Research Papers:

Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder

Xiaolong Zhang, Meng Zhang, Yong Hou, Liqin Xu, Weidong Li, Zhihui Zou, Chunxiao Liu, Abai Xu and Song Wu _

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Oncotarget. 2016; 7:66069-66076. https://doi.org/10.18632/oncotarget.11803

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Xiaolong Zhang1,2,3,*, Meng Zhang1,2,3,4,*, Yong Hou5, Liqin Xu5, Weidong Li1, Zhihui Zou6, Chunxiao Liu6, Abai Xu6, Song Wu1,2,3

1Department of Urological Surgery, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, China

2Shenzhen Following Precision Medical Institute, Shenzhen Luohu Hospital Group, Shenzhen, China

3Shenzhen Gene Detection Public Service Platform of Clinical Application, Shenzhen Luohu Hospital Group, Shenzhen, China

4Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

5BGI-Shenzhen, Shenzhen, China

6Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Song Wu, email: [email protected]

Keywords: bladder cancer, squamous cell carcinoma, single-cell transcriptome sequencing, gene expression

Received: March 24, 2016    Accepted: August 10, 2016    Published: September 01, 2016


Cell-to-cell expression heterogeneity within a single tumor is a common phenotype among various cancer types including squamous cell carcinoma. To further study the fundamentals and importance of heterogeneity of cell functions and its potential mechanisms, we performed single-cell RNA-seq (scRNA-seq) on human squamous cell carcinoma of the bladder (SCCB) and its corresponding physiologically normal epithelia. Extensive differentially expressed genes were uncovered by comparing cancer and normal single cells, which were preferentially enriched in cancer-correlated pathways, such as p53 signaling and bladder cancer pathway. Furthermore, the most diversely expressed genes were particularly enriched in MAPK signaling pathway, such as CACNG4, CACNA1E and CACNA1H, which involve in cancer evolution and heterogeneity formation. Co-expression network and hub-gene analyses revealed several remarkable “hub genes” of each regulatory module. Some of them are cancer related, such as POU2F3, NKD1 and CYP2C8, while LINC00189, GCC2 and OR9Q1 genes are rarely reported in human diseases. The genes within an interesting module are highly correlated with others, which could be treated as potential targets for SCCB patients. Our findings have fundamental implications for SCCB biology and therapeutic strategies.

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