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Oncotarget. 2016 Oct 4;7(40):66069-66076. doi: 10.18632/oncotarget.11803.

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

Zhang X1,2,3, Zhang M1,2,3,4, Hou Y5, Xu L5, Li W1, Zou Z6, Liu C6, Xu A6, Wu S1,2,3.

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Department of Urological Surgery, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, China.
Shenzhen Following Precision Medical Institute, Shenzhen Luohu Hospital Group, Shenzhen, China.
Shenzhen Gene Detection Public Service Platform of Clinical Application, Shenzhen Luohu Hospital Group, Shenzhen, China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
BGI-Shenzhen, Shenzhen, China.
Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.


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.


bladder cancer; gene expression; single-cell transcriptome sequencing; squamous cell carcinoma

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