Integrative Multi-Omics Analysis for Diagnosis and Molecular Profiling of Multiple Primary Lung Cancer

Multiple primary lung cancer, the presence of two or more independent lesions in the lung, is diagnostically and therapeutically challenging as imaging and histopathology approaches often fail to accurately distinguish it from interpulmonary metastasis. Here we provide an up-to-date summary of MPLC classification based on proteomic and genomic hallmarks, obtained using immunohistochemistry and next-generation sequencing. We also highlight the recent advances in immunological research such as the promise of checkpoint inhibitors. Molecular approaches have emerged as powerful tools to overcome histological limitations, enabling more accurate subtyping and revealing striking inter-lesional mosaicism. We thus also cover emerging techniques to obtain proteomic and genomic profiles of individual lesions. Together, we demonstrate the need to integrate multi-omics data into a unified framework for MPLC characterisation and staging, which ultimately guides precision medicine.