, Cluster I is defined as advanced PCa, and is more likely to respond to immunotherapy. Conclusions Our results demonstrated that differences in immune response may be important drivers of PCa progression and response to treatment. The deconvolution algorithm of gene expression microarray data by CIBERSOFT provides useful information about the immune cell composition of PCa patients. In addition, we have found a subtype of immunopositive PCa subtype and will help to explore the reasons for the poor effect of PCa on immunotherapy, and it is expected that immunotherapy will be used to guide the individualized management and treatment of PCa patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shaokun Wang ◽  
Li Pang ◽  
Zuolong Liu ◽  
Xiangwei Meng

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.


2021 ◽  
Author(s):  
Meng Wang ◽  
Ruijie Zhang ◽  
Qiongfeng Guan ◽  
Yindan Yao ◽  
Liyuan Han

Abstract Background: This study aimed to identify potential diagnostic markers of ischemic stroke (IS) and discuss the function of immune cell infiltration during the pathological process. Methods: We used IS datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified, and functional correlation analysis was performed. We then screened and verified the diagnostic markers of IS. We evaluated the infiltration of immune cells in infarcts using CIBERSORT and analyzed the correlation between diagnostic markers and infiltrating immune cells. Results: A total of 366 DEGs were screened in this study. Genes encoding CTSG, F13A1, PABPC1, ECHDC2, BIRC2 and infiltrating monocytes, M0 macrophages, activated dendritic cells, and neutrophils (area under the curve [AUC] = 0.945) were identified as diagnostic markers of IS. Immune cell infiltration analysis suggested that memory B cells, regulatory T cells, M0 macrophages, CD8 + T cells, γδT cells, activated natural killer cells, monocytes, activated mast cells, and neutrophils were involved in the IS process. Analysis of correlations between expressed genes and infiltrating immune cells found that CTSG was positively associated with M0 macrophages, F13A1 was positively associated with monocytes, PABPC1 was positively associated with activated dendritic cells, eosinophils were negatively associated with neutrophils, ECHDC2 was negatively associated with monocytes, and BIRC2 was positively associated with eosinophils. Conclusion: five genes and four types of immune cells were identified as diagnostic markers of IS, and immune cell infiltration may play an important role in the progression of IS.


2021 ◽  
Vol 11 ◽  
Author(s):  
Young-Sil An ◽  
Se-Hyuk Kim ◽  
Tae Hoon Roh ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  

BackgroundThe purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions.MethodsThis retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions.ResultsThe degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68.ConclusionsIn metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.


2021 ◽  
Author(s):  
Xiaoyan Li ◽  
Jing Zhou ◽  
Jie He

Abstract Background: Sarcoidosis (SA) is an immune disorder disease featured with granulomas formation. The work purposed to uncover potential markers for sarcoidosis (SA) diagnosis and explore how immune cell infiltration contributes to the pathogenesis of SA.Methods: Sarcoidosis GSE83456 samples and GSE42834 from Gene Expression Omnibus (GEO) were analyzed as the training and external validation sets, respectively. R statistical software was employed to uncover the differentially expressed genes (DEGs) of GSE83456. SVM algorithms and LASSO logistic regression were applied for screening and verification of the diagnostic markers for key module genes. The infiltration of immune cells in sarcoidosis patients’ blood samples was assessed by CIBERSORT. The expression of serum BATF2 and PDK4 was detected by RT-qPCR method, and the value of BATF2 and PDK4 mRNA expression in the diagnosis of pulmonary sarcoidosis was analyzed.Results: In total, 580 DEGs were identified from the key module. PDK4 (AUC=0.942) and BATF4 (AUC=0.980) were revealed as diagnostic markers of sarcoidosis. We found that monocytes, T cells regulatory (Tregs), mast cells, macrophages,NK cells, and dendritic cells may contribute to sarcoidosis development. In addition, PDK4 and BATF4 were closely associated with these immune cells. BATF2 and PDK4 were highly expressed in pulmonary sarcoidosis. BATF2 and PDK4 combined to predict the area under the ROC curve of pulmonary sarcoidosis was 0.922.Conclusions: PDK4 and BATF4 could be used as diagnostic markers of sarcoidosis, and immune cell infiltration severs an important role in sarcoidosis.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 46-46
Author(s):  
Sophie Earle ◽  
Toru Aoyama ◽  
Alexander I. Wright ◽  
Darren Treanor ◽  
Yohei Miyagi ◽  
...  

