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

Abstract

Background: Tumor metastasis is the main cause of death of cancer patients, and the existence of cancer stem cells is the basis of tumor metastasis. However, the systematic analysis of the stemness of prostate cancer cells is still not abundant. This article explores the effective factors that lead to the stemness of prostate cancer cells with multi-omics data mining.Methods: Gene expression modules that were strongly related to the stemness of prostate cancer cells were obtained with WGCNA and stemness scores, based on the prostate cancer transcriptome data in TCGA. Calculated the copy number variation of stemness genes of prostate cancer and evaluated the difference of transcription factors in prostate cancer and normal tissues, based on CNV (copy number variation) data and ATAC-seq data. The protein interaction network of stemness genes of prostate cancer was constructed with the STRING database. At the same time, the correlation between stemness genes of prostate cancer and immune cells was analyzed.Results: Prostate cancer with high Gleason grade was more stemness. The gene set highly related to prostate cancer stemness had higher CNV in prostate cancer samples than normal samples. The transcription factors of stemness genes had similar expressions but had different contributions in normal and prostate cancer tissues. And particular transcription factors enhanced the stemness of prostate cancer, such as PUM1, CLOCK, SP1, TCF12, and so on. The lower tumor immune microenvironment was conducive to the stemness of prostate cancer, and CD8+ T cells and M1 macrophages might play an important role than other immune cells in the tumor microenvironment. We also found that EZH2 played a central role in stemness genes and was negatively correlated with resting mast cells and positively correlated with activated memory CD4+ T cells.Conclusions: This study found that high copy number variation, specific transcription factors, and low immune microenvironment contributed to the stemness of prostate cancer cells through systematic multi-omics analysis. These findings would provide new clues and directions for future research of prostate cancer stem cells.

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“…It is widely accepted that replication stress plays a key role in initiating anti-tumor immunity by inducing cancerrelated neoantigens (31, 32), and its absence is intensively correlated with the immune desert phenotype. Consequently, the low immunity and high level of CNV can jointly contribute to strong cancer stemness (33), accounting for the result that patients of CS3 were tolerant of many ATR and week1 inhibitors in our study.…”

Identification of Hub Genes for Controlling Cancer Stem Cell Characteristics in Colorectal Cancer by Bioinformatics Analysis

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Identification of the Key Serum Biomarkers to Diagnose and Predict Metastasis of Osteosarcoma Based on the Analysis of Immune Cell Infiltration Characteristics

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