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B7-H3 和 TIM-3 在胃型宫颈内膜腺癌中的表达:流行率、与 PD-L1 表达的相关性及预后意义。

Expression of B7-H3 and TIM-3 in gastric-type endocervical adenocarcinoma: prevalence, association with PD-L1 expression, and prognostic significance.

机构信息

Department of Pathology, Zhejiang University School of Medicine Women's Hospital, Hangzhou, Zhejiang Province, PR China.

Department of Pathology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

出版信息

J Pathol Clin Res. 2024 Jan;10(1):e345. doi: 10.1002/cjp2.345. Epub 2023 Oct 5.


DOI:10.1002/cjp2.345
PMID:37798754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10766062/
Abstract

Gastric-type endocervical adenocarcinoma (GEA) is the second most common subtype of endocervical adenocarcinoma and has a poor prognosis. Anti-programmed death-1 and anti-programmed death-ligand 1 (PD-L1) inhibitors have emerged as a major treatment option for GEA; however, data on the expression of other immune checkpoints in GEA are limited. We analyzed the expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and B7 homolog 3 protein (B7-H3) in 58 GEA and investigated their prognostic significance as well as association with PD-L1 expression and other known prognostic factors. Applying the tumor proportion score (TPS) with a cutoff of 1%, B7-H3 and TIM-3 were present in 48.3% and 17.2% of cases, respectively. Applying the combined positive score (CPS) with a cutoff of 1, TIM-3 expression was present in 70.7% of cases. Moreover, the expression of three checkpoints (B7-H3, TIM-3, and PD-L1) was incompletely overlapping. Patients with B7-H3 positive tumors (by TPS) or TIM-3 positive tumors (by TPS) had significantly worse recurrence-free survival (RFS) and overall survival (OS) (log-rank). Using CPS, patients with TIM-3 positive tumors showed significantly worse RFS (log-rank). Similarly, B7-H3 positivity (by TPS) and TIM-3 positivity (by TPS) were associated with worse RFS and OS in univariate analysis. TIM-3 positivity (by CPS) was associated with worse RFS in univariate analysis and the final Cox multivariate analysis. In conclusion, our results show that (1) B7-H3 and TIM-3 are frequently expressed in GEA and their expression overlaps incompletely with PD-L1; and (2) both B7-H3 and TIM-3 are independent negative prognostic markers in GEA.

摘要

胃型宫颈内膜腺癌(GEA)是宫颈内膜腺癌的第二大亚型,预后较差。抗程序性死亡受体-1(PD-1)和抗程序性死亡配体 1(PD-L1)抑制剂已成为 GEA 的主要治疗选择;然而,关于 GEA 中其他免疫检查点表达的数据有限。我们分析了 58 例 GEA 中 T 细胞免疫球蛋白和粘蛋白结构域包含 3 型(TIM-3)和 B7 同源物 3 蛋白(B7-H3)的表达,并研究了它们的预后意义以及与 PD-L1 表达和其他已知预后因素的关系。应用肿瘤比例评分(TPS),以 1%为截断值,B7-H3 和 TIM-3 在 48.3%和 17.2%的病例中存在。应用联合阳性评分(CPS),以 1 为截断值,TIM-3 表达存在于 70.7%的病例中。此外,三种检查点(B7-H3、TIM-3 和 PD-L1)的表达不完全重叠。B7-H3 阳性肿瘤(TPS)或 TIM-3 阳性肿瘤(TPS)患者的无复发生存率(RFS)和总生存率(OS)明显较差(对数秩)。使用 CPS,TIM-3 阳性肿瘤患者的 RFS 明显较差(对数秩)。同样,在单因素分析中,B7-H3 阳性(TPS)和 TIM-3 阳性(TPS)与 RFS 和 OS 较差相关。TIM-3 阳性(CPS)与 RFS 较差相关,且在单因素和最终 Cox 多因素分析中均如此。总之,我们的结果表明:(1)B7-H3 和 TIM-3 在 GEA 中频繁表达,其表达与 PD-L1 不完全重叠;(2)B7-H3 和 TIM-3 均为 GEA 的独立预后不良标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/0f1166351d98/CJP2-10-e345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/22d3e3829f9c/CJP2-10-e345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/a1eee73d54c5/CJP2-10-e345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/4d13bdedf77e/CJP2-10-e345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/0f1166351d98/CJP2-10-e345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/22d3e3829f9c/CJP2-10-e345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/a1eee73d54c5/CJP2-10-e345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/4d13bdedf77e/CJP2-10-e345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f6b/10766062/0f1166351d98/CJP2-10-e345-g004.jpg

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引用本文的文献

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Int J Mol Sci. 2025-3-26

[2]
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[3]
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本文引用的文献

[1]
Assessment of HER2 in Gastric-Type Endocervical Adenocarcinoma and its Prognostic Significance.

Mod Pathol. 2023-6

[2]
Discordance of PD-L1 expression in primary and metastatic ovarian high-grade serous carcinoma and its correlation with CD8 + tumor-infiltrating lymphocytes and patient prognosis.

Virchows Arch. 2023-4

[3]
Gastric-Type Adenocarcinoma of the Uterine Cervix Associated with Poor Response to Definitive Radiotherapy.

Cancers (Basel). 2022-12-28

[4]
Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers.

Gynecol Oncol. 2022-12

[5]
Prevalence and prognostic significance of PD-L1, TIM-3 and B7-H3 expression in endometrial serous carcinoma.

Mod Pathol. 2022-12

[6]
Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade.

J Immunother Cancer. 2022-6

[7]
Expression of B7 family checkpoint proteins in cervical cancer.

Mod Pathol. 2022-6

[8]
Targeting the immune checkpoint B7-H3 for next-generation cancer immunotherapy.

Cancer Immunol Immunother. 2022-7

[9]
Targeting Tim-3 in Cancer With Resistance to PD-1/PD-L1 Blockade.

Front Oncol. 2021-9-22

[10]
Programmed death-ligand 1 expression in human papillomavirus-independent cervical adenocarcinoma and its prognostic significance.

Histopathology. 2022-1

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