A prognostic immune predictor, HLA-DRA, plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

Piao, Xuan‐Mei; Kang, Ho Won; Jeong, Pildu; Byun, Young Joon; Lee, Hee Youn; Kim, Kyeong Ja; Seo, Soonjoo; Kim, Dong-Won; Lee, Jong‐Young; Ha, Yun‐Sok; Choi, Yung Hyun; Moon, Sung‐Kwon; Yun, Seok Joong; Kim, Wun-Jae

doi:10.1016/j.urolonc.2020.11.017

Cited by 13 publications

(8 citation statements)

References 27 publications

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“…HLA-DRA is reported to be a reliable biomarker for KIRC, which may play an important role in immunotherapy and improve prognosis (45). High expression of HLA-DRA is considered to be an immune factor that predicts prognosis and plays an immunomodulatory role in non-muscular and muscular-invasive bladder cancer (46). This is the first time we have provided evidence that HLA-DRA is highly expressed in PTC and related to infiltration level of activated dendritic cells.…”

Section: Discussionmentioning

confidence: 74%

“…Further study of its mechanism may provide a new target for PTC immunotherapy. Integrin beta2 (ITGB2), a subunit of integrin, accelerates leukocyte adhesion to endothelial cells, resulting in extravasation (46). ITGB2 regulates metabolic switch in cancer-associated fibroblasts through mitochondrial oxidative phosphorylation of NADH to promote oral squamous cell carcinoma proliferation (47).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer

Zhang

et al. 2022

Front. Endocrinol.

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BackgroundA growing body of evidence suggests that immune cell infiltration in cancer is closely related to clinical outcomes. However, there is still a lack of research on papillary thyroid cancer (PTC).MethodsBased on single-sample gene set enrichment analysis (SSGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) tool, the infiltration level of immune cell and key modules and genes associated with the level of immune cell infiltration were identified using PTC gene expression data from The Cancer Genome Atlas (TCGA) database. In addition, the co-expression network and protein-protein interactions network analysis were used to identify the hub genes. Moreover, the immunological and clinical characteristics of these hub genes were verified in TCGA and GSE35570 datasets and quantitative real-time polymerase chain reaction (PCR). Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of hub genes.ResultsActivated B cell, activated dendritic cell, CD56bright natural killer cell, CD56dim natural killer cell, Eosinophil, Gamma delta T cell, Immature dendritic cell, Macrophage, Mast cell, Monocyte, Natural killer cell, Neutrophil and Type 17 T helper cell were significantly changed between PTC and adjacent normal groups. WGCNA results showed that the black model had the highest correlation with the infiltration level of activated dendritic cells. We found 14 hub genes whose expression correlated to the infiltration level of activated dendritic cells in both TCGA and GSE35570 datasets. After validation in the TCGA dataset, the expression level of only 5 genes (C1QA, HCK, HLA-DRA, ITGB2 and TYROBP) in 14 hub genes were differentially expressed between PTC and adjacent normal groups. Meanwhile, the expression levels of these 5 hub genes were successfully validated in GSE35570 dataset. Quantitative real-time PCR results showed the expression of these 4 hub genes (except C1QA) was consistent with the results in TCGA and GSE35570 dataset. Finally, these 4 hub genes had diagnostic value to distinguish PTC and adjacent normal controls.ConclusionsHCK, HLA-DRA, ITGB2 and TYROBP may be key diagnostic biomarkers and immunotherapy targets in PTC.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer

Zhang

et al. 2022

Front. Endocrinol.

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“…HLA-DRA is an HLA class II alpha chain paralog that plays a vital role in the immune system and responses by presenting peptides. HLA-DRA is highly expressed in bladder cancer tissues than corresponding adjacent tissues and indicates poor progression-free survival (49). In kidney renal clear cell carcinoma, HLA-DRA serves as a reliable biomarker and may play a vital role in cancer immunotherapy (50).…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Related to Immune Infiltration in the Tumor Microenvironment of Cutaneous Melanoma

et al. 2021

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Cutaneous melanoma (CM) is the leading cause of skin cancer deaths and is typically diagnosed at an advanced stage, resulting in a poor prognosis. The tumor microenvironment (TME) plays a significant role in tumorigenesis and CM progression, but the dynamic regulation of immune and stromal components is not yet fully understood. In the present study, we quantified the ratio between immune and stromal components and the proportion of tumor-infiltrating immune cells (TICs), based on the ESTIMATE and CIBERSORT computational methods, in 471 cases of skin CM (SKCM) obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were analyzed by univariate Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis to identify prognosis-related genes. The developed prognosis model contains ten genes, which are all vital for patient prognosis. The areas under the curve (AUC) values for the developed prognostic model at 1, 3, 5, and 10 years were 0.832, 0.831, 0.880, and 0.857 in the training dataset, respectively. The GSE54467 dataset was used as a validation set to determine the predictive ability of the prognostic signature. Protein–protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were used to verify “real” hub genes closely related to the TME. These hub genes were verified for differential expression by immunohistochemistry (IHC) analyses. In conclusion, this study might provide potential diagnostic and prognostic biomarkers for CM.

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“…Furthermore, HLA DRB1*03 was also found in T-LGLL (T cell large granular lymphocyte leukemia), less common in responders to therapy [32]. Elevated HLA DRA expression was recently described in IBM [33], and HLA-DRA is a prognostic immune predictor in bladder cancer [34]. In IBM, the chemokine receptor CCR5 gene variants have also been found [4,33].…”

Section: Genetic Susceptibility For Ibm and Tumorsmentioning

confidence: 99%

Inclusion Body Myositis and Neoplasia: A Narrative Review

Damian

Solomon

et al. 2022

IJMS

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Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.

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A prognostic immune predictor, HLA-DRA, plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

Cited by 13 publications

References 27 publications

Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer

Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer

Identification of Genes Related to Immune Infiltration in the Tumor Microenvironment of Cutaneous Melanoma

Inclusion Body Myositis and Neoplasia: A Narrative Review

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