Abstract：
BACKGROUND: Cell adhesion molecules (CAMs) play a vital role in cell-cell interactions, immune response modulation, and tumor cell migration. However, the unique role of CAMs in gastric cancer (GC) remains largely unexplored.
METHODS: This study characterized the genetic alterations and mRNA expression of CAMs. The role of CD34, a representative molecule, was validated in 375 GC tissues. The activity of the CAM pathway was further tested using single-cell and bulk characterization. Next, data from 839 patients with GC from three cohorts was analyzed using univariate Cox and random survival forest methods to develop and validate a CAM-related prognostic model.
RESULTS: Most CAM-related genes exhibited multi-omics alterations and were associated with clinical outcomes. There was a strong correlation between increased CD34 expression and advanced clinical staging (P = 0.026), extensive vascular infiltration (P = 0.003), and unfavorable prognosis (Log-rank P = 0.022). CD34 expression was also found to be associated with postoperative chemotherapy and tumor immunotherapy response. Furthermore, the CAM pathway was significantly activated and mediated poor prognosis. Additionally, eight prognostic signature genes (PSGs) were identified in the training cohort. There was a substantial upregulation of the expression of immune checkpoints and a pronounced infiltration of immune cells in GC tissues with high PSG score, which is consistent with the prediction of increased sensitivity to immunotherapy. Moreover, 9 compounds from the CTRPv2 database and 13 from the Profiling Relative Inhibition Simultaneously in Mixture (PRISM) database were identified as potential therapeutic drugs for patients with GC with high PSG score.
CONCLUSIONS: Thorough understanding of CAM pathways regulation and the innovative PSG score model hold significant implications for medical diagnosis, potentially enhancing personalized treatment strategies and improving patient outcomes in GC management.
METHODS: This study characterized the genetic alterations and mRNA expression of CAMs. The role of CD34, a representative molecule, was validated in 375 GC tissues. The activity of the CAM pathway was further tested using single-cell and bulk characterization. Next, data from 839 patients with GC from three cohorts was analyzed using univariate Cox and random survival forest methods to develop and validate a CAM-related prognostic model.
RESULTS: Most CAM-related genes exhibited multi-omics alterations and were associated with clinical outcomes. There was a strong correlation between increased CD34 expression and advanced clinical staging (P = 0.026), extensive vascular infiltration (P = 0.003), and unfavorable prognosis (Log-rank P = 0.022). CD34 expression was also found to be associated with postoperative chemotherapy and tumor immunotherapy response. Furthermore, the CAM pathway was significantly activated and mediated poor prognosis. Additionally, eight prognostic signature genes (PSGs) were identified in the training cohort. There was a substantial upregulation of the expression of immune checkpoints and a pronounced infiltration of immune cells in GC tissues with high PSG score, which is consistent with the prediction of increased sensitivity to immunotherapy. Moreover, 9 compounds from the CTRPv2 database and 13 from the Profiling Relative Inhibition Simultaneously in Mixture (PRISM) database were identified as potential therapeutic drugs for patients with GC with high PSG score.
CONCLUSIONS: Thorough understanding of CAM pathways regulation and the innovative PSG score model hold significant implications for medical diagnosis, potentially enhancing personalized treatment strategies and improving patient outcomes in GC management.
摘要：
背景：细胞粘附分子（CAM）在细胞与细胞的相互作用中起着至关重要的作用，免疫反应调节，和肿瘤细胞迁移。然而,CAMs在胃癌(GC)中的独特作用在很大程度上仍未被探索.
方法：本研究表征了CAMs的遗传改变和mRNA表达。在375个GC组织中进行了验证。使用单细胞和本体表征进一步测试CAM途径的活性。接下来,本研究使用单变量Cox和随机生存森林方法对来自3个队列的839例GC患者的数据进行分析,以建立和验证CAM相关的预后模型.
结果：大多数CAM相关基因表现出多组学改变，并与临床结果相关。CD34表达增加与晚期临床分期有很强的相关性(P=0.026),广泛的血管浸润（P=0.003），预后不良（Log-rankP=0.022）。还发现CD34表达与术后化疗和肿瘤免疫治疗反应有关。此外，CAM通路被显著激活并介导不良预后。此外,在训练队列中鉴定出8个预后特征基因(PSGs).在PSG评分较高的GC组织中，免疫检查点的表达大幅上调，免疫细胞明显浸润，这与对免疫治疗敏感性增加的预测一致。此外，来自CTRPv2数据库的9种化合物和来自混合物中同时分析相对抑制(PRISM)数据库的13种化合物被鉴定为具有高PSG评分的GC患者的潜在治疗药物。
结论：对CAM通路调节和创新的PSG评分模型的透彻理解对医学诊断具有重要意义，在GC管理中可能增强个性化治疗策略并改善患者预后。
方法：本研究表征了CAMs的遗传改变和mRNA表达。在375个GC组织中进行了验证。使用单细胞和本体表征进一步测试CAM途径的活性。接下来,本研究使用单变量Cox和随机生存森林方法对来自3个队列的839例GC患者的数据进行分析,以建立和验证CAM相关的预后模型.
结果：大多数CAM相关基因表现出多组学改变，并与临床结果相关。CD34表达增加与晚期临床分期有很强的相关性(P=0.026),广泛的血管浸润（P=0.003），预后不良（Log-rankP=0.022）。还发现CD34表达与术后化疗和肿瘤免疫治疗反应有关。此外，CAM通路被显著激活并介导不良预后。此外,在训练队列中鉴定出8个预后特征基因(PSGs).在PSG评分较高的GC组织中，免疫检查点的表达大幅上调，免疫细胞明显浸润，这与对免疫治疗敏感性增加的预测一致。此外，来自CTRPv2数据库的9种化合物和来自混合物中同时分析相对抑制(PRISM)数据库的13种化合物被鉴定为具有高PSG评分的GC患者的潜在治疗药物。
结论：对CAM通路调节和创新的PSG评分模型的透彻理解对医学诊断具有重要意义，在GC管理中可能增强个性化治疗策略并改善患者预后。
