Integrating single-cell and bulk RNA sequencing reveals CK19 + cancer stem cells and their specific SPP1 + tumor-associated macrophage niche in HBV-related hepatocellular carcinoma
© 2023. Asian Pacific Association for the Study of the Liver..
PURPOSE: Cytokeratin 19-positive cancer stem cells (CK19 + CSCs) and their tumor-associated macrophages (TAMs) have not been fully explored yet in the hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
EXPERIMENTAL DESIGN: Single-cell RNA sequencing was performed on the viable cells obtained from 11 treatment-naïve HBV-associated HCC patients, including 8 CK19 + patients, to elucidate their transcriptomic landscape, CK19 + CSC heterogeneity, and immune microenvironment. Two in-house primary HCC cohorts (96 cases-related HBV and 89 cases with recurrence), TCGA external cohort, and in vitro and in vivo experiments were used to validate the results.
RESULTS: A total of 64,581 single cells derived from the human HCC and adjacent normal tissues were sequenced, and 11 cell types were identified. The result showed that CK19 + CSCs were phenotypically and transcriptionally heterogeneous, co-expressed multiple hepatics CSC markers, and were positively correlated with worse prognosis. Moreover, the SPP1 + TAMs (TAM_SPP1) with strong M2-like features and worse prognosis were specifically enriched in the CK19 + HCC and promoted tumor invasion and metastasis by activating angiogenesis. Importantly, matrix metalloproteinase 9 (MMP9) derived from TAM_SPP1, as the hub gene of CK19 + HCC, was activated by the VEGFA signal.
CONCLUSIONS: This study revealed the heterogeneity and stemness characteristics of CK19 + CSCs and specific immunosuppressive TAM_SPP1 in CK19 + HCC. The VEGFA signal can activate TAM_SPP1-derived MMP9 to promote the invasion and metastasis of CK19 + HCC tumors. This might provide novel insights into the clinical treatment of HCC patients.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
|---|---|
| Enthalten in: |
Hepatology international - 18(2024), 1 vom: 01. Feb., Seite 73-90 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yang, Cheng-Lei [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 02.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s12072-023-10615-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366498592 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366498592 | ||
| 003 | DE-627 | ||
| 005 | 20240302232422.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240108s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12072-023-10615-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1314.xml |
| 035 | |a (DE-627)NLM366498592 | ||
| 035 | |a (NLM)38159218 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yang, Cheng-Lei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Integrating single-cell and bulk RNA sequencing reveals CK19 + cancer stem cells and their specific SPP1 + tumor-associated macrophage niche in HBV-related hepatocellular carcinoma |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 02.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. Asian Pacific Association for the Study of the Liver. | ||
| 520 | |a PURPOSE: Cytokeratin 19-positive cancer stem cells (CK19 + CSCs) and their tumor-associated macrophages (TAMs) have not been fully explored yet in the hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) | ||
| 520 | |a EXPERIMENTAL DESIGN: Single-cell RNA sequencing was performed on the viable cells obtained from 11 treatment-naïve HBV-associated HCC patients, including 8 CK19 + patients, to elucidate their transcriptomic landscape, CK19 + CSC heterogeneity, and immune microenvironment. Two in-house primary HCC cohorts (96 cases-related HBV and 89 cases with recurrence), TCGA external cohort, and in vitro and in vivo experiments were used to validate the results | ||
| 520 | |a RESULTS: A total of 64,581 single cells derived from the human HCC and adjacent normal tissues were sequenced, and 11 cell types were identified. The result showed that CK19 + CSCs were phenotypically and transcriptionally heterogeneous, co-expressed multiple hepatics CSC markers, and were positively correlated with worse prognosis. Moreover, the SPP1 + TAMs (TAM_SPP1) with strong M2-like features and worse prognosis were specifically enriched in the CK19 + HCC and promoted tumor invasion and metastasis by activating angiogenesis. Importantly, matrix metalloproteinase 9 (MMP9) derived from TAM_SPP1, as the hub gene of CK19 + HCC, was activated by the VEGFA signal | ||
| 520 | |a CONCLUSIONS: This study revealed the heterogeneity and stemness characteristics of CK19 + CSCs and specific immunosuppressive TAM_SPP1 in CK19 + HCC. The VEGFA signal can activate TAM_SPP1-derived MMP9 to promote the invasion and metastasis of CK19 + HCC tumors. This might provide novel insights into the clinical treatment of HCC patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer stem cell | |
| 650 | 4 | |a Hepatitis B virus | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Heterogeneity | |
| 650 | 4 | |a Keratin 19 | |
| 650 | 4 | |a Matrix metalloproteinase 9 | |
| 650 | 4 | |a SPP1 | |
| 650 | 4 | |a Single-cell transcriptome sequencing | |
| 650 | 4 | |a Tumor-associated macrophage | |
| 650 | 4 | |a VEGFA signal | |
| 650 | 7 | |a Matrix Metalloproteinase 9 |2 NLM | |
| 650 | 7 | |a EC 3.4.24.35 |2 NLM | |
| 650 | 7 | |a Keratin-19 |2 NLM | |
| 650 | 7 | |a SPP1 protein, human |2 NLM | |
| 650 | 7 | |a Osteopontin |2 NLM | |
| 650 | 7 | |a 106441-73-0 |2 NLM | |
| 700 | 1 | |a Song, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jun-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jun-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Nan-Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Hang-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuan-Kuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Zhan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun-Duo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Min-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Guo-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hong-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Lu-Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qiu-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Bang-De |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Hepatology international |d 2007 |g 18(2024), 1 vom: 01. Feb., Seite 73-90 |w (DE-627)NLM190585528 |x 1936-0541 |7 nnns |
| 773 | 1 | 8 | |g volume:18 |g year:2024 |g number:1 |g day:01 |g month:02 |g pages:73-90 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12072-023-10615-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 18 |j 2024 |e 1 |b 01 |c 02 |h 73-90 | ||