Xin Linfeng, Li Changqing, Ni Hui, Fu Guangcheng, Qin Qin, Zhang Lin
Department of Breast and Thyroid Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Department of Breast and Thyroid Surgery, The Beiliu People's Hospital, Yulin, China.
Transl Cancer Res. 2025 Jul 30;14(7):4100-4114. doi: 10.21037/tcr-2024-2568. Epub 2025 Jul 14.
Secreted phosphoprotein 1 (SPP1) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. SPP1 is known to be involved in various cancer-related signaling pathways. Nevertheless, limited research has been conducted on the association between SPP1 and papillary thyroid carcinoma (THCA). This study aimed to investigate the expression of SPP1 in papillary THCA and its relationship with clinical relevance and immune cell infiltration.
The expression and prognosis of SPP1 in pan-cancer were analyzed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data plat forms. The differential expression of SPP1 between thyroid cancer and adjacent normal tissues was analyzed by the University of Alabama at Birmingham Cancer Data Analysis portal (UALCAN) online database. Thyroid cancer tissues and adjacent tissues were distinguished by the receiver operating characteristic (ROC) curve. The relationship between SPP1 and the signal pathway was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The correlation between SPP1 and immune cell infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER). The correlation between the expression level of SPP1 detected by immunohistochemistry and the clinical characteristics, laboratory parameters, and inflammatory indexes of patients with papillary THCA in our center was verified.
TCGA and GTEx analyses showed that SPP1 was highly expressed in thyroid cancer compared with adjacent tissues, and was related to race, cancer stages, and pathological subtypes. The area under the curve (AUC) of the ROC curve was 0.668 for distinguishing SPP1 expression levels in normal and malignant thyroid tissues. The TIMER database showed that SPP1 expression was positively correlated with B cells, CD4 T cells, neutrophils, macrophages, and dendritic cells (DC). GO and KEGG pathway analyses showed that SPP1 co-expressed genes were involved in the process of a variety of immune responses and diseases. Immunohistochemical results showed that the positive expression of SPP1 in papillary THCA was higher than that in adjacent tissues and correlated with Tumor-Capsule Distance Status, red blood cell distribution width variation coefficient (RDW-CV), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), mean corpuscular volume (MCV), and mean corpuscular-hemoglobin (MCH), and neutrophil-platelet ratio (NPR).
In papillary THCA, elevated SPP1 expression correlates with clinicopathological features, suggesting its potential as a diagnostic marker.
分泌型磷蛋白1(SPP1)是小整合素结合配体N-连接糖蛋白(SIBLING)家族的成员。已知SPP1参与多种癌症相关信号通路。然而,关于SPP1与甲状腺乳头状癌(THCA)之间关联的研究有限。本研究旨在探讨SPP1在甲状腺乳头状癌中的表达及其与临床相关性和免疫细胞浸润的关系。
使用癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据平台分析SPP1在泛癌中的表达和预后。通过阿拉巴马大学伯明翰分校癌症数据分析门户(UALCAN)在线数据库分析甲状腺癌与相邻正常组织之间SPP1的差异表达。通过受试者工作特征(ROC)曲线区分甲状腺癌组织和相邻组织。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析SPP1与信号通路之间的关系。使用肿瘤免疫估计资源(TIMER)分析SPP1与免疫细胞浸润之间的相关性。验证了通过免疫组织化学检测的SPP1表达水平与本中心甲状腺乳头状癌患者的临床特征、实验室参数和炎症指标之间的相关性。
TCGA和GTEx分析表明,与相邻组织相比,SPP1在甲状腺癌中高表达,并且与种族、癌症分期和病理亚型相关。ROC曲线的曲线下面积(AUC)为0.668,用于区分正常和恶性甲状腺组织中SPP1的表达水平。TIMER数据库显示,SPP1表达与B细胞、CD4 T细胞、中性粒细胞、巨噬细胞和树突状细胞(DC)呈正相关。GO和KEGG通路分析表明,SPP1共表达基因参与多种免疫反应和疾病过程。免疫组织化学结果显示,SPP1在甲状腺乳头状癌中的阳性表达高于相邻组织,并且与肿瘤-包膜距离状态、红细胞分布宽度变异系数(RDW-CV)、血小板分布宽度(PDW)、平均血小板体积(MPV)、大血小板比率(P-LCR)、平均红细胞体积(MCV)和平均红细胞血红蛋白(MCH)以及中性粒细胞-血小板比率(NPR)相关。
在甲状腺乳头状癌中,SPP1表达升高与临床病理特征相关,提示其作为诊断标志物的潜力。