From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics.

Secondary lymphedema (LE) can ensue after disruption of lymphatic vasculature, which may be caused by infection, surgery, or cancer treatment. Omics technologies can move the field beyond an anatomic description of lymphatic stasis by defining inflammatory, fibrotic, metabolic, lymphatic vascular, and genetic susceptibility programs that shape disease onset and progression. This review summarizes studies that use transcriptomic, proteomic, metabolomic, lipidomic, and emerging genomic or computational approaches in secondary LE. We synthesize how these datasets have identified candidate biomarkers, cell populations, signaling pathways, and therapeutic targets; highlight limitations of current platforms, samples, and bioinformatic pipelines; and propose future multi-omics strategies for diagnosis, risk stratification, and treatment development of secondary LE.