Genomics Research Center, Academia Sinica, Taipei, Taiwan.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
J Pathol Clin Res. 2023 May;9(3):165-181. doi: 10.1002/cjp2.313. Epub 2023 Feb 13.
Cancer progression is influenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with poor prognosis (p = 0.024, hazard ratio = 1.44 [1.05-1.99]). A 50-gene molecular signature (prediction analysis of microarray 50) was used to subtype BCa. F11R mRNA expression significantly increased in human epidermal growth factor receptor 2 (HER2)-enriched (p = 0.0035) and basal-like BCa tumours (p = 0.0005). We evaluated F11R protein levels in two different compositions of BCa subtype patient tissue array cohorts to determine the relationship between BCa subtype and prognosis. Immunohistochemistry staining revealed that a high F11R protein level was associated with poor overall survival (p < 0.001; Taipei Medical University [TMU] cohort, p < 0.001; Kaohsiung Veterans General Hospital [KVGH] cohort) or disease-free survival (p < 0.001 [TMU cohort], p = 0.034 [KVGH cohort]) in patients with BCa. Comparison of F11R levels in different subtypes revealed the association of poor prognosis with high levels of F11R among luminal (p < 0.001 [TMU cohort], p = 0.027 [KVGH cohort]), HER2 positive (p = 0.018 [TMU cohort], p = 0.037 [KVGH cohort]), and triple-negative (p = 0.013 [TMU cohort], p = 0.037 [KVGH cohort]) BCa. F11R-based RNA microarray analysis and Ingenuity Pathway Analysis were successful in profiling the detailed gene ontology of triple-negative BCa cells regulated by F11R. The EP300 transcription factor was highly correlated with F11R in BCa (R = 0.51, p < 0.001). By analysing these F11R-affected molecules with the L1000CDs datasets, we were able to predict some repurposing drugs for potential application in F11R-positive BCa treatment.
癌症的进展受连接黏附分子（JAM）家族成员的影响。使用癌症基因组图谱数据集研究了 JAM 家族成员与不同类型癌症之间的关系。肿瘤中 F11R（F11 受体）的 mRNA 水平与 JAM-2 和 JAM-3 的表达呈负相关。这种关系是乳腺癌（BCa）所特有的，与预后不良相关（p=0.024，风险比=1.44[1.05-1.99]）。使用 50 个基因的分子特征（微阵列 50 的预测分析）对 BCa 进行亚分型。在人表皮生长因子受体 2（HER2）富集（p=0.0035）和基底样 BCa 肿瘤（p=0.0005）中，F11R mRNA 表达显著增加。我们在两个不同组成的 BCa 亚型患者组织阵列队列中评估了 F11R 蛋白水平，以确定 BCa 亚型与预后之间的关系。免疫组织化学染色显示，高 F11R 蛋白水平与总生存期不良相关（p<0.001；台北医学大学[TMU]队列，p<0.001；高雄荣民总医院[KVGH]队列）或无病生存期不良（p<0.001[TMU 队列]，p=0.034[KVGH 队列]）。比较不同亚型的 F11R 水平发现，高 F11R 与 luminal（p<0.001[TMU 队列]，p=0.027[KVGH 队列]）、HER2 阳性（p=0.018[TMU 队列]，p=0.037[KVGH 队列]）和三阴性（p=0.013[TMU 队列]，p=0.037[KVGH 队列]）BCa 患者的不良预后相关。F11R 基于 RNA 微阵列分析和 Ingenuity 通路分析成功地对 F11R 调控的三阴性 BCa 细胞的详细基因本体进行了分析。EP300 转录因子与 BCa 中的 F11R 高度相关（R=0.51，p<0.001）。通过使用 L1000CDs 数据集分析这些受 F11R 影响的分子，我们能够预测一些可能应用于 F11R 阳性 BCa 治疗的再利用药物。
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