46 Background: Since the ACTS-GC trial, Japanese patients with stage II/III gastric cancer (GC) receive adjuvant S1 chemotherapy. However, selection of patients (pts) by TNM stage does not predict benefit from adjuvant S1 with certainty. Thus, there is an urgent clinical need to identify predictive biomarkers. Increasing evidence suggests tumor immune cell infiltration may be related to GC pts prognosis. We tested the hypothesis that extent and type of immune cell infiltration in GC is related to benefit from adjuvant chemotherapy. Methods: Tissue microarrays from 252 GC resections (109 pts treated by surgery alone (S), 143 pts treated by surgery and adjuvant S1 chemotherapy (SC)) from the Kanagawa Cancer Center Hospital (Yokohama, Japan) were investigated by immunohistochemistry for common leucocytes antigen (CD45), neutrophils (CD66b), macrophages (CD68 and CD163), T-cell subtypes (CD45R0, CD8, CD3), B-cells (CD20) and Treg cells (FOXP3). Staining was quantified as percentage immunoreactivity/area by automated image analysis. Relationship with overall survival was analyzed. A Cox regression model was used to identify independent prognostic markers and treatment interaction effect. Results: The hazard ratio of S1 was 0.694 in this GC cohort which is similar to the results of the ACTS-GC trial. CD45 and CD45R0 were independent prognostic markers in the S group only (CD45 p=0.032, CD45R0 p=0.003). A treatment interaction effect was seen for CD45, CD45R0, and CD68 (p value for test of interaction: CD45 p=0.062, CD45R0 p=0.082, CD68 p=0.057). Survival in the SC group was significantly poorer compared to the S group for CD45>56% or CD68>7% (p<0.05). Conclusions: This is the first study to investigate the relationship between tumor immune cell infiltration at time of surgery and benefit from adjuvant chemotherapy. Our results indicate that GC patients with high intratumoral levels of CD68, CD45, or CD45R0 positive immune cells might not benefit from adjuvant S1 chemotherapy. These findings require validation in a second independent dataset before conducting a prospective study stratifying patients with stage II/III GC based upon extent of CD45, CD45R0, or CD68 immune cell infiltration for adjuvant treatment.


2014 ◽  
Vol 297 (5) ◽  
pp. 925-938 ◽  
Author(s):  
Lauren J. Howson ◽  
Katrina M. Morris ◽  
Takumi Kobayashi ◽  
Cesar Tovar ◽  
Alexandre Kreiss ◽  
...  

2021 ◽  
Author(s):  
Xiaofen Pan ◽  
Xingkui Tang ◽  
Minling Liu ◽  
Xijun Luo ◽  
Mengyuan Zhu ◽  
...  

Abstract BackgroundTumor microenvironment consists of tumor cells, immune cells and other matric components. Tumor infiltration immune cells are associated with prognosis. But all the current prognosis evaluation system dose not take tumor immune cells other matrix component into consideration. In the current study, we aimed to construct a prognosis predictive model based on tumor microenvironment.MethodCIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. Immune cell infiltration (ICI) scores of each patient were determine by principal-component analysis. Patients were divided to high and low ICI score groups. Survival, gene expression and somatic mutation of the two groups were compared.ResultsPatients with no lymph node invasion, no metastasis, T1-2 disease and stage I-II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and WNT signaling pathway were enriched in high ICI score group. Immune-checkpoint genes and immune-activity associated genes were significantly decreased in high ICI score. Patients in high ICI score group had better survival than low ICI score group. Prognostic value of ICI score was independent of TMB.ConclusionICI score might serve as an independent prognostic biomarker in colon cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yimin Pan ◽  
Kai Xiao ◽  
Yue Li ◽  
Yuzhe Li ◽  
Qing Liu

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m6A) methylation modification reportedly plays roles in immune response. The relationship between the m6A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m6A modification pattern and m6A-related signatures based on 21 regulators. Thereafter, the m6A methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients’ clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse m6A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m6A-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 m6A regulators and specific immune cell infiltration was demonstrated in our study and the m6A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m6A methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to m6A-related signatures.


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