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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Haiyu Zhou.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
197P - Clinical benefit of HER2-targeted therapies versus prior chemotherapy in refractory HER2 expressing and mutant gastrointestinal malignancies
Presenter: Vishesh Khanna
Session: Poster session 01
198P - Detection of ERBB2 (HER2) amplification by next-generation sequencing (NGS) in patients (pts) with gastrointestinal (GI) cancer
Presenter: Yunxiang Qi
Session: Poster session 01
199P - Novel machine learning (ML) algorithm to predict immunotherapy response in small cell (SCLC) and non-small cell (NSCLC) lung cancer
Presenter: Lakshya Sharma
Session: Poster session 01
200P - Precise tumor & patient selection for CDR404: A bispecific & bivalent MAGE-A4 T cell engager
Presenter: Giorgia Giacomazzi
Session: Poster session 01
201P - Afatinib for EGFR, HER2 or HER3 mutated solid tumors: A phase II Belgian precision study
Presenter: Lore Decoster
Session: Poster session 01
202P - Participant perceptions and mammography adherence from DETECT-A: The first prospective interventional trial of a multi-cancer early detection (MCED) blood test
Presenter: Nicholas Papadopoulos
Session: Poster session 01
203P - Genomic characterization of sporadic MET amplified non-small cell lung cancer (NSCLC) and association with real-world outcomes
Presenter: Ryan Gentzler
Session: Poster session 01
204P - Performance assessment of a comprehensive genomic profiling (CGP) NGS kit across multiple study laboratories
Presenter: Jonathan Choi
Session: Poster session 01
205P - A novel immunoprecipitation/PCR method for detection of plasma cfDNA fragments selectively occupied by CTCF in cancer
Presenter: Dorian Pamart
Session: Poster session 01
206P - WAYFIND-R: A global, real-world database of patients (pts) with a solid tumour profiled with next-generation sequencing (NGS)
Presenter: Jean-Yves Blay
Session: Poster session 01