Identification of marker genes and cell subtypes in castration-resistant prostate cancer cells

Abstract

The diverse tumor cell populations may be the critical roles in relapse and resistance to treatment in prostate cancer patients. This study aimed to identify new marker genes and cell subtypes among castration-resistant prostate cancer (CRPC) cells. We downloaded single-cell RNA seq profiles (GSE67980) from the Gene Expression Omnibus (GEO) database. Principal component (PC) analysis and t-Distributed Stochastic Neighbor Embedding (TSNE) analysis were performed to identify marker genes. CRPC cells were clustered and annotated. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses among marker genes were performed. A total of 1500 genes with larger standardized variance were obtained. The top 20 genes were demonstrated in each identified 20 PCs. PC with P-value < 0.05 was selected, including PC1, PC7, PC8, and PC14. The TSNE analysis classified cells as two clusters. The top 6 genes in cluster 0 included HBB, CCL5, SLITRK4, GZMB, BBIP1, and PF4V1. Plus, the top 6 genes in cluster 1 included MLEC, CCT8, CCT3, EPCAM, TMPRSS2, EIF4G2. The GO analysis revealed that these marker genes were mainly enriched in RNA catabolic process, translational initiation, mitochondrial inner membrane, cytosolic part, ribosome, cell adhesion molecule binding, cadherin binding, and structural constituent of ribosome. The KEGG analysis showed that these marker genes mainly enriched in metabolism associated pathways, including carbon metabolism, cysteine and methionine metabolism, propanoate metabolism, pyruvate metabolism, and citrate cycle pathways. To conclude, our results provide essential insights into the spectrum of cellular heterogeneity within human CRPC cells. These marker genes, GO terms and pathways may be critical in the development and progression of human CRPC.

Combined DNA Methylation and Transcriptomic Assessments to Determine a Prognostic Model for PD-1-Negative Hepatocellular Carcinoma

“…Interestingly, several DMEGs (e.g., TBX15 , REG1A , and HBB ) were found in all three regions, indicating that these genes may have transcriptional differences caused by differential methylation. Previous reports have shown that TBX15 expression can be used as a prognostic marker for HCC ( Morine et al, 2020 ), and HBB has been reported to play a key role in prostate cancer differentiation and in a variety of important biological pathways (e.g., iron metabolism) ( Chen and Sun, 2021 ; Lin et al, 2021 ). Based on the present expression data, we identified four different regulatory gene sets in the three DNA regions, for a total of 31 DMEGs ( Figure 4E ).…”

Exploring the role of differentially expressed metabolic genes and their mechanisms in bone metastatic prostate cancer

“…According to a related study, HBB may be a novel tumour suppressor gene in anaplastic thyroid cancer (ATC) ( Onda et al, 2005 ). PCa was found to have high HBB variations, and it was also considered a potential prognostic biomarker ( Davalieva et al, 2017 ; Lin et al, 2021 ). And high HBB expression may promote neutrophils infiltration.…”

Epigenetic and Epitranscriptomic Control in Prostate Cancer

“…Using TCGA methylation and RNA-seq data, Xu et al performed an epigenetic integrative analysis between normal and PCa tissue, in order to detect the pathways in which DNA methylation-driven genes were significantly enriched [ 35 ]. More recently, in the study by Lin et al, using single-cell RNA-seq profiles, the authors identified new signature genes and cell subtypes among CRPC cells [ 36 ]. All this evidence brings out a clear role for epigenetic regulation in PCa control.…”