PO.ET01.03 · 实验与分子治疗
利用TCGA数据分析消化道癌抗原表达及其与患者生存结局的相关性或关联
Correlation of GI cancer antigens expression or association with patient survival outcomes using TCGA data
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：消化系统（包括食管、胃、结肠、直肠、胰腺、肝脏和胆道）的癌症占全球癌症负担的很大一部分。近来，肿瘤相关抗原（TAAs）已被证明在靶向癌症治疗和作为标志物方面具有用途。尽管已鉴定出许多消化道癌相关的TAAs，但如果能够同时靶向多种抗原谱，治疗有望得到改善。本研究首先考察了八种知名的消化道癌特异性TAAs的表达：MMP7、TACSTD2、FOLR1、EPCAM、AADAT、MSLN、CLDN18和CEACAM5；然后研究了它们彼此之间以及与患者生存的关系。
方法：采用癌症基因组图谱（TCGA）数据库；使用UALCAN分析TAA在正常和肿瘤样本中的表达谱及其显著性。还分析了每种TAA对生存率（Kaplan-Meier）的影响及其显著性。生存曲线和显著性采用log-rank检验计算。最后，从基因表达谱交互分析（GEPIA）门户获取了七种癌症中八种抗原之间的Pearson相关性。
结果：在各类消化道癌中，TAA表达与正常组织存在差异。MMP7和MSLN是最常见的上调抗原。除LIHC（其中MMP7、EPCAM和AADAT下调）外，大多数癌症表现出三种或以上抗原升高。八种TAAs中仅有五种与生存相关：STAD中的EPCAM和MMP7、LIHC中的FOLR1和CLDN18、ESCA中的EPCAM，以及PAAD中的MSLN。除TACSTD2（与所有ESCA抗原呈负相关）外，相关性大多为弱至中等。
结论：由于MMP7和MSLN在消化道癌中广泛上调，这些TAAs可作为泛消化道治疗的潜在靶点进一步研究。具有多个与生存相关的高影响上调抗原的癌症，可能适合采用多抗原抗体或CAR-T治疗，例如针对STAD的EPCAM和MMP7。此外，TAAs之间的弱相关性提示可能存在相对独立的机制调控它们的表达。因此，这意味着靶向单一抗原的治疗可能并不完全有效。
查看英文原文 English abstract
Background: Cancers of the GI system, including the esophagus, stomach, colon, rectum, pancreas, liver, and biliary tract, comprise a significant portion of the global cancer burden. Recently, tumor-associated antigens (TAAs) have been shown to be useful in targeted cancer therapies and as markers. Although many GI cancer-related TAAs have been identified, treatments could be improved if they could target multiple antigen profiles simultaneously. This study first examines the expression of eight well-known GI cancer-specific TAAs: MMP7, TACSTD2, FOLR1, EPCAM, AADAT, MSLN, CLDN18, and CEACAM5; then it investigates their relationships with each other and with patient survival.
Methods: The Cancer Genome Atlas (TCGA) database; UALCAN was used to analyze the expression profile of TAA in normal and tumor samples, along with their significance. The effects of each TAA on survivability (Kaplan-Meier) and their significance were also analyzed. Survival plots and significance were calculated using log-rank tests. Lastly, Pearson correlations between the eight antigens across all seven cancers were obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) portal.
Results: Across GI cancers show that TAA expression varies from that in normal tissue. MMP7 and MSLN are the most commonly upregulated. Most cancers exhibit three or more antigens that are increased, except for LIHC, where MMP7, EPCAM, and AADAT are downregulated. Only five of eight TAAs correlate with survival: EPCAM and MMP7 in STAD, FOLR1 and CLDN18 in LIHC, EPCAM in ESCA, and MSLN in PAAD. Correlations are mostly weak to moderate, except TACSTD2, which is negatively correlated with all ESCA antigens.
Conclusion: Since MMP7 and MSLN are broadly upregulated in GI cancers, these TAAs could be studied further as potential targets for pan-GI therapies. Cancers with multiple high-impact upregulations associated with survival may be suitable for treatment with multi-antigen antibody or CAR-T therapies, such as EPCAM and MMP7 for STAD. Additionally, the weak correlations among the TAAs suggest that somewhat independent mechanisms might regulate their expression. Therefore, this implies that therapies targeting a single antigen may not be fully effective.
利益披露 Disclosure
C. Wu, None..
S. H. Shaham, None..
M. Tripathi, None.