Stanniocalcin 1 is a serum biomarker and potential therapeutic target for <scp>HBV</scp>‐associated liver fibrosis

Chan, Kristy Kwan‐Shuen; Hon, Tsz-Chun; Au, Kin Pan; Choi, H.L.; Wong, Danny Ka‐Ho; Chan, Albert Chi‐Yan; Yuen, Man-Fung; Lai, Ching–Lung; Lo, Ronald

doi:10.1002/path.5880

Cited by 12 publications

(8 citation statements)

References 50 publications

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“…Genes represented in our TRS include five members predicted to be secreted proteins according to The Human Protein Atlas (https://www.proteinatlas.org), which could be explored further in suitably well-annotated clinical samples. Although not previously reported in NAFLD, CHRDL2 is upregulated in a range of tumour tissues including HCC 43 , while STC1, CTGF 44 , GDNF and FGF7 are all linked to hepatic fibrogenesis 45,46 . Additionally, STC1 is a potential serum biomarker for hepatitis B virus-associated liver fibrosis 45 and secreted FGF7 47 may be a prognostic marker in cholangiocarcinoma.…”

Section: Discussionmentioning

confidence: 69%

“…Although not previously reported in NAFLD, CHRDL2 is upregulated in a range of tumour tissues including HCC 43 , while STC1, CTGF 44 , GDNF and FGF7 are all linked to hepatic fibrogenesis 45,46 . Additionally, STC1 is a potential serum biomarker for hepatitis B virus-associated liver fibrosis 45 and secreted FGF7 47 may be a prognostic marker in cholangiocarcinoma. The predictive model requires external validation, ideally in prospective longitudinal studies.…”

Section: Discussionmentioning

confidence: 69%

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SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

Fallowfield

Kendall

Jimenez-Ramos

et al. 2023

Preprint

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Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide and a growing healthcare burden. The pathobiology of NAFLD is complex, disease progression is variable and unpredictable, and there are no qualified prognostic biomarkers or licensed pharmacotherapies that can improve clinical outcomes; it represents an unmet precision medicine challenge. We established a retrospective multicentre national cohort of 940 patients, across the complete NAFLD spectrum, integrating quantitative digital pathology, hepatic RNA-sequencing and 5.67 million days of longitudinal electronic health record follow-up into a secure, searchable, open resource (SteatoSITE) to inform rational biomarker and drug development and facilitate personalised medicine approaches for NAFLD. A complementary web-based gene browser was also developed. Here, our initial analysis uncovers disease stage-specific gene expression signatures, pathogenic hepatic cell subpopulations and master regulator networks associated with disease progression in NAFLD. Additionally, we construct novel transcriptional risk prediction tools for the development of future hepatic decompensation events.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 69%

SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

Fallowfield

Kendall

Jimenez-Ramos

et al. 2023

Preprint

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“…Genes preferentially or specifically dysregulated by CCl 4 in the fibroblast subpopulation include a 174-fold induction of Sectm1a, which stabilizes tissue resident macrophages in response to acute inflammation 103 , and a 160-fold suppression of Nkx6-1, an unfavorable prognostic marker for human hepatocellular carcinoma 104 . Genes specifically dysregulated in VSMCs include Stc1, a classic inflammation marker in fibrotic disease 105 , as well as lnc24481*, which was up regulated 16-fold, and lnc43318, which was 5- fold down regulated by CCl 4 exposure. HSCs showed the most extensive dysregulation, impacting 1,296 genes (743 PCGs, 553 lncRNAs lncRNAs), >90% of which were specifically dysregulated in HSCs (Table S6A).…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of murine long non-coding single cell transcriptome in non-alcoholic steatohepatitis and liver fibrosis

Karri

Waxman

2022

Preprint

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LncRNAs are typified by low expression, nuclear enrichment, high tissue-specificity and functional diversity, but the vast majority are uncharacterized. Here, we develop a catalog of 48,000 mouse liver-expressed lncRNAs and use to elucidate lncRNA dysregulation in high fat diet-induced non-alcoholic steatohepatitis and carbon tetrachloride-induced liver fibrosis by single cell RNA-seq. LncRNA zonation patterns across the liver lobule were discovered in five cell populations. Perturbations in lncRNA expression were common in disease-associated cell types, including non-alcoholic steatohepatitis-associated macrophages, a hallmark of fatty liver disease progression, and collagen-producing myofibroblasts, key to liver fibrosis. Gene regulatory network analysis linked individual lncRNAs to biological pathways and network centrality metrics identified network-essential, disease-associated regulatory lncRNAs. Regulatory lncRNAs with network-predicted target gene promoters enriched for triplex-based lncRNA binding were also identified. These findings elucidate hepatic lncRNA cell-type specificities, spatial zonation patterns, linked biological networks and dysregulation in disease progression. A subset of the disease-associated lncRNAs have human orthologs and are promising candidates for biomarkers and therapeutic targets.

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“… 27 Previous reports revealed roles of STC1 in fibrosis of the kidney, 28 lung 29 and liver. 30 Additionally, the MMP family is devoted to maintaining ECM homeostasis and collagen formation, which is important for endometriosis fibrosis, suggesting a vital role of MMP1 in AM development. 31 We also found that a variety of collagen associated genes were highly expressed in fibroblasts, including FBLN1 and LUM .…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Profiling Uncovers the Roles of Endometrial Fibrosis and Microenvironmental Changes in Adenomyosis

Niu,

Zhang,

Liu

et al. 2023

JIR

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Purpose Adenomyosis (AM) is a common benign uterine disorder that has deleterious effects on women’s health. However, the pathogenesis of AM is not clearly understood. We aimed to investigate the pathophysiological changes and molecular mechanism in AM. Methods Single-cell RNA sequencing (scRNA-seq) was employed to construct a transcriptomic atlas of various cell subsets from the ectopic endometrium (EC) and eutopic endometrium (EM) of one AM patient and evaluate differential expression. The Cell Ranger software pipeline (version 4.0.0) was applied to conduct sample demultiplexing, barcode processing and mapping reads to the reference genome (human GRCh38). Different cell types were classified with markers with the “FindAllMarkers” function, and differential gene expression analysis was performed with Seurat software in R. The findings were confirmed by Reverse Transcription Real-Time PCR using samples from three AM patients. Results We identified nine cell types: endothelial cells, epithelial cells, myoepithelial cells, smooth muscle cells, fibroblasts, lymphocytes, mast cells, macrophages and unknown cells. A number of differentially expressed genes, including CLO4A1, MMP1, TPM2 and CXCL8 , were identified from all cell types. Functional enrichment showed that aberrant gene expression in fibroblasts and immune cells was related to fibrosis-associated terms, such as extracellular matrix dysregulation, focal adhesion and the PI3K-Akt signaling pathway. We also identified fibroblast subtypes and determined a potential developmental trajectory related to AM. In addition, we identified increased cell–cell communication patterns in EC, highlighting the imbalanced microenvironment in AM progression. Conclusion Our results support the theory of endometrial–myometrial interface disruption for AM, and repeated tissue injury and repair could lead to increased fibrosis in the endometrium. Therefore, the present study reveals the association between fibrosis, the microenvironment, and AM pathogenesis. This study provides insight into the molecular mechanisms regulating AM progression.

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Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Cited by 12 publications

References 50 publications

SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

Dysregulation of murine long non-coding single cell transcriptome in non-alcoholic steatohepatitis and liver fibrosis

Single-Cell Profiling Uncovers the Roles of Endometrial Fibrosis and Microenvironmental Changes in Adenomyosis

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