Department of Otolaryngology, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
J Oral Pathol Med. 2022 Aug;51(7):620-629. doi: 10.1111/jop.13333. Epub 2022 Aug 4.
Lymph node metastasis (LNM) is an important cause leading to recurrence and development of head and neck carcinoma (HNC), with the precise mechanisms unclear. Thus, we aimed to identify the key genes involved in LNM and further evaluate their expressions and roles.
A cohort of HNC in the TCGA was analyzed. The study involved three phases (one screening and two validation phases). First, the differentially expressed genes regarding LNM were screened, from which a key gene was identified by a series of data mining approaches. Then, the expressions and roles of the key gene were validated in HNC through bioinformatics. Afterward, the expression of the key gene was detected by qPCR, western blot, and Immunohistochemistry based on a cell model and a tissue microarray. Further, colony formation and transwell migration and invasion assays were used to evaluate the roles of the key gene.
SPP1 was overexpressed in HNC tissues and was identified as the key gene. Overexpression of SPP1 in HNC was correlated with advanced pathological stages and T-stage, as well as the presence of LNM, which predicted poor prognosis. The expression of SPP1 was closely associated with the infiltration of immune cells in HNC, especially M2 macrophages. Lab experiments confirmed that SPP1 silence in HNC cells resulted in weakened invasive and metastatic abilities.
This study reveals that SPP1 may be a key gene associated with LNM in HNC, raising the possibility of SPP1 as a target for HNC prevention and treatment.
淋巴结转移（LNM）是导致头颈部癌（HNC）复发和发展的重要原因，其确切机制尚不清楚。因此，我们旨在确定与 LNM 相关的关键基因，并进一步评估它们的表达和作用。
分析了 TCGA 中的一组 HNC。该研究包括三个阶段（一个筛选阶段和两个验证阶段）。首先，筛选与 LNM 相关的差异表达基因，通过一系列数据挖掘方法确定一个关键基因。然后，通过生物信息学在 HNC 中验证关键基因的表达和作用。之后，基于细胞模型和组织微阵列，通过 qPCR、western blot 和免疫组织化学检测关键基因的表达。进一步，通过集落形成和 Transwell 迁移和侵袭实验评估关键基因的作用。
SPP1 在 HNC 组织中高表达，并被鉴定为关键基因。SPP1 在 HNC 中的高表达与较晚的病理分期和 T 分期以及 LNM 的存在相关，这预示着预后不良。SPP1 的表达与 HNC 中免疫细胞的浸润密切相关，尤其是 M2 巨噬细胞。实验室实验证实，在 HNC 细胞中沉默 SPP1 会导致侵袭和转移能力减弱。
本研究表明 SPP1 可能是 HNC 中与 LNM 相关的关键基因，提示 SPP1 可能成为 HNC 预防和治疗的靶点。
