J Cancer 2021; 12(4):1249-1257. doi:10.7150/jca.49409 This issue

Research Paper

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

Xiao-Dan Lin1*, Ning Lin1*, Ting-Ting Lin1*, Yu-Peng Wu1, Peng Huang1, Zhi-Bin Ke1, Yun-Zhi Lin1, Shao-Hao Chen1, Qing-Shui Zheng1, Yong Wei1, Xue-Yi Xue1, Rong-Jin Lin2✉, Ning Xu1✉

1. Department of Urology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
2. Department of Nursing, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
*These authors contributed equally to this work.

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Citation:
Lin XD, Lin N, Lin TT, Wu YP, Huang P, Ke ZB, Lin YZ, Chen SH, Zheng QS, Wei Y, Xue XY, Lin RJ, Xu N. Identification of marker genes and cell subtypes in castration-resistant prostate cancer cells. J Cancer 2021; 12(4):1249-1257. doi:10.7150/jca.49409. Available from https://www.jcancer.org/v12p1249.htm

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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.

Keywords: single-cell RNA-seq, castration-resistant prostate cancer cells, marker genes, cell subtypes