Abstract

Analysis of single-cell RNA sequencing (scRNA-seq) data of immune cells from the tumor microenvironment (TME) may identify tumor progression biomarkers. This study was designed to investigate the prognostic value of differentially expressed genes (DEGs) in intrahepatic cholangiocarcinoma (ICC) using scRNA-seq. We downloaded the scRNA-seq data of 33,991 cell samples, including 17,090 ICC cell samples and 16,901 ICC adjacent tissue cell samples regarded as normal cells. scRNA-seq data were processed and classified into 20 clusters. The immune cell clusters were extracted and processed again in the same way, and each type of immune cells was divided into several subclusters. In total, 337 marker genes of macrophages and 427 marker genes of B cells were identified by comparing ICC subclusters with normal subclusters. Finally, 659 DEGs were obtained by merging B cell and macrophage marker genes. ICC sample clinical information and gene expression data were downloaded. A nine-prognosis-related-gene (PRG) signature was established by analyzing the correlation between DEGs and overall survival in ICC. The robustness and validity of the signature were verified. Functional enrichment analysis revealed that the nine PRGs were mainly involved in tumor immune mechanisms. In conclusion, we established a PRG signature based on scRNA-seq data from immune cells of patients with ICC. This PRG signature not only reflects the TME immune status but also provides new biomarkers for ICC prognosis.

Highlights

  • Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent type of primary liver cancer worldwide (Massarweh and El-Serag, 2017) and accounts for 10–15% of malignant hepatic tumors.ICC arises from bile duct epithelial cells and is characterized by insidious onset and rapid progression

  • 33,991 cell samples that comprised 17,090 tumor cells and 16,901 normal cells from eight patients with ICC were obtained from the Gene Expression Omnibus (GEO) database (Table 1)

  • Some studies have illustrated the relationship between immune cells and ICC progression (Sulpice et al, 2016), but most of these studies screened for biomarkers by comparing tissue sequencing results of tumor and non-tumor tissues

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Summary

Introduction

Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent type of primary liver cancer worldwide (Massarweh and El-Serag, 2017) and accounts for 10–15% of malignant hepatic tumors. ICC arises from bile duct epithelial cells and is characterized by insidious onset and rapid progression. The 3- and 5-year survival rates for ICC are only 30 and 18%, respectively (Bartella and Dufour, 2015). Only 30% of patients with ICC have the opportunity to undergo. Prognostic Signature in ICC database (GSE107943) in August 2020. All the data in this study were obtained directly from the public database, and the relevant guidelines were strictly followed, allowing ethical approval to be exempted.

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