# NK cell–associated LncRNA signature predicts prognosis and immune landscape in hepatocellular carcinoma

## TL;DR

This study creates a model using lncRNAs linked to NK cells to predict liver cancer outcomes and understand immune interactions.

## Contribution

A novel NK cell-associated lncRNA model is developed for HCC prognosis and immune landscape analysis.

## Key findings

- A four-lncRNA model robustly predicts HCC patient outcomes.
- NK cells synergize with CD8+ T cells in the HCC tumor microenvironment.
- New HCC molecular subgroups linked to immune profiles and drug sensitivity are identified.

## Abstract

The purpose of this investigation was to develop and validate a risk model based on natural killer (NK) cell-associated lncRNAs to predict outcomes in individuals with hepatocellular carcinoma (HCC). To further explore the role of NK cells in the HCC tumor microenvironment, we leveraged single-cell RNA sequencing data and the TCGA-LIHC dataset to identify NK cell-associated lncRNAs. Using Cox regression and LASSO techniques, we pinpointed four key lncRNAs as prognostic markers for the model. The model demonstrated robust predictive power across the training set, validation set, and entire dataset. Additionally, we identified a synergistic interaction between NK cells and other immune cells, particularly CD8 + T cells, in HCC. Moreover, we uncovered novel molecular subgroups of HCC and their associations with the immune microenvironment and drug sensitivity. To further validate these findings, we performed experimental validation of the expression and function of the model lncRNAs in HCC. These results suggest that the NK cell-associated lncRNA model not only serves as an effective prognostic tool for HCC patient outcomes but also offers potential molecular targets for immunotherapy and targeted therapies.

The online version contains supplementary material available at 10.1007/s10238-026-02083-w.