Immunotherapy may be more appropriate for ERBB2 low-expressing extramammary paget's disease patients: a prognosis analysis and exploration of targeted therapy and immunotherapy of extramammary paget's disease patients.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-10-03 DOI:10.1007/s00262-024-03846-8
Jiawen Yang, Yurong Chen, Xiuyuan Zhang, Ziyan Tong, Shanshan Weng, Ning Zhu, Ying Yuan
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Abstract

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy characterized by its uncertain etiology and metastatic potential. Surgery remains the first-line clinical treatment for EMPD, but the efficacy of radiotherapy and chemotherapy remains to be fully evaluated, and new therapies for EMPD are urgently needed. In this study, we initially screened 815 EMPD patients in the Surveillance, Epidemiology, and End Results (SEER) database and analyzed their clinical features and prognostic factors. Using the dataset from the Genome Sequence Archive (GSA) database, we subsequently conducted weighted gene coexpression network analysis (WGCNA), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analyses, grouping the samples based on EMPD disease status and the levels of ERBB2 expression. The prognostic analysis based on the SEER database identified increased age at diagnosis, distant metastasis, and receipt of radiotherapy as independent risk factors for EMPD. Moreover, our results indicated that patients who received chemotherapy had worse prognoses than those who did not, highlighting the urgent need for novel treatment approaches for EMPD. Functional analysis of the GSA-derived dataset revealed that EMPD tissues were significantly enriched in immune-related pathways compared with normal skin tissues. Compared with those with high ERBB2 expression, tissues with low ERBB2 expression displayed greater immunogenicity and enrichment of immune pathways, particularly those related to B cells. These findings suggest that patients with low ERBB2 expression are likely to benefit from immunotherapy, especially B-cell-related immunotherapy.

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免疫疗法可能更适合ERBB2低表达的乳腺外乳头状瘤病患者:乳腺外乳头状瘤病患者的预后分析及靶向治疗和免疫疗法探索。
乳腺外Paget病(EMPD)是一种罕见的皮肤恶性肿瘤,其特点是病因不明确且具有转移潜力。手术仍是 EMPD 的一线临床治疗方法,但放疗和化疗的疗效仍有待全面评估,EMPD 急需新疗法。在这项研究中,我们首先从监测、流行病学和最终结果(SEER)数据库中筛选了815名EMPD患者,并分析了他们的临床特征和预后因素。利用基因组序列档案(GSA)数据库中的数据集,我们随后进行了加权基因共表达网络分析(WGCNA)、基因组富集分析(GSEA)、基因组变异分析(GSVA)和免疫浸润分析,并根据EMPD疾病状态和ERBB2表达水平对样本进行了分组。基于SEER数据库的预后分析发现,诊断时年龄增大、远处转移和接受过放疗是EMPD的独立危险因素。此外,我们的研究结果表明,接受化疗的患者比未接受化疗的患者预后更差,这凸显了对新型 EMPD 治疗方法的迫切需求。GSA衍生数据集的功能分析显示,与正常皮肤组织相比,EMPD组织的免疫相关通路明显丰富。与ERBB2高表达的组织相比,ERBB2低表达的组织显示出更强的免疫原性和更丰富的免疫通路,尤其是与B细胞相关的通路。这些研究结果表明,ERBB2表达量低的患者有可能从免疫疗法中获益,尤其是与B细胞相关的免疫疗法。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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