LCN2 as a Potential Diagnostic Biomarker for Ulcerative Colitis-Associated Carcinogenesis Related to Disease Duration

Kou, Fushun; Cheng, Yuan; Shi, Lei; Liu, Jiajing; Liu, Yuyue; Shi, Rui; Peng, Guiying; Li, Junxiang

doi:10.3389/fonc.2021.793760

Cited by 15 publications

(15 citation statements)

References 47 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipocalin-2 (LCN2) is a secreted glycoprotein and belongs to the lipocalin superfamily, containing multiple kinds of cells, myeloid cells, and intestinal epithelial cells. This is relevant to inflammatory bowel disease (50). LCN2 can be triggered by diverse proinflammatory stimuli, IL-1 and IL-22, and the activation of Toll-like receptors (51), and a large amount can be released into the gut lumen (52).…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Qian¹,

Tang²,

Ouyang³

et al. 2023

Ann Transl Med

View full text Add to dashboard Cite

Background: Ulcerative colitis (UC) is an idiopathic, chronic disorder characterized by inflammation, injury, and disruption of the colonic mucosa. However, there are still many difficulties in the diagnosis and differential diagnosis of UC. An increasing amount of research has shown a connection between ferroptosis and the etiology of UC. Therefore, our study aimed to identify the key genes related to ferroptosis in UC to provide new ideas for diagnosis UC.Methods: Gene expression profiles of normal and UC samples were extracted from the Gene Expression Omnibus (GEO) database. By combining differentially expressed genes (DEGs), Weighted correlation network analysis (WGCNA) genes, and ferroptosis-related genes, hub genes were identified and then screened using Lasso regression. Based on the key genes, gene ontology (GO) and gene set enrichment analysis (GSEA) analyses were performed. We used NaiveBeyas, Logistic, IBk, and RandomForest algorithms to build a disease diagnosis model using the hub genes. The model was validated using GSE87473 as the validation set.Results: Gene expression matrices of GSE87466 and GSE75214 were downloaded from the GEO database, including 184 UC patients and 43 control samples. A total of 699 DEGs were obtained. From FerrDb, 565 genes related to ferroptosis were identified. The 1,513 genes with the highest absolute correlation coefficient value in the MEblue module were obtained from WGCNA analysis. Five hub genes (LCN2, MUC1, PARP8, PLIN2, and TIMP1) were identified using the Lasso regression algorithm based on the overlapped DEGs, WGCNA-identified genes, and ferroptosis-related genes. GO and GSEA analyses revealed that 5 hub genes were identified as being involved in the negative regulation of transcription by competitive promoter binding, cellular response to citrate cycle_tca_cycle, cytosolic_dna_sensing pathway, UV-A, and beta-alanine metabolism. The logistic algorithm's values of the area under the curve (AUC)were 1.000 and 0.995 for training and validation cohorts, and sensitivity is 0.962, specificity is 1.000, respectively, as determined by comparing various methods. Conclusions:The previously described hub genes were identified as being intimately related to ferroptosis in UC and capable of distinguishing UC patients from controls. By detecting the expression of several genes, this model may aid in diagnosing UC and understanding the etiology and treatment of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Qian¹,

Tang²,

Ouyang³

et al. 2023

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…The 34 selected records explored 17 different biomarkers (Figure 1), including 9 molecules from the granules [21][22][23][24][25][26][27][28][29][30][31][32][33][34] ; 2 found in the cytoplasm, 27,[35][36][37][38][39] 2 in the plasmatic membrane, 31,32,[40][41][42][43][44][45][46][47][48] and 4 only formed in the plasma. 25,32,43,46,[49][50][51][52][53][54] The most mentioned biomarker was nCD64 (index or ratio; 7 times), 31,[40][41][42][43][44][45] followed by calprotectin (5 times) 27,…”

Section: Neutrophil Biomarkersmentioning

confidence: 99%

“…Eight studies involved pediatric populations (n = 338). 28,[39][40][41][42][43][44][45] Of the 34 selected studies, 19 had key endpoints based on disease activity, 21-23,26-29,31,35,38,39,41,43-45, 48-50,52 8 on endoscopic response/mucosal healing, 25,32,34,38,46,50,53,54 8 on treatment-related endpoints, 29,33,37,40,42,43,45,51 7 on clinical manifestations and/or complications, 24,29,30,33,36,47,26 and 3 on biochemical response (all FC-based definitions). 31,41,42 In total, 19 studies focused exclusively on patients taking infliximab (IFX) and/or adalimumab (ADA), 22,23,25,27,30,31,34,35,[39][40][41]43,[45]…”

