Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma
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...
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Elsevier
2023-01-01
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author | Xianhui Ruan Yue Huang Lin Geng Mengran Tian Yu Liu Mei Tao Xiangqian Zheng Peng Li Min Zhao |
author_facet | Xianhui Ruan Yue Huang Lin Geng Mengran Tian Yu Liu Mei Tao Xiangqian Zheng Peng Li Min Zhao |
author_sort | Xianhui Ruan |
collection | DOAJ |
description | 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, KRT7, which may be a upstream gene for the NF-κB signaling pathway. The result shows that KRT7 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. |
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language | English |
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publisher | Elsevier |
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series | Computational and Structural Biotechnology Journal |
spelling | doaj.art-6501d183eba84528a765bfbf44a109552023-12-21T07:32:25ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012153375349Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinomaXianhui Ruan0Yue Huang1Lin Geng2Mengran Tian3Yu Liu4Mei Tao5Xiangqian Zheng6Peng Li7Min Zhao8Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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; Department of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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; Corresponding authors.State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 300071 Tianjin, China; Corresponding authors.School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland 4558, Australia; Corresponding authors.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, KRT7, which may be a upstream gene for the NF-κB signaling pathway. The result shows that KRT7 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.http://www.sciencedirect.com/science/article/pii/S2001037023004014Papillary thyroid carcinomaScRNA-seqKRT7EMTNF-κB |
spellingShingle | Xianhui Ruan Yue Huang Lin Geng Mengran Tian Yu Liu Mei Tao Xiangqian Zheng Peng Li Min Zhao Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma Computational and Structural Biotechnology Journal Papillary thyroid carcinoma ScRNA-seq KRT7 EMT NF-κB |
title | Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma |
title_full | Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma |
title_fullStr | Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma |
title_full_unstemmed | Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma |
title_short | Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma |
title_sort | consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma |
topic | Papillary thyroid carcinoma ScRNA-seq KRT7 EMT NF-κB |
url | http://www.sciencedirect.com/science/article/pii/S2001037023004014 |
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