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Abstract：
Immunotherapy is currently one of the most viable therapies for head and neck squamous cell carcinoma (HNSCC), characterized by high immune cell infiltration. The Wnt-signaling inhibitor and immune activation mediator, Dickkopf-1 (DKK1), has a strong correlation with tumor growth, tumor microenvironment, and, consequently, disease prognosis. Nevertheless, it is still unclear how DKK1 expression, HNSCC prognosis, and tumor-infiltrating lymphocytes are related. To better understand these associations, we examined how DKK1 expression varies across different tumor and normal tissues. In our study, we investigated the association between DKK1 mRNA expression and clinical outcomes. Next, we assessed the link between DKK1 expression and tumor immune cell infiltration. Additionally, using immunohistochemistry, we evaluated the expression of DKK1 in 15 healthy head and neck tissue samples, and the expression of CD3, CD4, and DKK1 in 27 HNSCC samples. We also explored aberrant DKK1 expression during tumorigenesis. DKK1 expression was remarkably higher in HNSCC tissues than in healthy tissues, and was shown to be associated with tumor stage, grade, lymph node metastasis, histology, and a dismal clinical prognosis in HNSCC. DKK1 expression in HNSCC tissues was inversely correlated with CD3+ (P < 0.0001) and CD4+ (P < 0.0001) immune cell infiltration, while that in immune cells was inversely associated with HNSCC prognosis. These findings offer a bioinformatics perspective on the function of DKK1 in HNSCC immunotherapy and provide justification for clinical research on DKK1-targeted HNSCC treatments. DKK1 is a central target for improving the efficacy of HNSCC immunotherapy.
摘要：
免疫治疗是目前头颈部鳞状细胞癌（HNSCC）最可行的治疗方法之一，特点是高免疫细胞浸润。Wnt信号抑制剂和免疫激活介质，Dickkopf-1(DKK1),与肿瘤生长有很强的相关性，肿瘤微环境,and,因此,疾病预后。然而，目前尚不清楚DKK1如何表达，HNSCC预后，和肿瘤浸润淋巴细胞有关。为了更好地理解这些关联，我们检查了DKK1表达在不同肿瘤和正常组织中的变化。在我们的研究中,我们研究了DKK1mRNA表达与临床结局之间的关联.接下来,我们评估了DKK1表达与肿瘤免疫细胞浸润之间的联系。此外,使用免疫组织化学，我们评估了15个健康头颈部组织样本中DKK1的表达，27例HNSCC样本中CD3、CD4和DKK1的表达。我们还探索了肿瘤发生过程中DKK1的异常表达。DKK1在HNSCC组织中的表达显著高于健康组织,并被证明与肿瘤分期有关，grade,淋巴结转移,组织学,HNSCC的临床预后不佳。HNSCC组织中DKK1表达与CD3+(P<0.0001)和CD4+(P<0.0001)免疫细胞浸润呈负相关,而免疫细胞中的免疫细胞与HNSCC预后呈负相关。这些发现为DKK1在HNSCC免疫治疗中的功能提供了生物信息学观点，并为DKK1靶向HNSCC治疗的临床研究提供了依据。DKK1是提高HNSCC免疫治疗疗效的核心靶点。
