Potential molecular mechanisms of malignant evolution in pulmonary nodules: From precancerous lesions to invasive adenocarcinoma

With the widespread implementation of lung cancer screening, the detection rate of pulmonary nodules has increased annually, and pulmonary nodules have become a global public health concern. Early identification of malignant pulmonary nodules and premalignant intervention represent important clinical challenges, requiring a deeper understanding of their evolutionary characteristics. The malignant evolution of pulmonary nodules results from multi-step, multi-factorial interactions between tumors and the host, primarily involving the evolution from precancerous lesions to invasive lung adenocarcinoma. With the continuous development of multi-omics technologies, researchers have been mapping the spatiotemporal atlas of tumor initiation and progression at the molecular level. Elucidating the molecular mechanisms of malignant evolution in pulmonary nodules involves a multi-perspective analysis of tumor cells, the microenvironment, and host factors. This integrated view facilitates the identification of key biomarkers and therapeutic targets. This review summarizes the early cellular and molecular events in the malignant evolution of pulmonary nodules, aiming to provide insights for early identification and precision treatment.