Section: Neutrophil Biomarkersmentioning

confidence: 99%

“…23 In a gene expression study, NGAL serum expression was identified as a proxy of disease duration in UC, which, in turn, correlates with the risk of UC-associated carcinogenesis (UCAC), suggesting NGAL might be a useful early predictor and risk monitoring biomarker of UCAC. 24 LL-37 (cathelicidin) and chitinase 3-like 1 (also known as YKL-40) were evaluated in the same retrospective cohort of 176 UC patients, which did not find differences in pre-anti-TNFα levels between future mucosal healers and non-healers. 25 However, in a double-cohort study including 80 UC and 95 CD patients, elevated LL-37 serum levels predicted higher improvement in clinical activity after 6-18 months in UC and CD patients with moderate-severe disease activity, whereas low LL-37 levels predicted intestinal strictures in CD.…”

Section: Therapeutic Advances In Gastroenterologymentioning

confidence: 99%

See 1 more Smart Citation

Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease

Magalhães

Peyrin–Biroulet

Estevinho

et al. 2023

Therap Adv Gastroenterol

View full text Add to dashboard Cite

Background: Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages. Objective: To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD. Design: Systematic scoping review. Data sources and methods: We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included. Results: From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn’s disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase–associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior. Conclusion: Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker. Registration: https://osf.io/kes9a .

show abstract

“…Then, the fecal sample comes into direct contact with the inflamed gut, so the concentration of fecal biomarkers should better reflect the degree and severity of inflammation than other markers . In recent years, several fecal markers have been reported in the diagnosis and monitoring of IBD, such as matrix metalloproteinase 9 (MMP 9), calprotectin, lactoferrin, , lipocalin 2, , alkaline phosphatase, etc.…”

Section: Introductionmentioning

confidence: 99%

Biosensing Intestinal Alkaline Phosphatase by Pregnancy Test Strips Based on Target-Triggered CRISPR-Cas12a Activity to Monitor Intestinal Inflammation

Jia,

Zhang,

Zhang

et al. 2023

Anal. Chem.

View full text Add to dashboard Cite

With an increasing incidence worldwide, inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, which impairs the life quality of patients. Therefore, it is of great significance to construct a sensitive, simple, and convenient biosensor to analyze IBDassociated biomarkers for an auxiliary diagnosis of IBD. Intestinal alkaline phosphatase (IAP), expressed by the intestinal epithelium, is an endogenous protein that is thought to play a vital role in maintaining intestinal homeostasis and is considered a potential biomarker for IBD. Here, an IAP detection method was developed using pregnancy test strips by dephosphorylation. Initially, a double-stranded DNA (dsDNA) was designed to respond to IAP and acted as an activator of Cas12a. In the presence of IAP, the designed dsDNA was not digested by lambda exonuclease (λ exo), which hybridized to the Cas12a-crRNA duplex and resulted in the activation of the trans-cleavage of Cas12a. Further, the activated Cas12a cleaved the single-strand DNA (ssDNA) linker in the MBs-ssDNA-hCG probe, triggering the release of hCG. With magnetic separation, the released hCG could be quantitatively detected by pregnancy test strips. IAP levels were analyzed in feces from colitis and healthy mice by pregnancy test strips. The results showed that the IAP level of colitis mice (3.89 ± 1.92 U/L) was much lower than that of healthy mice (39.64 ± 24.93 U/L), indicating the correlation between IAP and intestinal inflammation. Taken together, a sensitive, user-friendly detection assay based on pregnancy test strips was constructed to monitor IAP and used as an auxiliary diagnostic approach for IBD in a clinical scene.

show abstract

LCN2 as a Potential Diagnostic Biomarker for Ulcerative Colitis-Associated Carcinogenesis Related to Disease Duration

Cited by 15 publications

References 47 publications

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease

Biosensing Intestinal Alkaline Phosphatase by Pregnancy Test Strips Based on Target-Triggered CRISPR-Cas12a Activity to Monitor Intestinal Inflammation

Contact Info

Product

Resources

About