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胃食管腺癌中癌/睾丸抗原的表达和共表达模式。

Cancer/testis antigen expression and co-expression patterns in gastroesophageal adenocarcinoma.

机构信息

Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY, 14206, USA.

Labcorp Oncology, 700 Ellicott Street, Buffalo, NY, 14203, USA.

出版信息

Med Oncol. 2024 Aug 14;41(9):227. doi: 10.1007/s12032-024-02475-6.

Abstract

Gastroesophageal adenocarcinoma (GEAC) poses a significant challenge due to its poor prognosis and limited treatment options. Recently, Cancer/testis antigens (CTAs) have emerged as potential therapy targets due to their high expression in tumor cells and their immunogenic nature. We aimed to explore the expression and co-expression of CTAs in GEAC. We analyzed 63 GEAC patients initially and validated our findings in 329 patients from The Cancer Genome Atlas (TCGA) database. CTA expression was measured after RNA sequencing, while clinical information, including survival outcomes and treatment details, was collected from an institutional database. Co-expression patterns among CTAs were determined using Spearman correlation analysis. The majority of the study cohort were male (87%), Caucasian (94%), and had stage IV disease (64%). CTAs were highly prevalent, ranging from 58 to 19%. The MAGE gene family showed the highest expression, consistent across both cohorts. The correlation matrix revealed a distinct cluster of significantly co-expressed genes, including MAGEA3, NY-ESO-1, and others (0.27 ≤ r ≤ 0.73). Survival analysis revealed that individual CTAs were associated with poorer survival outcomes in patients not receiving immunotherapy while showing potential for improved survival in those undergoing immunotherapy, although these findings lacked robust reliability. Our study provides a comprehensive characterization of CTA expression and co-expression in GEAC. The strong correlation among CTAs like MAGE, NY-ESO-1, and GAGE suggests a potential for therapies targeting multiple CTAs simultaneously. Further research, including prospective trials, is warranted to assess the prognostic value of CTAs and their suitability as therapeutic targets.

摘要

胃食管腺癌(GEAC)由于预后不良和治疗选择有限,是一个重大挑战。最近,由于其在肿瘤细胞中的高表达和免疫原性,癌症/睾丸抗原(CTAs)已成为潜在的治疗靶点。我们旨在探讨 CTAs 在 GEAC 中的表达和共表达。我们最初分析了 63 例 GEAC 患者,并在癌症基因组图谱(TCGA)数据库中的 329 例患者中验证了我们的发现。CTA 表达通过 RNA 测序进行测量,同时从机构数据库中收集包括生存结果和治疗细节在内的临床信息。使用 Spearman 相关分析确定 CTA 之间的共表达模式。研究队列中的大多数患者为男性(87%)、白种人(94%)和 IV 期疾病(64%)。CTAs 高度普遍,范围从 58 到 19%。MAGE 基因家族表现出最高的表达,在两个队列中都一致。相关矩阵揭示了一组明显共表达的基因,包括 MAGEA3、NY-ESO-1 和其他基因(0.27≤r≤0.73)。生存分析表明,在未接受免疫治疗的患者中,单个 CTA 与较差的生存结果相关,而在接受免疫治疗的患者中,这些 CTA 可能具有改善的生存潜力,尽管这些发现缺乏稳健的可靠性。我们的研究提供了 GEAC 中 CTA 表达和共表达的全面特征。像 MAGE、NY-ESO-1 和 GAGE 这样的 CTA 之间的强烈相关性表明同时靶向多个 CTA 的治疗潜力。需要进一步的研究,包括前瞻性试验,以评估 CTA 的预后价值及其作为治疗靶点的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b963/11324668/7ed80e380ae1/12032_2024_2475_Fig1_HTML.jpg

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