Cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma: Clinical significance, prognostic impact, and correlation with microvessel density

Abstract

Cancer-associated fibroblasts (CAFs) play pivotal roles in facilitating tumor growth, recurrence, and metastasis. Nevertheless, studies examining the clinicopathological significance of CAFs and microvessel density (MVD) in hypopharyngeal squamous cell carcinoma (HPSCC), as well as their implications for prognosis, are scarce. Tissue samples from 96 HPSCC patients were subjected to immunohistochemistry (IHC) for CAF markers (including FAP and α-SMA) and MVD (characterized by the CD31 marker). Bioinformatics analysis was conducted to elucidate the potential mechanisms through which CAFs exert their functions. Compared with normal hypopharyngeal tissues, HPSCC tissues exhibited a greater number of CAFs and greater MVD. The high-MVD group demonstrated increased levels of FAP and α-SMA expression, increased CAF density, and an elevated rate of lymph node metastasis. Both CAF enrichment and high MVD were significantly associated with adverse clinicopathological features in patients, thereby leading to reduced overall survival. Additionally, both MVD and lymph node metastasis were identified as being independent prognostic factors that markedly increase patient mortality risk. Bioinformatics analyses revealed that CAFs may affect tumor progression, angiogenesis, and metastasis by the PI3K-Akt, KRAS, and Hedgehog signaling pathways, as well as through mechanisms such as epithelial-mesenchymal transition and ECM remodeling. CD19 may act as a potential marker for how CAFs affect the prognosis of head and neck squamous cell carcinomas. In summary, our findings indicate that CAFs and the MVD may significantly influence the prognosis of HPSCC patients. Angiogenesis and immunosuppression may represent the central mechanism through which CAFs affect prognosis, as CAFs facilitate angiogenesis and immunosuppression, thereby driving tumor progression and metastasis.