利用机器学习整合单细胞和批量 RNA 测序数据,构建和验证胃癌中新型细胞粘附分子相关的预后模型。
Utilizing machine learning to integrate single-cell and bulk RNA sequencing data for constructing and validating a novel cell adhesion molecules related prognostic model in gastric cancer.
发表日期:2024 Aug 12
作者:
Chenbin Chen, Xietao Chen, Yuanbo Hu, Bujian Pan, Qunjia Huang, Qiantong Dong, Xiangyang Xue, Xian Shen, Xiaodong Chen
来源:
COMPUTERS IN BIOLOGY AND MEDICINE
摘要:
细胞粘附分子(CAM)在细胞间相互作用、免疫反应调节和肿瘤细胞迁移中发挥着至关重要的作用。然而,CAM 在胃癌 (GC) 中的独特作用在很大程度上仍未得到探索。本研究表征了 CAM 的遗传改变和 mRNA 表达。 CD34 作为代表性分子的作用已在 375 个 GC 组织中得到验证。使用单细胞和批量表征进一步测试了 CAM 途径的活性。接下来,使用单变量 Cox 和随机生存森林方法分析来自三个队列的 839 名 GC 患者的数据,以开发和验证 CAM 相关预后模型。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 (P = 0.026)、广泛血管浸润 (P = 0.003) 和不良预后 (Log-rank P = 0.022) 之间存在很强的相关性。 CD34 表达还被发现与术后化疗和肿瘤免疫治疗反应相关。此外,CAM 通路显着激活并介导不良预后。此外,在训练队列中还发现了八个预后特征基因(PSG)。 PSG 评分高的 GC 组织中,免疫检查点表达显着上调,免疫细胞明显浸润,这与免疫治疗敏感性增加的预测一致。此外,CTRPv2数据库中的9种化合物和混合相对抑制同时分析(PRISM)数据库中的13种化合物被确定为高PSG评分GC患者的潜在治疗药物。对CAM通路调节的透彻理解和创新的PSG评分模型为对医学诊断具有重大影响,有可能增强个性化治疗策略并改善 GC 管理中的患者预后。版权所有 © 2024。由 Elsevier Ltd 出版。
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.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.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.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.Copyright © 2024. Published by Elsevier Ltd.