Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3.Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3–related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3–specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing.Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family.Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course.

Background Improving the preoperative diagnosis of cervical lymph node metastasis (LNM) will help improve the clinical outcomes of papillary thyroid carcinoma (PTC) patients. B7‐H3, as an immune checkpoint of the B7 family, is highly expressed in PTC tissues and related to LNM and prognosis. We aimed to explore the clinical values of serum B7‐H3 (sB7‐H3) in predicting LNM in PTC by a nomogram prediction model. Methods From September 2019 to May 2021, a total of 344 PTC patients with primary surgery in our hospital were enrolled in this research. Enzyme‐linked Immunosorbent Assay (ELISA) was used to detect sB7‐H3 from the peripheral blood of PTC patients and normal controls. We created a nomogram prediction model in combination with sB7‐H3 expression, clinical and ultrasound characteristics to predict LNM in the early stage. Results Gender (p = 0.001), age (p = 0.015), tumor size (p < 0.001), number of tumors (p = 0.021) and sB7‐H3 expression (p = 0.003) were independent risk factors for LNM in PTC. All the factors were included in the nomogram. The area under the curve (AUC) was 73.9% (95% CI, 68.12%–79.69%). Conclusion The nomogram is helpful in assessing the risk of LNM in PTC. sB7‐H3 has excellent potential in predicting LNM in patients with PTC as an adjunctive ultrasound tool.

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Background Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery. This is the first study of the nanogram to predict LLNM using JOHLN. Methods A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study. Results Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM) and LLMM were associated with JOHLN. And male, upper lobe tumor, multifocality, extra-nodal extension, CLNM and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on upon predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful. Conclusions JOLHN metastasis could be a clinically sensitive predictor of further LLM, especially the lateral compartment. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients. Trial registration: This study was approved by the ethics committee of the Cancer Hospital of Chinese Academy of Medical Sciences (reference number: NCC2016ST-23).