揭示SMAD家族成员6作为睾丸生殖细胞肿瘤预后和免疫疗法反应的新型生物标记物的作用。

IF 3.2 2区 医学 Q1 ANDROLOGY
Andrology Pub Date : 2025-02-25 DOI:10.1111/andr.70015
Huawei Lin, Xiaowen Lin, Peisheng Huang, Xiaoxue Yu, Jianming Liu, Liangliang Huang, Yanni Wei, Jiahong Chen, Zhouda Cai, Le Zhang, Junhong Deng, Zhuoyuan Lin, Yu Zheng, Jianming Lu
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引用次数: 0

摘要

背景与目的:睾丸生殖细胞瘤(TGCT)虽罕见,但常见于20-40岁的年轻男性。近年来,TGCT的全球患病率逐渐上升,有12-30%的患者出现复发和转移。然而,目前还没有可靠的生物标志物来准确预测TGCT患者的预后。因此,确定TGCT风险分层的新生物标志物是当务之急。材料和方法:我们使用来自多个中心的TGCT样本,通过差异表达分析、Cox回归和生存分析,确定了一种新的预后生物标志物(SMAD家族成员6 [SMAD6])。然后采用免疫组化(IHC)方法评估SMAD6在正常睾丸组织和TGCT样本中的表达水平。最后,我们研究了SMAD6与其生物学特性、突变景观、免疫细胞浸润和免疫治疗反应之间的关系。结果:我们的研究确定SMAD6是TGCT预后的危险因素。免疫组化显示SMAD6在TGCT组织中显著表达。功能富集分析表明SMAD6可能参与肿瘤进展相关通路的激活和免疫相关通路的抑制。此外,SMAD6高表达与CD8+ T细胞浸润减少相关,而SMAD6低表达的患者从免疫治疗中获益更多。讨论与结论:本研究强调SMAD6可能对TGCT预后和免疫治疗反应预测有用,为个性化医疗策略提供了一个有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unveiling SMAD family member 6 as a novel biomarker for prognosis and immunotherapy response in testicular germ cell tumors.

Background and objectives: Despite its rarity, testicular germ cell tumor (TGCT) is commonly diagnosed in young males aged 20-40. In recent years, the global prevalence of TGCT has gradually increased, with 12-30% of patients experiencing relapse and metastasis. However, there are currently no reliable biomarkers for accurately predicting the prognosis of TGCT patients. Therefore, identifying novel biomarkers for risk stratification in TGCT is an immediate priority.

Materials and methods: Using TGCT samples from multiple centers, we identified a novel prognostic biomarker (SMAD family member 6 [SMAD6]) through differential expression analysis, Cox regression, and survival analysis. Immunohistochemistry (IHC) was then employed to evaluate SMAD6 expression levels in normal testicular tissues and TGCT samples. Finally, we examined the relationship between SMAD6 and its biological characteristics, mutation landscape, immune cell infiltration, and response to immunotherapy.

Results: Our study identified SMAD6 as a risk factor for TGCT prognosis. IHC revealed significant expression of SMAD6 in TGCT tissues. Functional enrichment analysis indicated that SMAD6 may contribute to the activation of tumor progression-related pathways and suppression of immune-related pathways. Additionally, high SMAD6 expression was correlated with reduced CD8+ T cell infiltration, while patients with low SMAD6 expression benefited more from immunotherapy.

Discussion and conclusions: This study highlights the potential of SMAD6 may be useful for TGCT prognosis and immunotherapy response prediction, offering a promising target for personalized medicine strategies.

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来源期刊
Andrology
Andrology ANDROLOGY-
CiteScore
9.10
自引率
6.70%
发文量
200
期刊介绍: Andrology is the study of the male reproductive system and other male gender related health issues. Andrology deals with basic and clinical aspects of the male reproductive system (gonads, endocrine and accessory organs) in all species, including the diagnosis and treatment of medical problems associated with sexual development, infertility, sexual dysfunction, sex hormone action and other urological problems. In medicine, Andrology as a specialty is a recent development, as it had previously been considered a subspecialty of urology or endocrinology
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