PARs in the inflammation-cancer transformation of CRC

Lv, Jianyu; Liu, Jinguo; Chao, Guanqun; Zhang, Shuo

doi:10.1007/s12094-022-03052-x

Cited by 7 publications

(5 citation statements)

References 87 publications

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“…Previous studies have demonstrated that CF patients are susceptible to infection and develop an inflammatory response ( 26 ), which is also present in the SGs ( 38 ). We found that the CF-SGEPs had elevated expression of BDKRB1 and F2R, which are positively associated with inflammation ( 39 , 40 ). In summary, the CF-SGEPs exhibited a strong association with the phenotype of CF patients.…”

Section: Discussionmentioning

confidence: 83%

Differentiation and Characterization of Cystic Fibrosis Transmembrane Conductance Regulator Knockout Human Pluripotent Stem Cells into Salivary Gland Epithelial Progenitors

Yan,

Zhang,

Zhang

et al. 2023

Int J Stem Cells

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The differentiation of pluripotent stem cells has been used to study disease mechanisms and development. We previously described a method for differentiating human pluripotent stem cells (hPSCs) into salivary gland epithelial progenitors (SGEPs). Here, cystic fibrosis transmembrane conductance regulator (CFTR) knockout hPSCs were differentiated into SGEPs derived from CFTR knockout hESCs (CF-SGEPs) using the same protocol to investigate whether the hPSC-derived SGEPs can model the characteristics of CF. CF-a disease that affects salivary gland (SG) function-is caused by mutations of the CFTR gene. Firstly, we successfully generated CFTR knockout hPSCs with reduced CFTR protein expression using the CRISPR-Cas9 system. After 16 days of differentiation, the protein expression of CFTR decreased in SGEPs derived from CFTR knockout hESCs (CF-SGEPs). RNA-Seq revealed that multiple genes modulating SG development and function were down-regulated, and positive regulators of inflammation were up-regulated in CF-SGEPs, correlating with the salivary phenotype of CF patients. These results demonstrated that CFTR suppression disrupted the differentiation of hPSC-derived SGEPs, which modeled the SG development of CF patients. In summary, this study not only proved that the hPSC-derived SGEPs could serve as manipulable and readily accessible cell models for the study of SG developmental diseases but also opened up new avenues for the study of the CF mechanism.

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Section: Discussionmentioning

confidence: 83%

Differentiation and Characterization of Cystic Fibrosis Transmembrane Conductance Regulator Knockout Human Pluripotent Stem Cells into Salivary Gland Epithelial Progenitors

Yan,

Zhang,

Zhang

et al. 2023

Int J Stem Cells

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“…In terms of cellular communication, epithelial cells with a high-risk score exhibited heightened interactions with various cell types, acting as stronger senders, receivers, mediators, and in uencers. And all associated with cancer growth, migration, metastasis, stemness, and intrinsic drug resistance [23,[25][26][27]. These ndings suggested the potential of the risk signature as a prognostic tool closely re ecting a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…The spatial transcriptomics data of four colorectal cancer samples were used [22]. We used the R package Seurat to process space transcriptomics data and used log-normalization to standardize data [23]. We used functions SelectIntegrationFeatures, FindIntegrationAnchors, and IntegrateData to remove batch effects and integrate Seurat object into a single ST dataset.…”

Section: Spatial Transcriptomics Data Preparationmentioning

confidence: 99%

“…6H), only high-risk epithelial cells interacted with other cells and acted as receiver,and in uencer, while low-risk epithelial cells do not. As a result, these differences in high-risk epithelial cells may participate in cancer growth, migration, metastasis, stemness and intrinsic drug resistance [23,[25][26][27].…”

Section: Differences In Biological Function and Cellular Communicatio...mentioning

confidence: 99%

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Integrate multiple machine learning algorithms to establish a prognostic model of risk signature for programmed cell death and hypoxia and conduct multi-omics analysis of risk signatures in colorectal cancer

