SIMarker: Cellular similarity detection and its application to diagnosis and prognosis of liver cancer

Comput Biol Med. 2024 Mar:171:108113. doi: 10.1016/j.compbiomed.2024.108113. Epub 2024 Feb 14.

Abstract

Background: The emergence of single-cell technology offers a unique opportunity to explore cellular similarity and heterogeneity between precancerous diseases and solid tumors. However, there is lacking a systematic study for identifying and characterizing similarities at single-cell resolution.

Methods: We developed SIMarker, a computational framework to detect cellular similarities between precancerous diseases and solid tumors based on gene expression at single-cell resolution. Taking hepatocellular carcinoma (HCC) as a case study, we quantified the cellular and molecular connections between HCC and cirrhosis. Core analysis modules of SIMarker is publicly available at https://github.com/xmuhuanglab/SIMarker ("SIM" means "similarity" and "Marker" means "biomarkers).

Results: We found PGA5+ hepatocytes in HCC showed cirrhosis-like characteristics, including similar transcriptional programs and gene regulatory networks. Consequently, the genes constituting the gene expression program of these cirrhosis-like subpopulations were designated as cirrhosis-like signatures (CLS). Strikingly, our utilization of CLS enabled the development of diagnosis and prognosis biomarkers based on within-sample relative expression orderings of gene pairs. These biomarkers achieved high precision and concordance compared with previous studies.

Conclusions: Our work provides a systematic method to investigate the clinical translational significance of cellular similarities between HCC and cirrhosis, which opens avenues for identifying similar paradigms in other categories of cancers and diseases.

Keywords: Cirrhosis-like signatures; Early diagnosis and prognosis; Hepatocellular carcinoma; Orderings; Relative expression; Single-cell transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / genetics
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Precancerous Conditions*
  • Transcriptome

Substances

  • Biomarkers
  • Biomarkers, Tumor