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绒毛膜促性腺激素β7是癌症免疫逃逸的一个标志物。

Chorionic Gonadotropin Beta 7 is a marker of immune evasion in cancer.

作者信息

McKellar Siegen A, Pineda Jose Mario Bello, Lattupally Rohan, Codd Amy S, Newell Evan W, Lu Sydney X, Bradley Robert K

机构信息

Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

出版信息

bioRxiv. 2025 Jun 2:2025.05.28.656535. doi: 10.1101/2025.05.28.656535.

Abstract

Human chorionic gonadotropin beta (beta-hCG) is an oncofetal antigen expressed by trophoblast cells of the placenta, with minimal expression in adult somatic tissues. Numerous studies have demonstrated that beta-hCG-encoding genes are expressed in various cancers, but expression of these genes (, , , and ) across diverse cancers has not been systematically evaluated. Here, we report that CGB genes are more widely expressed across diverse cancer types than previously appreciated and that secreted beta-hCG is readily detected. In particular, CGB genes are expressed in the majority of urothelial bladder cancers, where is most frequently expressed and significantly associated with an immunosuppressed tumor microenvironment, including decreased CD8 T cell infiltration. Multiple CGB genes are associated with failure to respond to immune checkpoint inhibitor (ICI) therapy, and is particularly strongly predictive of poor prognosis. Overall, our findings indicate that beta-hCG is a clinically accessible, predictive biomarker of immunotherapeutic response.

摘要

人绒毛膜促性腺激素β(β-hCG)是一种由胎盘滋养层细胞表达的癌胚抗原,在成人体细胞组织中表达极少。大量研究表明,编码β-hCG的基因在多种癌症中表达,但这些基因(、、和)在不同癌症中的表达尚未得到系统评估。在此,我们报告CGB基因在多种癌症类型中的表达比之前认为的更为广泛,并且易于检测到分泌的β-hCG。特别是,CGB基因在大多数膀胱尿路上皮癌中表达,其中最常表达,并且与免疫抑制的肿瘤微环境显著相关,包括CD8 T细胞浸润减少。多个CGB基因与对免疫检查点抑制剂(ICI)治疗无反应相关,并且尤其强烈预测预后不良。总体而言,我们的研究结果表明β-hCG是一种临床上可获取的免疫治疗反应预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c574/12157434/59fca5060376/nihpp-2025.05.28.656535v1-f0001.jpg

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