Analyzing the extracellular matrix-dominated immune landscape of high-grade serous ovarian cancer to determine prognosis and guide therapy

Abstract

Abstract High grade serous ovarian cancer (HGSOC) is associated with a poor prognosis and a high recurrence rate. For high-risk patients, personalized treatment augmentation and clinically relevant molecular prognostic indicators are required. As extracellular matrix (ECM) are very active component of the tumor microenvironment, influencing the behavior and metastatic potential of tumor cells, understanding ECM function may aid in the development of useful diagnostics and innovative medicines for HGSOC. Using univariate Cox regression analysis, we identified 71 ECM genes associated with prognosis in seven HGSOC populations. Cox proportional hazards regression with lasso penalty was utilized to validate the ECMscore signature of 14 genes. Analyses of Cox regression indicate that ECMscore is an excellent indication for prognostic classification in the most prevalent malignancies, including HGSOC. In addition, we found that patients with a higher ECMscore exhibited more active stromal and carcinogenic activation pathways, including apical Surface, Notch signaling, apical Junction, Wnt signaling, epithelial-mesenchymal transition, TGF-ß signaling, and angiogenesis. In contrast, patients with a relatively low ECMscore had more active immune-related pathways, such as interferon alpha response, interferon-gamma response, and inflammatory response. The relationship between the ECMscore and genome anomalies was further examined. In addition, the interaction between ECMscore and immune microenvironment components and signals in HGSOC was examined in greater detail. As one of the hubs, the expression of MGP and its relationship to FBN1 were validated using qRT-PCR on HGSOC samples. The utility of ECMscore in predicting the prospective clinical success of immunotherapy and its capacity to guide the selection of chemotherapeutic medicines were also investigated. Additionally, pan-cancer research showed similar results. In conclusion, a comprehensive evaluation of the ECM may enable the identification of immune activation and help patients in HGSOC and pan-cancer to obtain the proper therapy.