Abstract
Hepatocellular carcinoma is a primary liver cancer caused by the accumulation of genetic mutation patterns associated with epidemiological conditions. This lethal malignancy exhibits tumor heterogeneity, which is considered as one of the main reasons for drug resistance development and failure of clinical trials. Recently, single-cell technology (SCT), a new advanced sequencing technique that analyzes every single cell in a tumor tissue specimen, aids complete insight into the genetic heterogeneity of cancer. This helps in identifying and assessing rare cell populations by analyzing the difference in gene expression pattern between individual cells of single biopsy tissue which normally cannot be identified from pooled cell gene expression pattern (traditional sequencing technique). Thus, SCT improves the clinical diagnosis, treatment, and prognosis of hepatocellular carcinoma as the limitations of other techniques impede this cancer research progression. Application of SCT at the genomic, transcriptomic, and epigenomic levels to promote individualized hepatocellular carcinoma diagnosis and therapy. The current review has been divided into ten sections. Herein we deliberated on the SCT, hepatocellular carcinoma diagnosis, tumor microenvironment analysis, single-cell genomic sequencing, single-cell transcriptomics, single-cell omics sequencing for biomarker development, identification of hepatocellular carcinoma origination and evolution, limitations, challenges, conclusions, and future perspectives.
Highlights
Received: 17 December 2021An estimated 844 million people worldwide are affected by liver disease, of which liver cancer constitutes the most lethal malignancy
Based on single-cell data, the hub genes served as a correlation factor to the survival of hepatocellular carcinoma (HCC) patients and further would help in studying the molecular mechanism involved in the evolution of liver cancer [25]
HCC is a liver cancer characterized by cells exhibiting a unique gene expression profile
Summary
An estimated 844 million people worldwide are affected by liver disease, of which liver cancer constitutes the most lethal malignancy. A new technique called single-cell technology (SCT), or single-cell RNA sequencing (scRNA-seq), has filled this gap by enabling the study of single cells at the transcriptional level This has paved the way for the discovery of altered cell types such as liver progenitor cells and subtypes in diseased liver cancer samples versus normal liver samples. This technique has provided evidence that CSC subpopulations exhibited distinct molecular signatures at the tissue level while, at the single-cell level, they were phenotypically, functionally, and transcriptionally heterogeneous [11]. This review will deliver novel insights on SCT for realizing cellular heterogeneity
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