研究动态
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间充质干细胞相关基因在泛癌中临床结局的综合分析。

Integrated Analysis of Clinical Outcome of Mesenchymal Stem Cell-related Genes in Pan-cancer.

发表日期:2024
作者: Mingzhe Jiang, Dantong Zhu, Dong Zhao, Yongye Liu, Jia Li, Zhendong Zheng
来源: Epigenetics & Chromatin

摘要:

尽管间充质干细胞(MSC)在组织再生等工程医学中的应用众所周知,但新的证据不断出现,表明间充质干细胞还可以促进癌症进展、转移和耐药性。然而,尚未对 MSC 进行大规模队列分析来揭示其对癌症患者预后的影响。我们提出 MSC 评分作为泛癌不良预后的新替代指标。我们使用单样本基因集富集分析来将 MSC 相关基因量化为特征评分,并使用多元 Cox 回归分析将特征评分识别为癌症的潜在独立预后标记。利用 TIDE 算法和神经网络评估 MSC 相关基因对免疫治疗的预测准确性。在 33 种癌症类型中,正常样本和肿瘤样本之间的 MSC 相关基因表达存在显着差异。 Cox回归分析表明MSC评分可作为肾乳头状细胞癌、间皮瘤、神经胶质瘤和胃腺癌的独立预后标志物。成纤维细胞的丰度也比基质评分更能代表 MSC 评分。我们的研究结果支持结合使用TIDE算法和神经网络来预测MSC相关基因用于免疫治疗的准确性。我们全面表征了泛癌中MSC的转录组、基因组和表观遗传学,揭示了肿瘤中MSC的串扰微环境,特别是与癌症相关的成纤维细胞。有人提出,这可能是癌症免疫治疗耐药的关键来源之一。Bentham Science Publishers。
Although the application of mesenchymal stem cells (MSCs) in engineered medicine, such as tissue regeneration, is well known, new evidence is emerging that shows that MSCs can also promote cancer progression, metastasis, and drug resistance. However, no large-scale cohort analysis of MSCs has been conducted to reveal their impact on the prognosis of cancer patients.We propose the MSC score as a novel surrogate for poor prognosis in pan-cancer.We used single sample gene set enrichment analysis to quantify MSC-related genes into a signature score and identify the signature score as a potential independent prognostic marker for cancer using multivariate Cox regression analysis. TIDE algorithm and neural network were utilized to assess the predictive accuracy of MSC-related genes for immunotherapy.MSC-related gene expression significantly differed between normal and tumor samples across the 33 cancer types. Cox regression analysis suggested the MSC score as an independent prognostic marker for kidney renal papillary cell carcinoma, mesothelioma, glioma, and stomach adenocarcinoma. The abundance of fibroblasts was also more representative of the MSC score than the stromal score. Our findings supported the combined use of the TIDE algorithm and neural network to predict the accuracy of MSC-related genes for immunotherapy.We comprehensively characterized the transcriptome, genome, and epigenetics of MSCs in pan-cancer and revealed the crosstalk of MSCs in the tumor microenvironment, especially with cancer-related fibroblasts. It is suggested that this may be one of the key sources of resistance to cancer immunotherapy.Bentham Science Publishers.