Single-cell RNA-seq reveals transcriptional landscape and intratumor heterogenicity in gallbladder cancer liver metastasis microenvironment

Zhang, Yigang; Wang, You; Li, Xiangyu; Wang, Peng; Sha, Bowen; Yuan, Liang; Qiu, Jiannan; Zhou, Jiang; Hu, Haoran; Lu, Ling

doi:10.21037/atm-21-2227

Cited by 13 publications

(4 citation statements)

References 46 publications

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“…Recent single-cell RNA sequencing (scRNA-seq) technology has enabled the large-scale profiling of transcriptomic states/stochasticity at the single-cell resolution level and provides insights into transcriptional stochasticity. CytoTRACE is a newly developed computational algorithm for predicting the differentiation status of malignant cell population based on scRNA-seq data [21][22][23]. Here, we used publicly available scRNA-seq data to characterize the stemness phenotype and immunogenicity of high stemness in iCCA.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing

Bian

Wang

et al. 2022

Stem Cells International

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Cancer stem cells (CSCs) are responsible for long-term maintenance of tumors and thought to play a role in treatment resistance. The interaction between stemness and immunogenicity of CSCs in the intrahepatic cholangiocarcinoma (iCCA) is largely unknown. Here, we used single-cell transcriptomic data to study immunogenicity of malignant cells in human iCCA. Using an established computerized method CytoTRACE, we found significant heterogeneity in stemness/differentiation states among malignant cells. We demonstrated that the high stemness malignant cells express much lower levels of major histocompatibility complex II molecules when compared to low stemness malignant cells, suggesting a role of immune evasion in high stemness malignant cells. In addition, high stemness malignant iCCA cells exhibited significant expression of certain cytokine members, including CCL2, CCL20, CXCL1, CXCL2, CXCL6, CXCL8, TNFRSF12A, and IL6ST, indicating communication with surrounding immune cells. These results indicate that high stemness malignant cells retain their intrinsic immunological feature that facilitate the escape of immune surveillance.

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Section: Introductionmentioning

confidence: 99%

Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing

Bian

Wang

et al. 2022

Stem Cells International

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“…While analyzing the HE-stained images, we found varied changes of lymphocytic cell infiltration in the DI field. Growing evidence has established that T lymphocytes, especially CD8 + cytotoxic T lymphocytes (CTL), function to protect tumor development as the main anti-tumor immune effector cells [30,31]. The prognostic value of CD3 + and CD8 + TILs in patients with GBC has been reported in a number of studies, including our previous publications [32][33][34], but the clinical significance and prognostic value of TILs homing to the front liver area have not been investigated.…”

Section: Correlation Of Tils Density In DI Area With Clinical Factors...mentioning

confidence: 99%

Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion

Qiu,

Liu,

et al. 2024

Int. J. Med. Sci.

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Background: Direct liver invasion (DI) is a predominant pathway of gallbladder cancer (GBC) metastasis, but the molecular alterations associated with DI remain addressed. This study identified specific genes correlated with DI, which may offer a potential biomarker for the diagnosis and prognosis of advanced GBC. Methods: RNA samples from 3 patients with DI of GBC were used for RNA-seq analysis. Differentially expressed genes and metabolic pathways between primary tumor (T) and DI tissue was used to analyze aberrant gene expressions. Immunohistochemistry (IHC) of fatty acid binding protein 1 (FABP1) in 62 patients with DI was engaged to evaluate its association with clinicopathological characteristics and prognosis. IHC of CD3 + and CD8 + T cells was analyzed for their correlation with FABP1 expression, clinicopathological features and prognosis. Univariate and multivariate Cox hazards regression analyses were performed to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: FABP1 mRNA levels were significantly upregulated in DI region compared to T tissue. IHC results showed identical results with elevated FABP1 (p < 0.0001). Expression of FABP1 in DI region was significantly associated with lymph node metastasis (P = 0.028), reduced DFS (P = 0.013) and OS (P = 0.022); in contrast, its expression in T region was not associated with clinicopathological characteristics and prognosis (P > 0.05). The density of CD8 + T cells in DI region with higher FABP1 expression was significantly lower than that with lower FABP1 expression (p = 0.0084). Multivariate analysis unveiled those hepatic metastatic nodules (HR = 3.35, 95%CI: 1.37-8.15, P = 0.008) and FABP1 expression in DI region (HR = 2.01, 95%CI: 1.05-3.88, P = 0.036) were high risk factors for OS, and FABP1(HR = 2.05, 95%CI: 1.04-4.06, P = 0.039) was also a high risk factor for DFS. Conclusions: Elevated expression of FABP1 in DI region serves as a potential prognostic biomarker for advanced GBC with DI.

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“…Advances in single-cell RNA sequencing (scRNA-seq) technology have enabled accurate and in-depth studies of cellular heterogeneity and the tumor microenvironment (TME) (6,7). Recently, some studies have provided new insights into the characteristics of metastatic tumors (8)(9)(10). In the specific context of CC, our previous study has established the transcriptional profiles of normal and tumor cells in CC using scRNA-seq methods (11).…”

Section: Introductionmentioning

confidence: 99%

Integrated single-cell transcriptome analysis of the tumor ecosystems underlying cervical cancer metastasis

Liu

Yang

et al. 2022

Front. Immunol.

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Cervical cancer (CC) is one of the most frequent female malignancies worldwide. However, the molecular mechanism of lymph node metastasis in CC remains unclear. In this study, we investigated the transcriptome profile of 51,507 single cells from primary tumors, positive lymph nodes (P-LN), and negative lymph nodes (N-LN) using single-cell sequencing. Validation experiments were performed using bulk transcriptomic datasets and immunohistochemical assays. Our results indicated that epithelial cells in metastatic LN were associated with cell- cycle-related signaling pathways, such as E2F targets, and mitotic spindle, and immune response-related signaling pathways, such as allograft rejection, IL2_STAT5_signaling, and inflammatory response. However, epithelial cells in primary tumors exhibited high enrichment of epithelial-mesenchymal translation (EMT), oxidative phosphorylation, and interferon alpha response. Our analysis then indicated that metastasis LN exhibited an early activated tumor microenvironment (TME) characterized by the decrease of naive T cells and an increase of cytotoxicity CD8 T cells, NK cells, FOXP3+ Treg cells compared with normal LN. By comparing the differently expressed gene of macrophages between tumor and metastatic LN, we discovered that C1QA+ MRC1low macrophages were enriched in a tumor, whereas C1QA+ MRC1high macrophages were enriched in metastatic LN. Finally, we demonstrated that cancer-associated fibroblasts (CAFs) in P-LN were associated with immune regulation, while CAFs in tumor underwent EMT. Our findings offered novel insights into the mechanisms of research, diagnosis, and therapy of CC metastasis.

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Single-cell RNA-seq reveals transcriptional landscape and intratumor heterogenicity in gallbladder cancer liver metastasis microenvironment

Cited by 13 publications

References 46 publications

Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing

Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing

Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion

Integrated single-cell transcriptome analysis of the tumor ecosystems underlying cervical cancer metastasis

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