Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC.

Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC.
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单细胞转录组学揭示成熟 B 细胞中的 DHX9 作为 CRC 淋巴结转移前的动态网络生物标志物

DOI:
10.1016/j.omto.2021.06.004
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发表时间:
2021-09-24
期刊:
Molecular therapy oncolytics
影响因子:
--
通讯作者:
Ling F
Ling F
中科院分区:
其他
文献类型:
--
作者:
Liu H;Zhong J;Hu J;Han C;Li R;Yao X;Liu S;Chen P;Liu R;Ling F

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越来越多的证据表明,临近肿瘤组织中的成熟B细胞作为一种中间状态,在晚期结直肠癌(CRC)中是至关重要的,这与低生存率有关。开发预测性生物标志物,在结直肠癌淋巴结转移前检测成熟B细胞的临界点,对于防止不可逆转的恶化至关重要。我们使用动态网络生物标志物(DNB)方法分析了不同阶段结直肠癌样本邻近组织中的B细胞。725个crc衍生的B细胞的单细胞分析揭示了成熟B细胞亚型的出现。使用DNB方法,我们确定了II期是淋巴结转移前的关键时期,并且DNB触发的逆转差异基因在Janus激酶(JAK)-信号转换器和转录激活因子(STAT)通路中富集,涉及B细胞免疫能力。DHX9 (DEAH-box helicase 9)是一种特异的癌旁组织DNB关键基因。从I期到III期,DHX9及其参与B细胞相关通路的近网络基因的动态表达水平在网络水平上发生逆转。综上所述,CRC邻近组织成熟B细胞中的DHX9可能是CRC进展中可预测的生物标志物和潜在的免疫靶点。基于单细胞转录组学,我们采用了一种新的方法,即动态网络生物标志物,来量化结直肠癌(CRC)邻近组织中成熟B细胞在调节网络中的免疫功能,从而预测结直肠癌转移前的关键时期,并发现特异性的生物标志物。
Increasing evidence indicates that mature B cells in the adjacent tumor tissue, both as an intermediate state, are vital in advanced colorectal cancer (CRC), which is associated with a low survival rate. Developing predictive biomarkers that detect the tipping point of mature B cells before lymph node metastasis in CRC is critical to prevent irreversible deterioration. We analyzed B cells in the adjacent tissues of CRC samples from different stages using the dynamic network biomarker (DNB) method. Single-cell profiling of 725 CRC-derived B cells revealed the emergence of a mature B cell subtype. Using the DNB method, we identified stage II as a critical period before lymph node metastasis and that reversed difference genes triggered by DNBs were enriched in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway involving B cell immune capability. DHX9 (DEAH-box helicase 9) was a specific para-cancerous tissue DNB key gene. The dynamic expression levels of DHX9 and its proximate network genes involved in B cell-related pathways were reversed at the network level from stage I to III. In summary, DHX9 in mature B cells of CRC-adjacent tissues may serve as a predictable biomarker and a potential immune target in CRC progression. Based on single-cell transcriptomics, we used a novel method named dynamic network biomarkers to quantify the immune function of mature B cells in colorectal cancer (CRC)-adjacent tissues at regulatory networks and thus to predict the critical period before CRC metastasis as well as to uncover specific biomarkers.
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发表时间: 2019-01-01
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