Single Cell RNA-Seq Identifies Immune-Related Prognostic Model and Key Signature-SPP1 in Pancreatic Ductal Adenocarcinoma

Chen, Kai; Wang, Qi; Liu, Xinxin; Wang, Rui; Ma, Yue; Zhang, Shupeng; Shao, Zhijiang; Yang, Yinmo; Tian, Xiaodong

doi:10.3390/genes13101760

Cited by 16 publications

(17 citation statements)

References 49 publications

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“…This is consistent with the characteristics of immune cells infiltrated into the cancer tissue. Given the significant differences among malignant ductal cell subpopulations from different PADC patients, 34 , 35 we acknowledge the limitation of the characterization on the three tumor populations from a single patient. In future study, scRNA-seq from large cohort with sufficient normal pancreas ductal cells are necessary.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

Liu

Chen

et al. 2023

Precision Clinical Medicine

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The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1 445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA based stromal targeting biomarkers or therapy for PDAC patients.

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Section: Discussionmentioning

confidence: 99%

Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

Liu

Chen

et al. 2023

Precision Clinical Medicine

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“…For example, SPP1 expression in LUAD tissues was signi cantly higher than in normal tissues, positively correlated with TNM stage, lymph node metastasis, and depth of in ltration, and was associated with poorer prognosis by upregulating COL11A1 expression to promote cell migration and invasion (Yi et al, 2022). And in pancreatic adenocarcinoma, SPP1 expression levels were associated with patient prognosis and immune regulation (Chen et al, 2022), and in lung adenocarcinoma, SPP1 was found to be associated with drug resistance (Matsubara et al, 2022). In a recent study, researchers further investigated the level of serum SPP1 autoantibodies in patients with esophageal squamous cell carcinoma (ESCC) and showed that its expression was signi cantly upregulated compared to the normal group, suggesting that anti-SPP1 autoantibodies are a novel biomarker for the detection of ESCC , and SPP1 is important in prostate cancer (PCa), head and neck cancer (HNC), cervical squamous cell carcinoma (SCC) and other cancers (Zhang et al, 2022, Feng et al, 2022.…”

Section: Discussionmentioning

confidence: 99%

Risk prediction for Dermatomyositis-associated hepatocellular carcinoma

Zhang

Liu

et al. 2023

Preprint

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Objective To explore dermatomyositis signature genes as potential biomarkers of hepatocellular carcinoma and their associated molecular regulatory mechanisms. Methods Based on the mRNA-Seq data of dermatomyositis and hepatocellular carcinoma in public databases, five dermatomyositis signature genes were screened by LASSO regression analysis and support vector machine (SVM) algorithm, and their biological functions in dermatomyositis with hepatocellular carcinoma were investigated, and a nomogram risk prediction model for hepatocellular carcinoma was constructed and its predictive efficiency was initially evaluated. The immune profile in hepatocellular carcinoma was examined based on the CIBERSORT and ssGSEA algorithms, and the correlation between five dermatomyositis signature genes and tumor immune cell infiltration and immune checkpoints in hepatocellular carcinoma was investigated. Results The expression levels of five dermatomyositis signature genes were significantly altered in hepatocellular carcinoma and showed good diagnostic efficacy for hepatocellular carcinoma, suggesting that they may be potential predictive targets for hepatocellular carcinoma, and the risk prediction model based on five dermatomyositis signature genes showed good risk prediction efficacy for hepatocellular carcinoma and has good potential for clinical application. In addition, we also found that the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through integrin-mediated activation, which in turn regulates the development and progression of hepatocellular carcinoma. Conclusion LY6E, IFITM1, GADD45A, MT1M, and SPP1 are potential predictive targets for new-onset hepatocellular carcinoma in patients with dermatomyositis, and the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through the mediation of integrins to promote the development and progression of hepatocellular carcinoma.

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“…Chen et al 46 • SPP1 is an immune marker which is abundant in type 2 ductal cells and M2 macrophage in PDAC.…”

Section: Author Contributionsmentioning

confidence: 99%

“…Furthermore, Chen et al 46 performed scRNA‐seq and revealed M2 macrophage showed a higher expression of immune marker, SPP1, in PDAC compared to those in normal pancreatic tissues. Using multicolor immunohistochemistry (IHC) staining further analysis revealed abundant chemokines and ligands in M2 macrophage, which induced tumor development in PDAC 46 . This suggested SPP1 is a potential prognostic biomarker in PDAC, considering its abundance in type 2 ductal cells and M2 macrophage, both of which were involved in tumor‐related characteristics.…”

Section: Single‐cell Analysis In Primary Pdac Tumors and Metastatic L...mentioning

confidence: 99%

Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single‐cell analysis

Byeon,

du Toit‐Thompson,

Gillson

et al. 2023

Cancer Medicine

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BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second‐highest cause of cancer‐related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer‐associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis.MethodsThis review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single‐cell RNA‐sequencing (scRNA‐seq) and other single‐cell analysis technologies. It will further explore the emerging role of single‐cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer‐associated fibroblasts, and immune cells in PDAC progression.Results and ConclusionThe application of scRNA‐seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA‐seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in‐depth understanding of intratumoral heterogeneity in the PDAC microenvironment.

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Single Cell RNA-Seq Identifies Immune-Related Prognostic Model and Key Signature-SPP1 in Pancreatic Ductal Adenocarcinoma

Cited by 16 publications

References 49 publications

Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma

Risk prediction for Dermatomyositis-associated hepatocellular carcinoma

Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single‐cell analysis

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