Expression profiling and prognostic prediction of treatment response in non-small cell lung cancer

Abstract

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aimed to identify molecular changes in NSCLC patients based on their response to treatment. Using tumor and matched normal samples, we performed a retrospective, comprehensive spatial transcriptomic analysis of proven malignant NSCLC cells treated with immunotherapy. Proliferative and metabolic pathways were upregulated, while immune pathways were downregulated in both responders and non-responders during the normal-to-carcinoma transition. Comparing responder and non-responder groups and tumor/normal expression changes, enriched proliferative, metabolic and immune pathways resembling carcinogenesis were observed. Some genes in the proliferative pathways indicated a poor prognosis by leading edge analysis. Notable immunotherapy response-associated modules and specific genes such as GNA11, WBP2, MMAB, KRT18 in NSCLC and VPS37B, MGAT4B, HIPK2, TNK2 in lung squamous cell carcinoma emerged as potential predictive biomarkers. These findings provide insight into the mechanisms of immunotherapy in NSCLC and identify potential therapeutic targets.