甲状腺乳头状癌中7种细胞类型差异表达基因的一致性分析

Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma.

作者信息

Ruan Xianhui, Huang Yue, Geng Lin, Tian Mengran, Liu Yu, Tao Mei, Zheng Xiangqian, Li Peng, Zhao Min

机构信息

Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.

School of Medicine, Nankai University, Tianjin, China.

出版信息

Comput Struct Biotechnol J. 2023 Oct 27;21:5337-5349. doi: 10.1016/j.csbj.2023.10.045. eCollection 2023.

Abstract

Single-cell transcriptome sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq, enabling the dissection of cell-type-specific responses to perturbations in papillary thyroid carcinoma (PTC). However, cellular genomic features are highly heterogeneous and have a large number of genes without any expression signals, which hinders the statistical power to identify differentially expressed genes and may generate many false-positive results. To overcome this challenge, we conducted an integrative analysis on two PTC scRNA-seq datasets and cross-validated consistent differential expression. By combining results from 32 common cell types in the two studies, we identified 31 consistently differentially expressed genes (DEGs) across seven cell types, including B cells, endothelial cells, epithelial cells, monocytes, NK cells, smooth muscle cells, and T cells. Functional enrichment analysis revealed that these genes are important for the adaptive immune response and autoimmune thyroid diseases. The additional disease-free survival analysis also confirmed that these 31 genes significantly affected patient survival time in large scale thyroid cancer cohort. Furthermore, we experimentally validated one of the top consistent DEGs as a potential biomarker gene of PTC epithelial cells, , which may be a upstream gene for the NF-κB signaling pathway. The result shows that may promote thyroid cancer metastasis through the epithelial-mesenchymal transition and NF-κB signaling pathway. In summary, our single-cell transcriptome integration-based approach may provide insights into the important role of NF-κB in the underlying biology of the PTC.

摘要

单细胞转录组测序(scRNA-seq)比批量RNA测序能提供更高分辨率的细胞差异,有助于剖析甲状腺乳头状癌(PTC)中细胞类型特异性对扰动的反应。然而,细胞基因组特征高度异质,且有大量无任何表达信号的基因,这阻碍了识别差异表达基因的统计能力,并可能产生许多假阳性结果。为克服这一挑战,我们对两个PTC scRNA-seq数据集进行了综合分析,并交叉验证了一致的差异表达。通过结合两项研究中32种常见细胞类型的结果,我们在七种细胞类型中鉴定出31个一致差异表达基因(DEG),包括B细胞、内皮细胞、上皮细胞、单核细胞、NK细胞、平滑肌细胞和T细胞。功能富集分析表明,这些基因对适应性免疫反应和自身免疫性甲状腺疾病很重要。额外的无病生存分析也证实,这31个基因在大规模甲状腺癌队列中显著影响患者生存时间。此外,我们通过实验验证了其中一个最一致的DEG作为PTC上皮细胞的潜在生物标志物基因,其可能是NF-κB信号通路的上游基因。结果表明,其可能通过上皮-间质转化和NF-κB信号通路促进甲状腺癌转移。总之,我们基于单细胞转录组整合的方法可能为NF-κB在PTC基础生物学中的重要作用提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d72d/10637855/818d50e4700e/ga1.jpg

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