Single cell RNA sequencing – a valuable tool for cancer immunotherapy: a mini review

Kodous, Ahmad S.; Balaiah, Meenakumari; Ramanathan, Priya

doi:10.1515/oncologie-2023-0244

Cited by 8 publications

(1 citation statement)

References 43 publications

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“…High-throughput transcriptomics enabled by bulk RNA determines average gene expression profiles of all the cells in a cluster, and signal-cell RNA sequencing (scRNA-seq) clarifies the heterogeneity of cell types ( Kodous, Balaiah & Ramanathan, 2023 ). Recently, scRNA-seq research has been widely applied in many research fields including in the studies of tumor ecosystems ( Yan et al, 2021 ; Hornburg et al, 2021 ), immune-related diseases ( Lin et al, 2022 ; Wang et al, 2021 ) and neuroscience ( Galiakberova et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients’ prognosis

Wang,

Chen,

et al. 2024

PeerJ

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Background Patients with lung adenocarcinoma (LUAD) often develop a poor prognosis. Currently, researches on prognostic and immunotherapeutic capacity of aneuploidy-related genes in LUAD are limited. Methods Genes related to aneuploidy were screened based on bulk RNA sequencing data from public databases using Spearman method. Next, univariate Cox and Lasso regression analyses were performed to establish an aneuploidy-related riskscore (ARS) model. Results derived from bioinformatics analysis were further validated using cellular experiments. In addition, typical LUAD cells were identified by subtype clustering, followed by SCENIC and intercellular communication analyses. Finally, ESTIMATE, ssGSEA and CIBERSORT algorithms were employed to analyze the potential relationship between ARS and tumor immune environment. Results A five-gene ARS signature was developed. These genes were abnormally high-expressed in LUAD cell lines, and in particular the high expression of CKS1B promoted the proliferative, migratory and invasive phenotypes of LUAD cell lines. Low ARS group had longer overall survival time, higher degrees of inflammatory infiltration, and could benefit more from receiving immunotherapy. Patients in low ASR group responded more actively to traditional chemotherapy drugs (Erlotinib and Roscovitine). The scRNA-seq analysis annotated 17 cell subpopulations into seven cell clusters. Core transcription factors (TFs) such as CREB3L1 and CEBPD were enriched in high ARS cell group, while TFs such as BCLAF1 and UQCRB were enriched in low ARS cell group. CellChat analysis revealed that high ARS cell groups communicated with immune cells via SPP1 (ITGA4-ITGB1) and MK (MDK-NCl) signaling pathways. Conclusion In this research, integrative analysis based on the ARS model provided a potential direction for improving the diagnosis and treatment of LUAD.

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Section: Introductionmentioning

confidence: 99%

Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients’ prognosis

Wang,

Chen,

et al. 2024

PeerJ

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Engrailed 2 facilitates progression of triple-negative and HER2-enriched breast cancer by binding to enhancer region of Tenascin-C

Chen,

Yin

2024

Discov Onc

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Engrailed 2 (EN2) is a homeodomain-containing protein whose aberrant expression is observed in various cancer types, yet its role in breast cancer remains unclear. This study investigates the roles and mechanisms of EN2 in breast cancer progression. Using online dataset analysis, we assessed the correlation between EN2 expression and breast cancer progression and chemotherapeutic sensitivity. Functional assays, including RT-qPCR, Western blot, cell viability, transwell migration and invasion, spheroid formation, and flow cytometry, were conducted to explore EN2's role. Mechanistic insights were obtained through luciferase reporter assays, ChIP, and Caspase 3 activity detection. Our results showed that EN2 is highly expressed in breast cancer patients, negatively correlating with survival rates and positively with disease progression and reduced chemotherapy sensitivity. Functional experiments confirmed EN2's oncogenic role, and it was found to promote the expression of the oncogenic Tenascin-C (TNC) gene. Notably, EN2 directly interacts with the super-enhancer region within the TNC locus. Elevated TNC expression mitigated the effects of EN2 knockdown on breast cancer cell progression. Our study unveils a novel mechanism by which EN2 regulates the TNC locus super-enhancer, thereby activating oncogenic pathways in breast cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s12672-024-01471-6.

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Single-cell data revealed the regulatory mechanism of TNK cell heterogeneity in liver metastasis from gastric cancer

Gao,

Liu,

Tao

et al. 2024

Discov Onc

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Aim The present work set out to classify cell subpopulations related to liver metastasis from gastric cancer (GC) and the mechanisms of their interactions with other immune cell subpopulations. Background GC is characterized by a high degree of heterogeneity and liver metastasis. Exploring the mechanism of liver metastasis of GC from the perspective of heterogeneity of the tumor microenvironment (TME) might help improve the efficacy of GC treatment. Objective Based on the cellular subpopulation characteristics of GC with liver metastasis, the regulatory mechanisms contributing to GC progression were analyzed, with special focuses on the roles of signaling pathways, transcription factors (TFs) and ligand–receptor pairs. Methods The GSE163558 dataset was downloaded from the Gene Expression Omnibus (GEO) database to collect single-cell transcriptomic data of GC patients and their metastasis groups for cell clustering and relevant analyses. Differentially expressed genes (DEGs) in the GC and GC liver metastasis groups were screened and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. SCENIC analysis was used to mine TFs that affected cellular subpopulations during liver metastasis from GC. The relative expression levels of TFs in GC were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the regulation of the TFs on the migration and invasion of GC cells. Interaction network between the cellular subpopulations was developed applying CellChat. Results Single-cell clustering was performed to group six major cell subpopulations, namely, Myeloid cells, B cells, Mast cells, Epithelial cells, Fibroblasts, and TNK cells, among which the number of TNK cells was significantly increased in the GC liver metastasis group. Differentially enriched pathways of TNK cells between GC and GC liver metastasis groups mainly included IL-17 and Pi3k–Akt signaling pathways. TNK cell subsets could be further categorized into CD8 T cells, Exhausted T cells, NK cells, NKT cells, and Treg cells, with the GC liver metastasis group showing significantly more CD8 T cells and NKT cells. FOS and JUNB were the TFs of TNK cell marker genes that contributed to liver metastasis from GC and the invasion and migration of GC cell lines. Significant differences in immune cell communication ligand–receptor pairs existed between the GC and GC liver metastasis groups. Conclusion This study revealed the critical role of TNK cell subsets in GC with liver metastasis applying single-cell transcriptomics analysis. The findings provided an important theoretical basis for developing novel therapies to inhibit liver metastasis from GC.

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Single cell RNA sequencing – a valuable tool for cancer immunotherapy: a mini review

Cited by 8 publications

References 43 publications

Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients’ prognosis

Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients’ prognosis

Engrailed 2 facilitates progression of triple-negative and HER2-enriched breast cancer by binding to enhancer region of Tenascin-C

Single-cell data revealed the regulatory mechanism of TNK cell heterogeneity in liver metastasis from gastric cancer

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