scholarly journals Development and Validation of an Immune Microenvironment Based Prognostic Signature and Signal Pathways in Prostate Cancer

2020 ◽  
Author(s):  
Qi Zhao ◽  
Yingying Cheng ◽  
Yujie Ren ◽  
Xianfa Li ◽  
Ying Xiong
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Target Gene ◽  
Core Gene ◽  
Signal Pathways ◽  
Primary Immune Deficiency ◽  
Prognostic Signature ◽  
Immune Microenvironment ◽  
Gm Csf ◽  
Stat Pathway

Abstract Background: The study of the PCa immune microenvironment has brought new opportunities for the clinical diagnosis and treatment of PCa, but the current study has failed to obtain satisfactory results. We aim to develop a generalized, individualized immune prognostic signature that can improve the survival rate of patients.Methods: We collected a total of 591 sample data from the TCGA and GEO cohorts, and evaluated the abundance and distribution of immune cell members in the mixed cell population in the gene expression matrix by CIBERSORT, ESTIMATE, ssGSEA, and other methods. Calculate the TMB value of the mutant gene to evaluate the reliability of PCa for immunotherapy. Besides, the genes related to the immune microenvironment and mutation load of PCa are obtained, and the target genes are obtained by the intersection with the immune-related genes in the ImmPort database. And perform pan-cancer analysis of the target gene to evaluate the immunological commonality and biological pathways in a variety of cancers. Finally, a Western blot experiment was used to explore the mechanism of the target gene in PCa immune microenvironment.Results: We found that M0, M2, and Mast cell sresting differed significantly between prostate cancer and normal tissue and that patients with low plasma cell abundance were more likely to develop lymph node metastasis. LTF, as a core gene, is closely related to changes in the immune microenvironment of PCa, and its low expression in tumors promotes primary immune deficiency, cancer development, and enrichment in the JAK/STAT signaling pathway. Cell experiments found that LTF overexpression reduces tumor-derived GM-CSF secretion by inhibiting JAK/STAT pathway, achieving the purpose of regulating tumor immune microenvironment and inhibiting PCa cell proliferation and migration.Conclusions: The proposed clinical-immune signature and core gene is the most promising biomarkers for improving the overall survival rate of PCa. It has been verified that overexpression of LTF reduces the secretion of tumor-derived GM-CSF by inhibiting the JAK/STAT pathway.

scholarly journals Development and Validation of an Immune Microenvironment Based Prognostic Signature and Signal Pathways in Prostate Cancer

2020 ◽  
Author(s):  
Qi Zhao ◽  
Yingying Cheng ◽  
Yujie Ren ◽  
Xianfa Li ◽  
Ying Xiong
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Target Gene ◽  
Core Gene ◽  
Signal Pathways ◽  
Primary Immune Deficiency ◽  
Prognostic Signature ◽  
Immune Microenvironment ◽  
Gm Csf ◽  
Stat Pathway

Abstract BackgroundThe study of the PCa immune microenvironment has brought new opportunities for the clinical diagnosis and treatment of PCa, but the current study has failed to obtain satisfactory results. We aim to develop a generalized, individualized immune prognostic signature that can improve the survival rate of patients.MethodsWe collected a total of 591 sample data from the TCGA and GEO cohorts, and evaluated the abundance and distribution of immune cell members in the mixed cell population in the gene expression matrix by CIBERSORT, ESTIMATE, ssGSEA, and other methods. Calculate the TMB value of the mutant gene to evaluate the reliability of PCa for immunotherapy. Besides, the genes related to the immune microenvironment and mutation load of PCa are obtained, and the target genes are obtained by the intersection with the immune-related genes in the ImmPort database. And perform pan-cancer analysis of the target gene to evaluate the immunological commonality and biological pathways in a variety of cancers. Finally, a Western blot experiment was used to explore the mechanism of the target gene in PCa immune microenvironment.ResultsWe found that M0, M2, and Mast cell sresting differed significantly between prostate cancer and normal tissue and that patients with low plasma cell abundance were more likely to develop lymph node metastasis. LTF, as a core gene, is closely related to changes in the immune microenvironment of PCa, and its low expression in tumors promotes primary immune deficiency, cancer development, and enrichment in the JAK/STAT signaling pathway. Cell experiments found that LTF overexpression reduces tumor-derived GM-CSF secretion by inhibiting JAK/STAT pathway, achieving the purpose of regulating tumor immune microenvironment and inhibiting PCa cell proliferation and migration.ConclusionsThe proposed clinical-immune signature and core gene is the most promising biomarkers for improving the overall survival rate of PCa. It has been verified that overexpression of LTF reduces the secretion of tumor-derived GM-CSF by inhibiting the JAK/STAT pathway.

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Zhao ◽  
Yingying Cheng ◽  
Ying Xiong
Keyword(s):  
Prostate Cancer ◽  
Core Gene ◽  
Janus Kinase ◽  
Gene Set Enrichment Analysis ◽  
Mutation Load ◽  
Immune Microenvironment ◽  
Stat3 Pathway ◽  
Gm Csf ◽  
The Core ◽  
Gene And Protein Expression

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.

