Kalvapudi Sukumar, Pachimatla Akhil Goud, Seager R J, Conroy Jeffrey, Pabla Sarabjot, Mukherjee Sarbajit
Roswell Park Comprehensive Cancer Center.
LabCorp (United States).
Res Sq. 2024 Jun 20:rs.3.rs-4499622. doi: 10.21203/rs.3.rs-4499622/v1.
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 Pearson 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 58-19%. 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.
胃食管腺癌（GEAC）因其预后不良和治疗选择有限而构成重大挑战。最近，癌/睾丸抗原（CTA）因其在肿瘤细胞中的高表达及其免疫原性而成为潜在的治疗靶点。我们旨在探讨CTA在GEAC中的表达及共表达情况。我们最初分析了63例GEAC患者，并在来自癌症基因组图谱（TCGA）数据库的329例患者中验证了我们的发现。通过RNA测序测量CTA表达，同时从机构数据库收集包括生存结果和治疗细节在内的临床信息。使用Pearson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%），且患有IV期疾病（64%）。CTA高度普遍存在，范围为58%至19%。MAGE基因家族表达最高，在两个队列中均一致。相关矩阵显示了一组明显共表达的基因，包括MAGEA3、NY - ESO - 1等（0.27≤r≤0.73）。生存分析显示，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显示出改善生存的潜力，尽管这些发现缺乏强大的可靠性。我们的研究全面描述了CTA在GEAC中的表达及共表达情况。MAGE、NY - ESO - 1和GAGE等CTA之间的强相关性表明同时靶向多个CTA进行治疗具有潜力。有必要进行进一步的研究，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。
