肿瘤细胞治疗研究
英文原题：Machine learning identification of NK cell immune characteristics in hepatocellular carcinoma based on single-cell sequencing and bulk RNA sequencing.
我们的研究发现，CD7 是评估免疫状态和预测肝细胞癌（HCC）患者生存的重要生物标志物；因此，它是针对 HCC 免疫治疗的潜在靶点。
背景：肝细胞癌（HCC）是一种高度恶性的肿瘤，但其免疫微环境及相关机制仍不清楚。单细胞测序可在细胞层面探索肿瘤中的免疫特征，但目前对不同免疫细胞群在肝癌进展中作用的认识有限。目的：本研究旨在基于单细胞测序和整体 RNA 测序，使用多种机器学习方法识别具有 NK 细胞免疫特征的 HCC 分子标志物。方法：我们采集 8 份正常肝组织和 8 份 HCC 肿瘤组织样本，进行单细胞 RNA 测序，以分析免疫细胞聚类和表达谱。利用多种生物信息学方法，研究 CD7 高表达 NK 细胞相关的免疫表型。此外，通过 RT-qPCR、MTS 和流式细胞术实验，验证 NK 细胞与 HCC 细胞共培养后 CD7 对 HCC 生长的作用。最后，基于 NK 细胞相关基因构建机器学习模型，建立 HCC 预后预测系统。结果：单细胞分型发现，肿瘤样本中肝细胞和 NK 细胞比例显著升高。HCC 中 CD7 表达较高，并与预后相关。更重要的是，NK 细胞中过表达 CD7 显著抑制 MHCC97 细胞活性，并增加 HCC 细胞凋亡（p < 0.05）。此外，CD7 高表达 NK 细胞与激活型免疫表型相关。结论：本研究发现，CD7 是评估 HCC 患者免疫状态和预测生存的重要生物标志物，因此也是 HCC 免疫治疗的潜在靶点。
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor; however, its immune microenvironment and mechanisms remain elusive. Single-cell sequencing allows for the exploration of immune characteristics within tumor at the cellular level. However, current knowledge regarding the roles of different immune cell populations in liver cancer progression is limited. OBJECTIVE: The main objective of this study is to identify molecular markers with NK cell immune characteristics in hepatocellular carcinoma using various machine learning methods based on Single-Cell Sequencing and Bulk RNA Sequencing. METHODS: We collected samples from eight normal liver tissues and eight HCC tumor tissues and performed single-cell RNA sequencing for immune cell clustering and expression profile analysis. Using various bioinformatic approaches, we investigated the immune phenotype associated with natural killer (NK) cells expressing high CD7 level. In addition, we verified the role of CD7 in the growth of HCC after NK cell and HCC cells cocultured by RT-qPCR, MTS and Flow cytometer experiments. Finally, we constructed a machine learning model to develop a prognostic prediction system for HCC based on NK cell-related genes. RESULTS: Through single-cell typing, we found that the proportions of hepatocytes and NK cells were significantly elevated in the tumor samples. Moreover, we found that the expression of CD7 was high in HCC and correlated with prognosis. More importantly, Overexpression of CD7 in NK cells significantly inhibited the activity of MHCC97 cells and increased the number of apoptosis of HCC cells (p < 0.05). Furthermore, we observed that NK cells with high CD7 expression were associated with an activated immune phenotype. CONCLUSION: Our study found that CD7 is an important biomarker for assessing immune status and predicting survival of HCC patients; hence, it is a potential target for immune therapy against HCC.
MEMBER ACCOUNT
登录成功会直接打开下一页。
