Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer

TL;DR

This study explores the molecular differences in liver cancer samples to identify early signs of metastasis and improve patient treatment.

Contribution

The study introduces a novel classification of HCC samples based on tumor microenvironment components to predict prognosis and metastasis.

Findings

HCC samples were classified into five groups based on tumor microenvironment components, with Pro-Meta group showing dedifferentiation and worse outcomes.

The Pro-T group retained native hepatic metabolic activity, suggesting a less aggressive tumor phenotype.

Genomic and transcriptomic features of HCC samples correlate with metastatic potential and patient prognosis.

Abstract

Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients.

To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome.

The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

The online version contains supplementary material available at 10.1186/s12885-024-12428-x.

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