SMAD7 and SERPINE1 as novel dynamic network biomarkers detect and regulate the tipping point of TGF-beta induced EMT

Jiang, Zhenfei; Lu, Lina; Liu, Yuwei; Zhang, Si; Li, Shuxian; Wang, Guanyu; Wang, Peng; Chen, Luonan

doi:10.1016/j.scib.2020.01.013

Cited by 20 publications

(11 citation statements)

References 76 publications

(88 reference statements)

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“…There are critical transitions during the EMT process, which is prevalent in paraneoplastic tissues. 31 As the adjacent colorectal tissue is also in the transitional state of the tumor tissue, we suggest a critical transition in the immune activity of mature B cells during early tumor progression, a period that facilitates early intervention.…”

Section: Discussionmentioning

confidence: 76%

“… 28 The metastasis of CRC is preceded by a transitional phase characterized by dramatic changes in the immune activity of B cells, which play an important role in the metastasis of CRC. 29 To quantify this process, we applied dynamic network biomarkers (DNBs) 29 , 30 , 31 to predict the tipping point for CRC metastasis. DNBs are a group of strongly correlated and fluctuating molecules used for disease prediction or as an early warning.…”

Section: Introductionmentioning

confidence: 99%

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Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

Liu

Zhong

et al. 2021

Molecular Therapy - Oncolytics

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Increasing evidence indicates that mature B cells in the adjacent tumor tissue, both as an intermediate state, are vital in advanced colorectal cancer (CRC), which is associated with a low survival rate. Developing predictive biomarkers that detect the tipping point of mature B cells before lymph node metastasis in CRC is critical to prevent irreversible deterioration. We analyzed B cells in the adjacent tissues of CRC samples from different stages using the dynamic network biomarker (DNB) method. Single-cell profiling of 725 CRC-derived B cells revealed the emergence of a mature B cell subtype. Using the DNB method, we identified stage II as a critical period before lymph node metastasis and that reversed difference genes triggered by DNBs were enriched in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway involving B cell immune capability. DHX9 (DEAH-box helicase 9) was a specific para-cancerous tissue DNB key gene. The dynamic expression levels of DHX9 and its proximate network genes involved in B cell-related pathways were reversed at the network level from stage I to III. In summary, DHX9 in mature B cells of CRC-adjacent tissues may serve as a predictable biomarker and a potential immune target in CRC progression.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

Liu

Zhong

et al. 2021

Molecular Therapy - Oncolytics

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“…The intersection of these DNB genes and TP-DEGs (or TP-DNGs) was taken as candidate DNB genes. And the core DNB genes and candidate DNB genes reflected the layer composition of DNB genes on the network ( Liu et al, 2012 ; Jiang et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Landscape dynamic network biomarker analysis reveals the tipping point of transcriptome reprogramming to prevent skin photodamage

Zhang

et al. 2021

Journal of Molecular Cell Biology

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Skin, as the outmost layer of human body, is frequently exposed to environmental stressors including pollutants and ultraviolet (UV), which could lead to skin disorders. Generally, skin response process to ultraviolet B (UVB) irradiation is a nonlinear dynamic process, with unknown underlying molecular mechanism of critical transition. Here, the landscape dynamic network biomarker (l-DNB) analysis of time series transcriptome data on 3D skin model was conducted to reveal the complicated process of skin response to UV irradiation at both molecular and network levels. The advanced l-DNB analysis approach showed that: (i) there was a tipping point before critical transition state during pigmentation process, validated by 3D skin model; (ii) 13 core DNB genes were identified to detect the tipping point as a network biomarker, supported by computational assessment; (iii) core DNB genes such as COL7A1 and CTNNB1 can effectively predict skin lightening, validated by independent human skin data. Overall, this study provides new insights for skin response to repetitive UVB irradiation, including dynamic pathway pattern, bi-phasic response, and DNBs for skin lightening change, and enables us to further understand the skin resilience process after external stress.

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“…For example, early warning signals of lung metastasis have been found in liver cancer, and with the help of time-series gene expression data in spontaneous lung metastasis mouse models, it was determined that the calcium ion conductive protein gene (Calmodulin-like-protein 3, CALML3) is significantly related to the initiation of metastasis, and it was confirmed that knocking down CALML3 can inhibit metastasis [37] . Zhang et al identified a premalignant state of gallbladder cancer using the DNB method by integrating single-cell information [38] . The combination of DNBs with pseudotime analysis enables a more precise determination of cell subtypes where some subtypes are mixed.…”

Section: Application Of Dnbs For the Detection Of Tipping Points And ...mentioning

confidence: 99%

Development of a dynamic network biomarkers method and its application for detecting the tipping point of prior disease development

Han

Zhong

et al. 2022

Computational and Structural Biotechnology Journal

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SMAD7 and SERPINE1 as novel dynamic network biomarkers detect and regulate the tipping point of TGF-beta induced EMT

Cited by 20 publications

References 76 publications

Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

Landscape dynamic network biomarker analysis reveals the tipping point of transcriptome reprogramming to prevent skin photodamage

Development of a dynamic network biomarkers method and its application for detecting the tipping point of prior disease development

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