ESMO Congress 2023 | OncologyPRO

Abstract 177P

Background

Radiotherapy resistance is a major therapeutic difficulty for advanced NSCLC patients because not all patients can benefit from radiation therapy. Identifying disparities in radiosensitivity of advanced lung cancer and antagonizing the radiotherapy resistance are the challenges for clinical oncologists.

Methods

We analyzed the scRNA-seq transcriptome data of 42 patients with advanced NSCLC, including lung adenocarcinoma and lung squamous cell carcinoma, used the radiosensitivity index (RSI) to calculate the radiosensitivity intensity (RSI ^high and RSI ^low) of each cell of 11 cell types, and drew the radiosensitivity difference map of different cell types in the system. The core role of malignant cells in radiosensitivity differences in advanced NSCLC was revealed using cell cycle inference, tumor cytoTRACE score, GO/KEGG enrichment, cell-cell interactions, cellular metabolic activity, and quasi temporal trajectory joint analysis, all in accordance with the "4R" principle of radiobiology (Repair, Reoxygenation, Redistribution, Regeneration).

Results

Malignant cells differ significantly from other types of radiosensitive cells in processes such as cell cycle, aging, apoptosis, chromosomal alterations, and cellular metabolic activity. RSI ^high cells make up the majority of cells in the G2/M and S phases, and the quantity and intensity of RSI ^high cell ligand receptors increases considerably. RSI ^low cells, as an exposure factor, tend to shift from epithelial to malignant cells, leading in alterations in ligand receptor input and output patterns. Furthermore, we discovered considerable changes in the metabolic activity of RSI ^low cells in lung squamous cell carcinoma.

Conclusions

Our findings show that radiosensitivity varies in advanced NSCLC. RSI ^low cells could be a subset of malignant cells with radiotherapy resistance, driving clinical researchers to delve deeper into the detailed mechanism of advanced NSCLC.