Alternative polyadenylation of single cells delineates cell types and serves as a prognostic marker in early stage breast cancer

• Published in: PloS one Vol. 14; no. 5; p. e0217196
• Main Authors: Kim, Nayoung, Chung, Woosung, Eum, Hye Hyeon, Lee, Hae-Ock, Park, Woong-Yang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.05.2019; Public Library of Science (PLoS)
• Subjects: 3' Untranslated regions; 3' Untranslated Regions - genetics; Algorithms; Analysis; B cells; Biology; Biology and Life Sciences; Biomarkers, Tumor - analysis; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Cancer cells; Cancer research; Carcinoma; Cell adhesion & migration; Cell Proliferation; Data collection; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene sequencing; Genes; Genetic aspects; Genomes; Glioblastoma; Glioblastomas; Gliomas; Health aspects; Health sciences; Humans; Immunology; Influence; Kidney cancer; Kidney Neoplasms - diagnosis; Kidney Neoplasms - genetics; Localization; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Myeloid cells; Overexpression; Physiological aspects; Polyadenylation; Prognosis; Renal cell carcinoma; Research and analysis methods; RNA; RNA sequencing; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Analysis, RNA; Single-Cell Analysis - methods; Stromal cells; T cells; Transcription; Tumor cells; Tumor Microenvironment; Tumors; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0217196

Alternative polyadenylation (APA) in 3' untranslated regions (3' UTR) plays an important role in regulating transcript abundance, localization, and interaction with microRNAs. Length-variation of 3'UTRs by APA contributes to efficient proliferation of cancer cells. In this study, we investigated APA in single cancer cells and tumor microenvironment cells to understand the physiological implication of APA in different cell types. We analyzed APA patterns and the expression level of genes from the 515 single-cell RNA sequencing (scRNA-seq) dataset from 11 breast cancer patients. Although the overall 3'UTR length of individual genes was distributed equally in tumor and non-tumor cells, we found a differential pattern of polyadenylation in gene sets between tumor and non-tumor cells. In addition, we found a differential pattern of APA across tumor types using scRNA-seq data from 3 glioblastoma patients and 1 renal cell carcinoma patients. In detail, 1,176 gene sets and 53 genes showed the distinct pattern of 3'UTR shortening and over-expression as signatures for five cell types including B lymphocytes, T lymphocytes, myeloid cells, stromal cells, and breast cancer cells. Functional categories of gene sets for cellular proliferation demonstrated concordant regulation of APA and gene expression specific to cell types. The expression of APA genes in breast cancer was significantly correlated with the clinical outcome of earlier stage breast cancer patients. We identified cell type-specific APA in single cells, which allows the identification of cell types based on 3'UTR length variation in combination with gene expression. Specifically, an immune-specific APA signature in breast cancer could be utilized as a prognostic marker of early stage breast cancer.