Unveiling Chemotherapy's Impact on Lung Cancer through Single-Cell Transcriptomics

Abstract

Background. Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and frequently affects non-smokers, especially women. It is characterized by a complex genetic profile and interactions with its microenvironment, which contribute to its aggressive and adaptable nature. Early symptoms are often subtle, leading to late diagnoses. Treatment approaches have advanced with targeted therapies and immunotherapy supplementing traditional chemotherapy and radiation. Despite these advancements, the prognosis remains variable, highlighting the need for continued research into new treatment strategies to improve outcomes. Method. In this study, we employed Single-cell RNA Sequencing (scRNA-seq) to comprehensively analyze the impact of chemotherapy on lung adenocarcinoma at the individual cell level. By comparing before and after treatment samples, we assessed the differential expression of genes and pathways, revealing insights into how different cell types within the tumour respond to chemotherapy. This approach enabled us to pinpoint specific mechanisms of drug resistance and highlight potential therapeutic targets for overcoming these challenges. Results. Our analysis uncovered substantial changes in gene expression between primary tumour cells and metastatic cells following chemotherapy. Notably, we observed that 45 pathways were shared between the top 50 upregulated pathways in the primary tumour and the top 50 downregulated pathways in the metastatic tumour post-chemotherapy. Conversely, there was no overlap between the top 50 downregulated pathways in the primary tumour and the top 50 upregulated pathways in the metastatic tumour after chemotherapy. This suggests that chemotherapy effectively downregulated the major upregulated pathways but did not upregulate the key downregulated pathways in metastatic tumours. Conclusions. Integrating single-cell transcriptomics into LUAD research offers detailed insights into the tumour's response to chemotherapy and its interaction with the immune system. This approach enhances our understanding of LUAD and aids in developing targeted and effective treatments. Based on our analysis, we hypothesize that combining chemotherapy with drugs designed to upregulate the downregulated pathways in primary tumour cells could significantly enhance treatment efficacy and improve patient outcomes.