Chen Qingjuan, Chen Jiankang, Lu Zuzhuang, Nian Rui, Li Wanjun, Yao Zhongqiang, Mou Shangdong, Liu Ying, Cao Xia, He Wenjing, Zhu Chenjing
Department of Oncology, 3201 Hospital of Xi'an Jiaotong University Health Science Center, Hanzhong, 723000, Shaanxi, China.
Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 40016, China.
Discov Oncol. 2024 Mar 2;15(1):57. doi: 10.1007/s12672-024-00913-5.
HPV-positive head and neck squamous cell carcinoma (HNSCC) exhibits different characteristics from HPV-negative tumors in terms of tumor development, clinical features, treatment response, and prognosis. Layilin (LAYN), which contains homology with C-type lectins, plays a critical role in tumorigenesis and cancer progression. However, the prognostic value of LAYN and the relationship between LAYN and immune infiltration levels in HPV-related HNSCC patients still require a comprehensive understanding. Herein, we aimed to assess the prognostic value of LAYN and to investigate its underlying immunological function in HPV-related HNSCC.
Through various bioinformatics methods, we analyzed the data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to explore the potential underlying oncogenic impression of LAYN, including the relevance of LAYN to survival outcomes, clinicopathological factors, immune cell infiltration, and immune marker sets in HPV-related HNSCC. The expression levels of LAYN and HPV were also verified in HNSCC patient tissues.
LAYN was differentially expressed in a variety of tumors. The expression of LAYN in HNSCC was significantly higher than that in adjacent normal tissues (P < 0.0001), and high expression of LAYN was correlated with poor overall survival (OS) in HNSCC patients (Hazard Ratio (HR) = 1.3, P = 0.035). Moreover, LAYN expression level in HPV-positive HNSCC patients was significantly lower than that in HPV-negative patients, with HPV-positive HNSCC patients displaying a trend of favorable prognosis. In addition, the relationship between LAYN expression and immune infiltration levels in HPV-positive HNSCC group was less tightly correlated than that in HPV-negative HNSCC group, and there was a strong relationship between LAYN expression and markers of M2 macrophage (P < 0.001) and exhausted T cells (P < 0.05) in HPV-negative HNSCC. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that LAYN potentially influenced tumor progression through HPV infection and other cancer-related pathways.
LAYN might contribute to tumorigenesis via its positive correlation with immune checkpoint molecules and tumor-associated macrophages (TAMs). Our study might provide a novel prognostic biomarker and latent therapeutic target for the treatment of HPV-related HNSCC.
人乳头瘤病毒（HPV）阳性的头颈部鳞状细胞癌（HNSCC）在肿瘤发生、临床特征、治疗反应和预后方面表现出与HPV阴性肿瘤不同的特征。包含与C型凝集素同源性的层粘连蛋白（LAYN）在肿瘤发生和癌症进展中起关键作用。然而，LAYN在HPV相关HNSCC患者中的预后价值以及LAYN与免疫浸润水平之间的关系仍需要全面了解。在此，我们旨在评估LAYN的预后价值，并研究其在HPV相关HNSCC中的潜在免疫功能。
通过各种生物信息学方法，我们分析了来自癌症基因组图谱（TCGA）、肿瘤免疫估计资源（TIMER）和基因表达谱交互式分析（GEPIA）数据库的数据，以探索LAYN潜在的致癌影响，包括LAYN与生存结果、临床病理因素、免疫细胞浸润以及HPV相关HNSCC中免疫标志物集的相关性。还在HNSCC患者组织中验证了LAYN和HPV的表达水平。
LAYN在多种肿瘤中差异表达。LAYN在HNSCC中的表达显著高于相邻正常组织（P < 0.0001），且LAYN的高表达与HNSCC患者较差的总生存期（OS）相关（风险比（HR）= 1.3，P = 0.035）。此外，HPV阳性HNSCC患者的LAYN表达水平显著低于HPV阴性患者，HPV阳性HNSCC患者显示出预后良好的趋势。另外，HPV阳性HNSCC组中LAYN表达与免疫浸润水平之间的关系不如HPV阴性HNSCC组紧密，且在HPV阴性HNSCC中LAYN表达与M2巨噬细胞标志物（P < 0.001）和耗竭性T细胞标志物（P < 0.05）之间存在密切关系。京都基因与基因组百科全书（KEGG）富集分析表明，LAYN可能通过HPV感染和其他癌症相关途径影响肿瘤进展。
LAYN可能通过与免疫检查点分子和肿瘤相关巨噬细胞（TAM）的正相关促进肿瘤发生。我们这项研究可能为HPV相关HNSCC的治疗提供一种新的预后生物标志物和潜在治疗靶点。
