Spatial transcriptomics reveals interferon pathway enrichment in early relapsing serous carcinoma

Spatial transcriptomics has uncovered a key insight into the complex nature of high-grade serous carcinoma (HGSC), a particularly aggressive form of ovarian cancer. Researchers have discovered that the timing of platinum-free intervals, a critical measure of treatment response, can provide valuable information for predicting patient outcomes.

By analyzing matched adnexal and omental tumor samples from nine HGSC patients, the study found distinct molecular signatures in tumors with short, medium, and long platinum-free intervals. Notably, patients with short platinum-free intervals exhibited an inflammatory phenotype driven by increased interferon response signaling, with effector interferon-stimulated gene expression present at both tumor sites.

This inflammatory response was associated with the enrichment of proliferative and cell cycle regulatory programs in medium- and long platinum-free interval tumors. The study identified three genes - complement gene C3, interferon-related genes IFI27 and BST2 - as consistently associated with short platinum-free intervals across both tumor sites.

These genes were validated using tissue-level RNA in-situ hybridization. Furthermore, a case study revealed that this inflammatory phenotype could arise as a distinct subclonal population within a single tumor. Notably, the study found that high expression of C3 was significantly associated with shorter platinum-free survival in two publicly available ovarian cancer cohorts.

These findings suggest that complement and interferon signaling play concurrent roles in treatment-naive HGSC tumors with early relapse, making them potential targets for prognostic biomarker development and therapeutic intervention.