Single-cell analysis identified POSTN+ cells associated with the aggressive phenotype and risk of esophageal squamous cell carcinoma
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
Tumors are intricate and heterogeneous systems characterized by mosaic cancer cell populations with diverse expression profiles. Leveraging single-cell technologies, we employed the Scissor algorithm to delineate an epithelial subpopulation associated with the aggressive phenotype in esophageal squamous cell carcinoma (ESCC). This identified subpopulation exhibited elevated expression of genes involved in critical pathways, such as epithelial-mesenchymal transition and PI3K-Akt. Key signature genes within this subpopulation, namely CAV1, COL3A1, COL6A1, POSTN, and TAGLN, demonstrated significant upregulation concomitant with both tumorigenesis and tumor progression across independent single-cell datasets. Furthermore, we selected 1,450 expression quantitative trait loci of the top 62 signature genes of this cell subpopulation to investigate their potential in predicting ESCC risk. The results showed that the POSTN loci were predominantly associated with ESCC susceptibility. Through functional annotation and replication analyses, we identified that the rs1028728 in the POSTN promoter was significantly associated with increased ESCC risk in 7,049 ESCC cases and 8,063 controls (odds ratio = 1.29, 95% confidence interval: 1.18-1.42, p = 4.03 × 10-8). Subsequent biochemical experiments showed that the rs1028728[T] allele enhanced POSTN expression by affecting the binding of PRRX1 in the POSTN promoter. In summary, our meticulous single-cell analysis delineates an invasive epithelial subpopulation in ESCC, with POSTN emerging as an important marker for the aggressive phenotype. These findings offer more insights into potential strategies for the prevention and intervention of ESCC, enriching our understanding of this complex cancer landscape.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
HGG advances - 5(2024), 2 vom: 11. Apr., Seite 100278 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tan, Yuqian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.xhgg.2024.100278 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Tumors are intricate and heterogeneous systems characterized by mosaic cancer cell populations with diverse expression profiles. Leveraging single-cell technologies, we employed the Scissor algorithm to delineate an epithelial subpopulation associated with the aggressive phenotype in esophageal squamous cell carcinoma (ESCC). This identified subpopulation exhibited elevated expression of genes involved in critical pathways, such as epithelial-mesenchymal transition and PI3K-Akt. Key signature genes within this subpopulation, namely CAV1, COL3A1, COL6A1, POSTN, and TAGLN, demonstrated significant upregulation concomitant with both tumorigenesis and tumor progression across independent single-cell datasets. Furthermore, we selected 1,450 expression quantitative trait loci of the top 62 signature genes of this cell subpopulation to investigate their potential in predicting ESCC risk. The results showed that the POSTN loci were predominantly associated with ESCC susceptibility. Through functional annotation and replication analyses, we identified that the rs1028728 in the POSTN promoter was significantly associated with increased ESCC risk in 7,049 ESCC cases and 8,063 controls (odds ratio = 1.29, 95% confidence interval: 1.18-1.42, p = 4.03 × 10-8). Subsequent biochemical experiments showed that the rs1028728[T] allele enhanced POSTN expression by affecting the binding of PRRX1 in the POSTN promoter. In summary, our meticulous single-cell analysis delineates an invasive epithelial subpopulation in ESCC, with POSTN emerging as an important marker for the aggressive phenotype. These findings offer more insights into potential strategies for the prevention and intervention of ESCC, enriching our understanding of this complex cancer landscape | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aggressive phenotype | |
| 650 | 4 | |a ESCC | |
| 650 | 4 | |a POSTN | |
| 650 | 4 | |a PRRX1 | |
| 650 | 4 | |a Single-cell RNA-seq | |
| 650 | 4 | |a Susceptibility | |
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| 650 | 7 | |a Homeodomain Proteins |2 NLM | |
| 650 | 7 | |a POSTN protein, human |2 NLM | |
| 650 | 7 | |a Cell Adhesion Molecules |2 NLM | |
| 700 | 1 | |a Song, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jialing |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Miaoxin |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Xinying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yueping |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Linglong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shasha |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Jiang |e verfasserin |4 aut | |
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