Cao Jiawei, Zhou Tong, Chen Jiayu, Shi Dejin, Liu Xueting, Qian Changrui, Wu Guang, Yuan Shaofei, Li Lan
Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical University, Wenzhou, China.
School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
J Gastrointest Oncol. 2025 Jun 30;16(3):1287-1304. doi: 10.21037/jgo-2025-7. Epub 2025 Jun 23.
Pancreatic adenocarcinoma (PAAD) is a highly aggressive form of cancer characterized by a low survival rate. Adhesion molecule with Ig like domain family 2 (AMIGO2), a cell adhesion molecule, has been found to be expressed abnormally in various solid tumors, but its specific role in PAAD has not yet been investigated. This study aimed to investigate the potential prognostic value of AMIGO2 in pan-cancer, especially in PAAD.
RNA profiles and corresponding clinical data of PAAD patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were obtained. Kaplan-Meier survival analysis was conducted to assess the relationship between AMIGO2 expression and overall survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to evaluate the functional enrichment of AMIGO2 in PAAD. Subsequently, immune infiltration and single-cell RNA (scRNA) sequencing analyses were employed to investigate the composition of immune cells. The half maximal inhibitory concentration (IC50) value was utilized to estimate the drug sensitivity associated with AMIGO2. Finally, experiments were conducted to assess the biological function of AMIGO2 in PAAD.
AMIGO2 exhibited abnormal expression patterns and demonstrated prognostic significance in various types of cancer. AMIGO2 was observed to be up-regulated in PAAD tissues. Its high expression was indicative of a poor prognosis. Additionally, elevated level of AMIGO2 was found to be associated with mutations in and , as well as with dysregulation of key cellular processes such as "MAPK signaling" and "p53 signaling pathway". Furthermore, AMIGO2 expression exhibited correlations with the infiltration of macrophages and cancer-associated fibroblasts. PAAD patients with high AMIGO2 expression were more sensitive to BRD4 inhibitor BI-2536. The growth of PAAD cells was found to be inhibited upon knockdown of AMIGO2.
AMIGO2 was identified as prognostic factor in PAAD, suggesting its potential as a biomarker and therapeutic target for PAAD patients.
胰腺腺癌（PAAD）是一种侵袭性很强的癌症，生存率很低。免疫球蛋白样结构域家族2黏附分子（AMIGO2）是一种细胞黏附分子，已发现在各种实体瘤中表达异常，但其在PAAD中的具体作用尚未得到研究。本研究旨在探讨AMIGO2在泛癌尤其是PAAD中的潜在预后价值。
获取癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中PAAD患者的RNA谱及相应临床数据。进行Kaplan-Meier生存分析以评估AMIGO2表达与总生存期之间的关系。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析以评估AMIGO2在PAAD中的功能富集情况。随后，采用免疫浸润和单细胞RNA（scRNA）测序分析来研究免疫细胞的组成。利用半数最大抑制浓度（IC50）值来估计与AMIGO2相关的药物敏感性。最后，进行实验以评估AMIGO2在PAAD中的生物学功能。
AMIGO2在各种类型的癌症中表现出异常表达模式并具有预后意义。在PAAD组织中观察到AMIGO2上调。其高表达表明预后不良。此外，发现AMIGO2水平升高与 和 中的突变以及关键细胞过程如“MAPK信号传导”和“p53信号通路”的失调有关。此外，AMIGO2表达与巨噬细胞和癌症相关成纤维细胞的浸润相关。AMIGO2高表达的PAAD患者对BRD4抑制剂BI-2536更敏感。发现敲低AMIGO2后PAAD细胞的生长受到抑制。
AMIGO2被确定为PAAD的预后因素，表明其作为PAAD患者生物标志物和治疗靶点的潜力。