Ma,

Peng,

Wei

et al. 2024

Preprint

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Background Colorectal cancer (CRC) poses a significant challenge due to its high heterogeneity, making accurate prognosis prediction complex. Hypoxia plays a central role in influencing cell death mechanisms, tumorigenesis and progression. However, the prognostic significance of the interplay between hypoxia and cell death in CRC needs further investigation. Methods We employed a robust computational framework to explore the relationship between hypoxia and 18 cell death patterns in a global cohort of 1294 CRC patients from four multicenter cohorts. Thirteen commonly used machine learning algorithms were employed to develop optimal-performing hypoxia-associated programmed cell death risk signatures. Additionally, risk signature genes were screened at both the single-cell and spatial transcriptome levels using AddModuleScore analysis to enhance the identification of the signature. Results The risk signature, composed of 63 influential genes, conducted significant performance in predicting in CRC patients. The high-risk signature correlates significantly with pathways related to tumor occurrence, progression, and increased immune cells infiltration. The risk signature scores closely correlated with various immune cells proportions. At the single-cell level, high-risk epithelial cells were closely linked to pathways involving tumor occurrence, development, and drug resistance. High-risk epithelial cells exhibit enhanced communication with different cell types, acting as stronger Senders, Mediators, Receivers, and Influencers, promoting tumor progression. There are significant differences in copy number variation (CNV) and developmental trajectory between high-risk and low-risk epithelial cells. Moreover, we identified these risk signatures at the spatial transcriptome level, revealing their high expression throughout the entire tumor tissue. Conclusion Our robust machine learning framework highlights the prognostic potential of hypoxia-associated programmed cell death risk signatures in CRC. Integrating these signatures into prognosis prediction offers a unique opportunity for clinical intelligence and innovative management approaches.

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“…Since Balkwill first put forward the hypothesis of the correlation between inflammatory response and tumor, he believed that “tumor originates from chronic inflammation.” [23] Since then, a large number of studies have confirmed that it is closely related to the prognosis of malignant tumors such as lung cancer, colorectal cancer, and Breast cancer. [24–26] Inflammation plays an important role in many processes such as tumor development, invasion, and metastasis, and it is listed as one of the top 10 biological characteristics of tumor cells. [27] As an indicator of body inflammation, PLR can reflect the relative changes in platelet and lymphocyte counts.…”

Section: Discussionmentioning

confidence: 99%

Effect of dynamic platelet-to-lymphocyte ratio on the prognosis of patients with esophageal squamous cell carcinoma receiving chemoradiotherapy

He,

Du,

et al. 2023

Medicine

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Systemic inflammatory load affects the long-term developmental outcomes in patients with malignancy. The purpose of this study was to investigate the effect of the dynamic levels of platelet-to-lymphocyte ratio (PLR) at different treatment stages on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. This study included 168 patients who received chemoradiotherapy between 2012 and 2018. PLR levels at different treatment stages were calculated based on blood test results. The association between PLR and overall survival (OS) was determined using the Kaplan–Meier method and Cox proportional regression models. The cutoff values of PLR before and after treatment of 168 patients with ESCC were 195.7 and 403.6, respectively. The 5-year OS rates of patients in the low and high pre-PLR groups were 42.1% and 21.7%, respectively. The overall 5-year OS rate of all patients was 27.1%. Multivariate analysis results showed that patient age (hazard ratio [HR] = 1.736; 95% confidence interval (CI) = 1.129–2.669; P = .012), alcohol consumption (HR = 1.622; 95%CI = 1.050–2.508; P = .029), T stage (HR = 12.483; 95%CI = 3.719–41.896; P < .001), pre-PLR (HR = 1.716; 95%CI = 1.069–2.756; P = .025), post-PLR (HR = 1.664; 95%CI = 1.106–2.503; P = .015) were independent factors of the prognosis of patients with ESCC. PLR at different treatment stages can be used to effectively evaluate the prognosis of patients with ESCC undergoing chemoradiotherapy.

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PARs in the inflammation-cancer transformation of CRC

Cited by 7 publications

References 87 publications

Differentiation and Characterization of Cystic Fibrosis Transmembrane Conductance Regulator Knockout Human Pluripotent Stem Cells into Salivary Gland Epithelial Progenitors

Differentiation and Characterization of Cystic Fibrosis Transmembrane Conductance Regulator Knockout Human Pluripotent Stem Cells into Salivary Gland Epithelial Progenitors

Integrate multiple machine learning algorithms to establish a prognostic model of risk signature for programmed cell death and hypoxia and conduct multi-omics analysis of risk signatures in colorectal cancer

Effect of dynamic platelet-to-lymphocyte ratio on the prognosis of patients with esophageal squamous cell carcinoma receiving chemoradiotherapy

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