Ovarian serous cystadenocarcinoma (OV) remains a lethal malignancy with complex tumor microenvironment (TME) dynamics and heterogeneous therapeutic responses. Unfolded protein response (UPR) signaling has been implicated in tumor progression and therapy resistance, yet its role in OV remains underexplored. Leveraging single‐cell RNA sequencing (scRNA‐seq) data and bulk RNA‐seq cohorts, we deciphered the cellular composition of the OV microenvironment and identified UPR‐related molecular subtypes. Through integrative analysis, we pinpointed KRT16 as a key prognostic gene associated with adverse outcomes. High KRT16 expression correlated with distinct mutational profiles, altered immune infiltration, and reduced sensitivity to targeted agents such as PD0325901 and dasatinib. Our findings nominate KRT16 as a novel biomarker and potential therapeutic target in OV, linking UPR activity to tumor aggression, cytoskeletal remodeling, immune modulation (including myeloid‐derived suppressor cell recruitment), and therapy resistance.
Yang et al. (Thu,) studied this question.