LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway

BackgroundThe study of the immune microenvironment in prostate cancer (PRAD) has brought new opportunities for the current traditional treatment regimens. Therefore, our goal is to develop a universal immunodiagnostic marker to improve patient survival.MethodsBioinformatics analysis: We collected 59...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qi Zhao, Yingying Cheng, Ying Xiong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	prostate cancer (PRAD) tumor-infiltrated immune cells (TIICs) lactoferrin (LTF) granulocyte-macrophage colony-stimulating factor (GM-CSF) JAK/STAT3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4342ee917db24710a53e3b0453d0de37
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4342ee917db24710a53e3b0453d0de37
record_format	dspace
spelling	oai:doaj.org-article:4342ee917db24710a53e3b0453d0de372021-11-17T11:00:39ZLTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway2234-943X10.3389/fonc.2021.692117https://doaj.org/article/4342ee917db24710a53e3b0453d0de372021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.692117/fullhttps://doaj.org/toc/2234-943XBackgroundThe study of the immune microenvironment in prostate cancer (PRAD) has brought new opportunities for the current traditional treatment regimens. Therefore, our goal is to develop a universal immunodiagnostic marker to improve patient survival.MethodsBioinformatics analysis: We collected 591 samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts and evaluated the abundance and distribution of immune cell members in the PRAD expression profile matrix in the mixed cell population by CIBERSORT, ESTIMATE, single-sample gene set enrichment analysis (ssGSEA), and other methods. The target genes related to PRAD immune microenvironment and tumor mutation load were obtained by overlap analysis and verified by pan-cancer analysis. Cell experiment: The cell transfection scheme was designed, and the experiment was divided into three groups: overexpressing lactoferrin (LTF) group, empty plasmid group, and control group. After obtaining cells in each group, the gene and protein expression levels of LTF and signal transduction of signal transducer and activator of transcription 3 (STAT3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the above three groups were detected by real-time PCR and Western blot, respectively. Finally, the level of GM-CSF secretion in the three groups was detected by ELISA.ResultsMacrophages, resting mast cells, and plasma cells play an important role in PRAD immune microenvironment. In addition, high tumor mutation load [tumor mutational burden (TMB)] was positively correlated with lymph node metastasis in patients with PRAD. As the core gene of the PRAD immune microenvironment, the low expression of LTF in PRAD promotes the occurrence of immunodeficiency, PRAD, and the enrichment of the Janus kinase (JAK)/STAT3 signal pathway. Through cell experiments, it was found that the content of LTF mRNA and protein increased significantly, while the content of STAT3 and GM-CSF mRNA and protein decreased significantly in the overexpressed LTF group. The level of GM-CSF in the supernatant of cell culture was significantly decreased in the overexpression group of LTF.ConclusionThe core gene we proposed is one of the most promising biomarkers to improve the overall survival rate of PRAD and provides an important theoretical basis for the study of the mechanism of the LTF-mediated JAK/STAT3 pathway in PRAD.Qi ZhaoYingying ChengYing XiongFrontiers Media S.A.articleprostate cancer (PRAD)tumor-infiltrated immune cells (TIICs)lactoferrin (LTF)granulocyte-macrophage colony-stimulating factor (GM-CSF)JAK/STAT3Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer (PRAD) tumor-infiltrated immune cells (TIICs) lactoferrin (LTF) granulocyte-macrophage colony-stimulating factor (GM-CSF) JAK/STAT3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	prostate cancer (PRAD) tumor-infiltrated immune cells (TIICs) lactoferrin (LTF) granulocyte-macrophage colony-stimulating factor (GM-CSF) JAK/STAT3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Qi Zhao Yingying Cheng Ying Xiong LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway
description	BackgroundThe study of the immune microenvironment in prostate cancer (PRAD) has brought new opportunities for the current traditional treatment regimens. Therefore, our goal is to develop a universal immunodiagnostic marker to improve patient survival.MethodsBioinformatics analysis: We collected 591 samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts and evaluated the abundance and distribution of immune cell members in the PRAD expression profile matrix in the mixed cell population by CIBERSORT, ESTIMATE, single-sample gene set enrichment analysis (ssGSEA), and other methods. The target genes related to PRAD immune microenvironment and tumor mutation load were obtained by overlap analysis and verified by pan-cancer analysis. Cell experiment: The cell transfection scheme was designed, and the experiment was divided into three groups: overexpressing lactoferrin (LTF) group, empty plasmid group, and control group. After obtaining cells in each group, the gene and protein expression levels of LTF and signal transduction of signal transducer and activator of transcription 3 (STAT3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the above three groups were detected by real-time PCR and Western blot, respectively. Finally, the level of GM-CSF secretion in the three groups was detected by ELISA.ResultsMacrophages, resting mast cells, and plasma cells play an important role in PRAD immune microenvironment. In addition, high tumor mutation load [tumor mutational burden (TMB)] was positively correlated with lymph node metastasis in patients with PRAD. As the core gene of the PRAD immune microenvironment, the low expression of LTF in PRAD promotes the occurrence of immunodeficiency, PRAD, and the enrichment of the Janus kinase (JAK)/STAT3 signal pathway. Through cell experiments, it was found that the content of LTF mRNA and protein increased significantly, while the content of STAT3 and GM-CSF mRNA and protein decreased significantly in the overexpressed LTF group. The level of GM-CSF in the supernatant of cell culture was significantly decreased in the overexpression group of LTF.ConclusionThe core gene we proposed is one of the most promising biomarkers to improve the overall survival rate of PRAD and provides an important theoretical basis for the study of the mechanism of the LTF-mediated JAK/STAT3 pathway in PRAD.
format	article
author	Qi Zhao Yingying Cheng Ying Xiong
author_facet	Qi Zhao Yingying Cheng Ying Xiong
author_sort	Qi Zhao
title	LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway
title_short	LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway
title_full	LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway
title_fullStr	LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway
title_full_unstemmed	LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway
title_sort	ltf regulates the immune microenvironment of prostate cancer through jak/stat3 pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4342ee917db24710a53e3b0453d0de37
work_keys_str_mv	AT qizhao ltfregulatestheimmunemicroenvironmentofprostatecancerthroughjakstat3pathway AT yingyingcheng ltfregulatestheimmunemicroenvironmentofprostatecancerthroughjakstat3pathway AT yingxiong ltfregulatestheimmunemicroenvironmentofprostatecancerthroughjakstat3pathway
_version_	1718425606479151104

LTF Regulates the Immune Microenvironment of Prostate Cancer Through JAK/STAT3 Pathway

Ejemplares similares