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Comprehensive analysis of PILRΑ's association with the prognosis, tumor immune infiltration, and immunotherapy in pan-cancer.

ABSTRACT: Paired immunoglobulin-like type 2 receptor alpha (PILRA) plays a vital role in regulating broad immune responses. However, the roles of PILRA in cancer immunity remain unexplored yet. In the current study, we comprehensively analyzed the oncogenic and immunologic roles of PILRA at a pan-cancer level based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PILRA was significantly dysregulated and frequently mutated in pan-cancer. Its expression and mutation status significantly impacted patient prognosis in several cancers. Besides, PILRA expression was positively correlated with ESTIMATE scores and the abundances of tumor-infiltrating immune cells. Concurrently, PILRA expression was significantly associated with predictive biomarkers of cancer immunotherapy, and positively correlated with the prognostic outcomes of cancer patients receiving immunotherapy. Mechanistically, enrichment analysis implied that PILRA might be involved in the regulation of immune response and metabolic process. This study uncovered the immunological roles of PILRA in cancers and its potential as a novel biomarker and therapeutic target for cancer immunotherapy.

SUBMITTER: Li Q

PROVIDER: S-EPMC10471747 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Comprehensive analysis of PILRΑ's association with the prognosis, tumor immune infiltration, and immunotherapy in pan-cancer.

Li Qiao Q Yang Zhirong Z He Xiaoyan X Yang Xin X

Scientific reports 20230831 1

Paired immunoglobulin-like type 2 receptor alpha (PILRA) plays a vital role in regulating broad immune responses. However, the roles of PILRA in cancer immunity remain unexplored yet. In the current study, we comprehensively analyzed the oncogenic and immunologic roles of PILRA at a pan-cancer level based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PILRA was significantly dysregulated and frequently mutated in pan-cancer. Its expression and mutation status significantly impa ...[more]

PMID: 37652967

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Project description:BackgroundNew immunotherapeutic strategies based on predictors are urgently needed. Toll-like receptor adaptor interacting with SLC15A4 on the lysosome (TASL) was recently confirmed to fulfill an important role in the innate immune response. However, whether TASL is involved in tumor development and immunotherapy response prediction has not been reported.MethodsTCGA and GTEx were used to yield transcriptional, genetic, and epigenetic levels of TASL in 33 cancer types. CIBERSORT was used to explore the correlation between TASL expression and multiple immune-related signatures and tumor-infiltrating immune cell content in different cancer types. The ability of TASL to predict tumor immunotherapy response was analyzed in seven datasets. Finally, we tested TASL expression in human glioma cell lines and tissue samples and analyzed its correlation with clinicopathological parameters.ResultsTASL is widely heterogeneous at the transcriptional, genetic, and epigenetic levels. High TASL expression is an independent poor prognostic factor for immune "cold" tumor Low-Grade Glioma (LGG) but an opposite factor for "hot" tumors Lung Adenocarcinoma (LUAD) and Skin Cutaneous Melanoma (SKCM). TASL may affect tumor immune infiltration by mediating tumor-infiltrating lymphocytes and tumor-associated macrophages. It may differentially affect the prognosis of the three cancers by regulating the immunosuppressive microenvironment in LGG and the immunostimulatory microenvironment in LUAD and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in cancers such as SKCM and was also experimentally confirmed to be positively associated with adverse clinicopathological features of gliomas.ConclusionTASL expression is an independent prognostic factor for LGG, LUAD, and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in certain cancer types such as SKCM. Further basic studies focusing on TASL expression and tumor immunotherapy are urgently needed.

