Cancer/testis antigen expression and co-expression patterns in Gastroesophageal Adenocarcinoma.

Sukumar Kalvapudi, Akhil Goud Pachimatla, R J Seager, Jeffrey Conroy, Sarabjot Pabla, Sarbajit Mukherjee
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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 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.

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胃食管腺癌中癌症/睾丸抗原的表达和共表达模式
胃食管腺癌(GEAC)预后不良,治疗方案有限,是一项重大挑战。最近,癌症/睾丸抗原(CTAs)因其在肿瘤细胞中的高表达和免疫原性而成为潜在的治疗靶点。我们旨在探索 CTAs 在 GEAC 中的表达和共表达情况。我们初步分析了 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研究结果。CTA的表达是在RNA测序后测定的,而临床信息,包括生存结果和治疗细节,则是从一个机构数据库中收集的。通过皮尔逊相关分析确定了CTA之间的共表达模式。研究队列中的大多数人是男性(87%)、白种人(94%)和 IV 期患者(64%)。CTA的发病率很高,从58%到19%不等。MAGE 基因家族的表达量最高,这在两个队列中都是一致的。相关性矩阵显示,MAGEA3、NY-ESO-1等基因有明显的共表达(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,则显示出改善生存的潜力,尽管这些发现缺乏可靠的可靠性。我们的研究全面描述了CTA在GEAC中的表达和共表达情况。MAGE、NY-ESO-1和GAGE等CTA之间的强相关性表明,同时针对多个CTA的疗法具有潜力。有必要开展进一步的研究,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宜性。
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