Abstract：
The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2 cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2 cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer.
摘要：
根据不同的病理类型或不同的临床情况，甲状腺癌患者的预后差异很大。研究免疫检查点分子PD-L1和B7-H3在高危甲状腺癌中的表达及其与临床病理特征和预后的相关性将有助于开发新的治疗策略。收集了在中国医学科学院肿瘤医院接受手术治疗的202例甲状腺癌患者的回顾性样本，包括33例间变性甲状腺癌（ATC），分化型甲状腺癌（DTC）伴远处转移（DM）21例，分化型高级别甲状腺癌（DHGTC）7例，和109例侵袭性亚型甲状腺乳头状癌（PTC）（包括28例高细胞PTC，31例弥漫性硬化性PTC，20例固体PTC，15例柱状细胞PTC，和15例hobnailPTC）。在对照组中，有32例经典PTC。免疫组化染色比较PD-L1和B7-H3蛋白在几种高危甲状腺癌与正常组织和对照组中的表达差异,并对其临床病理特征及预后相关性进行统计学分析。PD-L1在ATC中的表达(P<0.001),高电池PTC(P=0.031)，DHGTC(P=0.003)显著高于经典PTC。B7-H3在ATC中的表达(P<0.001),带DM的DTC（P=0.001），弥漫性硬化性PTC(P=0.013),柱状电池PTC（P=0.007），固体PTC（P<0.001），hobnailPTC（P<0.001），DHGTC显著高于经典PTC(P<0.001)。在ATC,PD-L1表达与甲状腺外延伸（ETE）显著相关（P=0.027），B7-H3表达与男性患者（P=0.031）和淋巴结转移（LNM）显著相关（P=0.026）。B7-H3的阳性表达(P=0.041)是ATC疾病进展的独立危险因素。B7-H3阳性表达(P=0.049),PD-L1阳性表达(P=0.015),肿瘤直径≥2cm(P=0.038)是DTC合并DM患者病情进展的独立危险因素。PD-L1阳性表达(P=0.019)和肿瘤直径≥2cm(P=0.018)是侵袭性PTC患者疾病进展的独立危险因素。B7-H3和PD-L1有望成为侵袭性甲状腺癌患者的有效预后指标，这可以帮助优化个性化治疗策略。靶向这两种分子的免疫治疗可能为高危/难治性甲状腺癌的治疗提供新的补充思路。
