# Molecular mechanism of radiation tolerance in lung adenocarcinoma cells using single‐cell RNA sequencing

## TL;DR

This study identifies cell subpopulations in lung adenocarcinoma linked to radiation tolerance, offering insights into improving radiotherapy outcomes.

## Contribution

The study identifies specific cell subpopulations associated with radiotherapy tolerance in lung adenocarcinoma using single-cell RNA sequencing.

## Key findings

- HIST1H1D+ A549 and PIF1+ A549 cell subpopulations are linked to radiotolerance in lung adenocarcinoma.
- TP53 mutations are more common in patients who have undergone radiotherapy compared to those who have not.
- Expression of cell cycle-related genes increases with prolonged radiation treatment in these subpopulations.

## Abstract

The efficacy of radiotherapy, a cornerstone in the treatment of lung adenocarcinoma (LUAD), is profoundly undermined by radiotolerance. This resistance not only poses a significant clinical challenge but also compromises patient survival rates. Therefore, it is important to explore this mechanism for the treatment of LUAD. Multiple public databases were used for single‐cell RNA sequencing (scRNA‐seq) data. We filtered, normalized and downscaled scRNA‐seq data based on the Seurat package to obtain different cell subpopulations. Subsequently, the ssGSEA algorithm was used to assess the enrichment scores of the different cell subpopulations, and thus screen the cell subpopulations that are most relevant to radiotherapy tolerance based on the Pearson method. Finally, pseudotime analysis was performed, and a preliminary exploration of gene mutations in different cell subpopulations was performed. We identified HIST1H1D+ A549 and PIF1+ A549 as the cell subpopulations related to radiotolerance. The expression levels of cell cycle‐related genes and pathway enrichment scores of these two cell subpopulations increased gradually with the extension of radiation treatment time. Finally, we found that the proportion of TP53 mutations in patients who had received radiotherapy was significantly higher than that in patients who had not received radiotherapy. We identified two cellular subpopulations associated with radiotherapy tolerance, which may shed light on the molecular mechanisms of radiotherapy tolerance in LUAD and provide new clinical perspectives.