Clinical value of SPP1 overexpression in patients with papillary thyroid carcinoma.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: In papillary THCA, elevated SPP1 expression correlates with clinicopathological features, suggesting its potential as a diagnostic marker.