790: Ten-Year Disease Free Survival Rate Calculated with PSA Cutpoint 0.2 NG/ML in Men After Brachytherapy for T1C Prostate Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 209-209
Author(s):  
James B. Benton ◽  
Frank A. Critz ◽  
W. Hamilton Williams ◽  
Clinton T. Holladay ◽  
Philip D. Shrake
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free Survival Rate ◽  
Disease Free

scholarly journals High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zao Dai ◽  
Ping Liu
Keyword(s):  
Prostate Cancer ◽  
Transcription Factors ◽  
Copy Number Variation ◽  
Cancer Cells ◽  
Immune Cells ◽  
Copy Number ◽  
Tumor Metastasis ◽  
Prostate Cancer Cells ◽  
Immune Microenvironment ◽  
Number Variation

Abstract Background Tumor metastasis is the main cause of death of cancer patients, and cancer stem cells (CSCs) is the basis of tumor metastasis. However, systematic analysis of the stemness of prostate cancer cells is still not abundant. In this study, we explore the effective factors related to the stemness of prostate cancer cells by comprehensively mining the multi-omics data from TCGA database. Methods Based on the prostate cancer transcriptome data in TCGA, gene expression modules that strongly relate to the stemness of prostate cancer cells are obtained with WGCNA and stemness scores. Copy number variation of stemness genes of prostate cancer is calculated and the difference of transcription factors between prostate cancer and normal tissues is evaluated by using CNV (copy number variation) data and ATAC-seq data. The protein interaction network of stemness genes in prostate cancer is constructed using the STRING database. Meanwhile, the correlation between stemness genes of prostate cancer and immune cells is analyzed. Results Prostate cancer with higher Gleason grade possesses higher cell stemness. The gene set highly related to prostate cancer stemness has higher CNV in prostate cancer samples than that in normal samples. Although the transcription factors of stemness genes have similar expressions, they have different contributions between normal and prostate cancer tissues; and particular transcription factors enhance the stemness of prostate cancer, such as PUM1, CLOCK, SP1, TCF12, and so on. In addition, the lower tumor immune microenvironment is conducive to the stemness of prostate cancer. CD8 + T cells and M1 macrophages may play more important role in the stemness of prostate cancer than other immune cells in the tumor microenvironment. Finally, EZH2 is found to play a central role in stemness genes and is negatively correlated with resting mast cells and positively correlated with activated memory CD4 + T cells. Conclusions Based on the systematic and combined analysis of multi-omics data, we find that high copy number variation, specific transcription factors, and low immune microenvironment jointly contribute to the stemness of prostate cancer cells. These findings may provide us new clues and directions for the future research on stemness of prostate cancer.

Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression

2002 ◽  
Vol 88 (2) ◽  
pp. 363-371 ◽  
Author(s):  
Aruna V. Krishnan ◽  
Donna M. Peehl ◽  
David Feldman
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Vitamin D ◽  
Target Gene ◽  
Cancer Growth ◽  
Target Gene Expression

scholarly journals Identification ofTDRD1as a direct target gene ofERGin primary prostate cancer

2013 ◽  
Vol 133 (2) ◽  
pp. 335-345 ◽  
Author(s):  
Joost L. Boormans ◽  
Hanneke Korsten ◽  
Angelique J.C. Ziel-van der Made ◽  
Geert J.L.H. van Leenders ◽  
Carola V. de Vos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Target Gene ◽  
Primary Prostate Cancer ◽  
Direct Target Gene ◽  
Direct Target

TM4SF1 , a novel primary androgen receptor target gene over-expressed in human prostate cancer and involved in cell migration

The Prostate ◽  
2011 ◽  
Vol 71 (11) ◽  
pp. 1239-1250 ◽  
Author(s):  
Nathalie Allioli ◽  
Séverine Vincent ◽  
Virginie Vlaeminck-Guillem ◽  
Myriam Decaussin-Petrucci ◽  
Florence Ragage ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Androgen Receptor ◽  
Target Gene ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Androgen Receptor Target Gene

In vitro p53 and/or Rb antisense oligonucleotide treatment in association with growth factors induces the proliferation of peripheral hematopoietic progenitors

1995 ◽  
Vol 108 (3) ◽  
pp. 1287-1293
Author(s):  
T. Mahdi ◽  
A. Brizard ◽  
C. Millet ◽  
P. Dore ◽  
J. Tanzer ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Types ◽  
Suppressor Gene ◽  
Antisense Oligodeoxynucleotide ◽  
Signal Pathways ◽  
Semisolid Medium ◽  
Gm Csf ◽  
Colony Forming Units ◽  
Macrophage Colony

In this work we intended to determine whether p53 and/or retinoblastoma (Rb) tumor suppressor genes are involved at specific stages in the process of in vitro human peripheral stem cell hematopoiesis. Mononuclear peripheral blood cells were depleted of adherent cells and T lymphocytes (A-T-PMCs). Cells were then cultured in semisolid medium, under conditions that favor the growth of specific progenitor cell types. A-T-PMCs were exposed to p53 and/or Rb sense, scrambled DNA and antisense oligodeoxynucleotides. p53 and/or Rb antisenses (but not their senses or scrambled DNA) treatment of A-T-PMCs resulted in a significantly increase in the number of granulocyte/macrophage colony-forming units (CFU-GM) in the presence of interleukin-3 (IL-3) and/or granulocyte/macrophage colony-stimulating factor (GM-CSF). After antisense treatment, blast forming units/erythroblasts (BFU-E) derived from A-T-PMCs cultured in the presence of IL-3 + erythropoietin (Epo) were also increased whereas colony forming units/erythroblasts (CFU-E) were not markedly affected in the presence of Epo only. Megakaryocytic colony (CFU-Meg) formation from A-T-PMCs in the presence of interleukin-6 (IL-6) + IL-3 + Epo was also increased after antisense oligodeoxynucleotide treatment. These results are consistent with the hypothesis that p53 and Rb tumor suppressor gene products are involved in the control of distinct signal pathways in different peripheral progenitor cells.

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