利用 bulk RNA 和单细胞鉴定新型潜在生物标志物,构建用于肝癌诊断的神经网络模型。
Identification of novel potential biomarkers using bulk RNA and single cells to build a neural network model for diagnosis of liver cancer.
作者信息
Gao Yingzheng, Chen Jiahao, Du Weidong
机构信息
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310006, China.
The First Affiliated Hospital of Zhejiang, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Chinese Medical University, Hangzhou, 310006, China.
出版信息
Discov Oncol. 2025 May 12;16(1):728. doi: 10.1007/s12672-025-02420-7.
BACKGROUND
As a common cancer, liver cancer imposes an unacceptable burden on patients, but its underlying molecular mechanisms are still not fully understood. Therefore, there is an urgent need to potential biomarkers and diagnostic models for liver cancer.
METHODS
In this study, transcriptome and single-cell datasets related to liver cancer were downloaded from the UCSC Xena database and the Mendeley database, and differential analysis and weighted gene co-expression network analysis were used to find differentially expressed genes related to liver cancer. We used multiple machine algorithms to find hub genes related to liver cancer, and constructed new artificial neural network models based on their transcriptome expression patterns to assist in the diagnosis of liver cancer. Subsequently, we conducted survival analysis and immune infiltration analysis to explore the correlation between hub genes and immune cells, and used single-cell data to verify hub genes related to liver cancer.
RESULTS
This study identified MARCO, KCNN2, NTS, TERT and SFRP4 as central genes associated with liver cancer, and constructed a new artificial neural network model for molecular diagnosis of liver cancer. The diagnostic performance of the training cohort and the validation cohort was good, with the areas under the ROC curves of 1.000 and 0.986, respectively. Immune infiltration analysis determined that these central genes were closely associated with different types of immune cells. The results of immunohistochemistry and the results at the single cell level were consistent with those at the transcriptome level, and also showed obvious differences between different cell types in liver cancer and healthy states.
CONCLUSION
This study identified MARCO, KCNN2, NTS, TERT, and SFRP4 from multiple dimensions and highlighted their key roles in the diagnosis and treatment of liver cancer from multiple dimensions, providing promising biomarkers for the diagnosis of liver cancer.
背景
肝癌作为一种常见癌症,给患者带来了难以承受的负担,但其潜在的分子机制仍未完全明确。因此,迫切需要寻找肝癌的潜在生物标志物和诊断模型。
方法
在本研究中,从UCSC Xena数据库和Mendeley数据库下载了与肝癌相关的转录组和单细胞数据集,采用差异分析和加权基因共表达网络分析来寻找与肝癌相关的差异表达基因。我们使用多种机器学习算法来寻找与肝癌相关的核心基因,并基于其转录组表达模式构建新的人工神经网络模型以辅助肝癌诊断。随后,我们进行了生存分析和免疫浸润分析,以探索核心基因与免疫细胞之间的相关性,并利用单细胞数据验证与肝癌相关的核心基因。
结果
本研究确定MARCO、KCNN2、NTS、TERT和SFRP4为与肝癌相关的核心基因,并构建了一种用于肝癌分子诊断的新人工神经网络模型。训练队列和验证队列的诊断性能良好,ROC曲线下面积分别为1.000和0.986。免疫浸润分析确定这些核心基因与不同类型的免疫细胞密切相关。免疫组化结果和单细胞水平的结果与转录组水平的结果一致,并且在肝癌和健康状态下的不同细胞类型之间也显示出明显差异。
结论
本研究从多个维度鉴定了MARCO、KCNN2、NTS、TERT和SFRP4,并从多个维度突出了它们在肝癌诊断和治疗中的关键作用,为肝癌诊断提供了有前景的生物标志物。