Abstract
Bladder carcinoma (BLCA) is a highly heterogeneous disease, and the underlying biological behavior is still poorly understood. Here, single-cell RNA sequencing was performed on four clinical samples of different grades from three patients, and 26,792 cell transcriptomes were obtained revealing different tumor ecosystems. We found that N-glycan biosynthesis pathway was activated in high-grade tumor, but TNF-related pathway was activated in cystitis glandularis. The tumor microenvironment (TME) of different samples showed great heterogeneity. Notably, cystitis glandularis was dominated by T cells, low-grade and high-grade tumors by macrophages, while TME in patient with high-grade relapse by stromal cells. Our research provides single-cell transcriptome profiles of cystitis glandularis and BLCA in different clinical states, and the biological program revealed by single-cell data can be used as biomarkers related to clinical prognosis in independent cohorts.
Highlights
Cystitis glandularis (CG) usually occurs in chronic inflammation, with epithelial hyperplasia and metaplasia
It is worth noting that a small number of epithelial cells from CG have been inferred to be malignant epithelium, indicating that copy number variation (CNV) are present in normal epithelial cells in an inflammatory state
We performed single-cell RNA sequencing of CG, LG, HG, and its recurring bladder samples, producing the single-cell transcriptome data that allowed us to describe the biological characteristics of different clinical state samples
Summary
Cystitis glandularis (CG) usually occurs in chronic inflammation, with epithelial hyperplasia and metaplasia. It is widely believed that cystitis glandularis is a benign lesion, patients with intestinal metaplasia and urinary tract accumulation are still at risk of developing bladder cancer [2]. Bladder cancer is the most common malignant tumor of the urinary system, and urothelial cancer is the most common pathological type. NMIBC papillary lesions are divided into urothelial papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), lowgrade (LG) papillary urothelial carcinoma, and high-grade (HG) papillary urothelial carcinoma [5]. The mechanism of the development of BLCA is not clear, and whether CG is a precancerous lesion is controversial. It is necessary to conduct an in-depth discussion on the occurrence and development mechanism of BLCA and the relationship between BLCA and CG from the cellular levels
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