Project description:BackgroundCD73 is adenosine generation molecule, which is involved in the immune regulation. However, the roles of CD73 in the tumor microenvironment remain unknown.MethodsCD73 expression levels in pan-cancers were analyzed, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein ALTAS (HPA) databases. Kaplan-Meier (KM) plotter was used to analyze the prognostic values of CD73. Immune scores in pan-cancers was evaluated by ESTIMATE. TIMER2.0 and UCSCXena were used to explore the correlation between CD73 and immune infiltration/immune checkpoints/tumor mutation burden (TMB)/microsatellite instability (MSI). CD73 expression correlated genes in tumor tissues were screened by using LinkedOmics tool.ResultsFirstly, CD73 was significant increased in following cancer types: esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), brain lower grade glioma (LGG), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD) and stomach adenocarcinoma (STAD). Secondly, high CD73 expression was associated with poor overall survival in patients with breast invasive carcinoma (BRCA), CESC, HNSC, liver hepatocellular carcinoma (LIHC), LUAD, lung squamous cell carcinoma (LUSC), PAAD and STAD. However, in KIRC and UCEC, patients high CD73 expression showed a favorable prognosis. Thirdly, the immune scores of the high CD73 expression in bladder urothelial carcinoma (BLCA), BRCA, kidney chromophobe (KICH), LUAD, LUSC, ovarian serous cystadenocarcinoma (OV), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and skin cutaneous melanoma (SKCM) were significant higher than that of patients with low CD73 expression. Furthermore, we observed a positive correlation between CD73 and the multiple immune cells infiltration, including CD4+ memory T cells, CD8+ T cells, Treg cells, myeloid DC and macrophage, particularly in BRCA and LUAD. There was no strong correlation between CD73 and TMB/MSI. In LUAD, CD73 expression correlated genes were mainly enrichment in positive regulation of cell proliferation, cell adhesion, positive regulation of kinase activity, cellular response to LPS. However, in UCEC, CD73 correlated genes were mainly associated with fatty acid omega-oxidation, protein localization to endoplasmic reticulum exit site, endoplasmic reticulum to Golgi vesicle-mediated transport.ConclusionCD73 could be used to predict the prognosis of patients with several cancers. The potential functional mechanism of CD73 involved in cancer progress may not only dependent on its immunomodulatory effects.

Project description:ObjectivesLaminin subunit alpha 3 (LAMA3) has been implicated in various cellular processes relevant to cancer progression, including cell proliferation, migration, and adhesion. In this study, we explored the expression, prognostic significance, and functional role of LAMA3 across multiple cancer types.MethodologyThe in silico analyses involve using various bioinformatics tools and databases, such as The Cancer Genome Atlas (TCGA), TIMER2.0, GEPIA2, UALCAN, Kaplan-Meier (KM) plotter, GENT2, Human Protein Atlas (HPA), OncoDB, Gene Set Cancer Analysis (GSCA), and TISIDB. The in vitro analyses include cell culture, gene knockdown, and assays for cell proliferation, colony formation, and wound healing.ResultsPan-cancer analysis revealed significant variations in LAMA3 expression, with upregulation observed in cancers such as pancreatic adenocarcinoma (PAAD) and stomach adenocarcinoma (STAD), and downregulation in breast cancer (BRCA) and colon adenocarcinoma (COAD). Prognostic analyses indicated high LAMA3 expression correlated with poor overall survival (OS) in PAAD and STAD, whereas low expression was associated with adverse outcomes in BRCA. Validation analysis confirmed differential expression and localized LAMA3 primarily to the endoplasmic reticulum. Analysis of clinical features in BRCA, PAAD, and STAD showed consistent expression trends across different stages, races, and age groups. Additionally, mutational and copy number variations (CNVs) analyses revealed prevalent heterozygous amplifications and deletions in LAMA3 across BRCA, PAAD, and STAD. Promoter methylation was inversely correlated with LAMA3 expression in BRCA, PAAD, and STAD, although survival outcomes were unaffected. Protein-protein interaction (PPI) and gene enrichment analyses indicated LAMA3's involvement in ECM-receptor interactions and PI3K-Akt signaling, pathways critical in cancer. Finally, functional assays following LAMA3 knockdown in HT-29 cells demonstrated reduced cell proliferation, colony formation, and wound healing, implicating LAMA3 in tumor growth and metastasis.ConclusionOverall, these findings suggest that LAMA3 plays a multifaceted role in tumorigenesis and holds potential as a prognostic biomarker and therapeutic target in multiple cancers.

Dataset Information

Comprehensive analysis of PILRΑ's association with the prognosis, tumor immune infiltration, and immunotherapy in pan-cancer.

Publications

Comprehensive analysis of PILRΑ's association with the prognosis, tumor immune infiltration, and immunotherapy in pan-cancer.

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