The Diagnostic and Prognostic Significance of Serum Neutrophil Gelatinase-Associated Lipocalin Levels in Patients with Colorectal Cancer

Özemir, İbrahim Ali; Aslan, Sinan; Eren, Tunç; Bayraktar, Baris; Bilgiç, Çağrı; Isbilen, Banu; Yalman, Haydar; Yiğitbaşı, Rafet; Ali̇moğlu, Orhan

doi:10.21614/chirurgia.111.5.414

Cited by 9 publications

(7 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 33 In nonrenal, noninfectious disease, systemic inflammation likely accounts for the associations of serum NGAL with disease severity in inflammatory bowel disease 34 or metastasis of colorectal cancer. 35 For this reason, we included C-reactive protein in our multivariable models. Although the association of uNGAL with ESRD was independent of C-reactive protein in our study, we cannot exclude the possibility that systemic inflammation may contribute to elevations in uNGAL.…”

Section: Discussionmentioning

confidence: 99%

Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study

Dubin

Judd

Scherzer

et al. 2018

Kidney International Reports

View full text Add to dashboard Cite

IntroductionUrinary neutrophil gelatinase−associated lipocalin (uNGAL) and urinary kidney injury molecule−1 (uKIM-1) are established markers of subclinical acute kidney injury. In persons with reduced estimated glomerular filtration rate (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD) and death, the associations of these urinary markers with incident ESRD or death is an area of active investigation.MethodsAmong 1472 black and white participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with eGFR ≤60 ml/min per 1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine ratio (ACR) ≥30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1 with progression to ESRD and all-cause death. Cox models were sequentially adjusted for urinary creatinine, traditional risk factors, C-reactive protein, ACR, and eGFR.ResultsThere were 257 ESRD events and 819 deaths over a median follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models, higher levels of uNGAL were associated with increased risk of ESRD and death, but these associations were attenuated in fully adjusted models including baseline eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence interval [CI] 0.98–1.14) and death (HR = 1.04, 95% CI = 1.00–1.08). Higher levels of uKIM-1 were associated with increased risk of ESRD and death in demographic-adjusted models, and although attenuated in fully adjusted models, remained statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08–1.42) and death (HR = 1.10, 95% CI =1.03–1.19).ConclusionIn this cohort of high-risk patients with baseline eGFR ≤60 ml/min per 1.73 m2 and albuminuria, renal tubular injury is associated with higher mortality and progression to ESRD. Further studies are necessary to investigate the mechanism underlying this increased risk.

show abstract

Section: Discussionmentioning

confidence: 99%

Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study

Dubin

Judd

Scherzer

et al. 2018

Kidney International Reports

View full text Add to dashboard Cite

show abstract

“…Recent studies have found that serum and urine LCN2 concentrations may have diagnostic and prognostic utility in colorectal, pancreatic, and thyroid cancer. 20,43,44 Future studies using patient serum samples will be important to assess LCN2 expression and whether LCN2 can be used in conjunction with a-fetoprotein to aid in the diagnosis, surveillance, prognosis, and even therapeutic response of HB. Serum and urine LCN2 levels are also elevated in a variety of liver diseases, mirroring the progression of inflammatory and oxidative damage to the liver.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma

Molina

Bell

Tao

et al. 2018

The American Journal of Pathology

View full text Add to dashboard Cite

Hepatoblastoma (HB) is the most common pediatric liver malignant tumor. Previously, we reported co-activation of β-catenin and Yes-associated protein-1 (YAP1) in 80% of HB. Hepatic co-expression of active β-catenin and YAP1 via sleeping beauty transposon/transposase and hydrodynamic tail vein injection led to HB development in mice. Here, we identify lipocalin 2 (Lcn2) as a target of β-catenin and YAP1 in HB and show that serum Lcn2 values positively correlated with tumor burden. Lcn2 was strongly expressed in HB tumor cells in our mouse model. A tissue array of 62 HB cases showed highest LCN2 expression in embryonal and lowest in fetal, blastemal, and small cell undifferentiated forms of HB. Knockdown of LCN2 in HB cells had no effect on cell proliferation but reduced NF-κB reporter activity. Next, liver-specific Lcn2 knockout (KO) mice were generated. No difference in tumor burden was observed between Lcn2 KO mice and wild-type littermate controls after sleeping beauty transposon/transposase and hydrodynamic tail vein injection delivery of active YAP1 and β-catenin, although Lcn2 KO mice with HB lacked any serum Lcn2 elevation, demonstrating that transformed hepatocytes are the source of serum Lcn2. More blastemal areas and inflammation were observed within HB in Lcn2 KO compared with wild-type tumors. In conclusion, Lcn2 expressed in hepatocytes appears to be dispensable for the pathogenesis of HB. However, transformed hepatocytes secrete serum Lcn2, making Lcn2 a valuable biomarker for HB.

show abstract

“…NGAL appears to be a diagnostic biomarker of advanced or recurrent ovarian cancer [ 27 ] and pancreatic cancer [ 36 ]. Although serum NGAL levels increase in patients with colorectal cancer [ 30 , 31 ], NGAL does not seem to be suitable as a diagnostic biomarker [ 30 ], but can have a prognostic utility in metastatic patients [ 31 , 32 ]. NGAL levels in gastric tumor tissues are associated with worse survival [ 40 ].…”

Section: Ngal As a Biomarker In Cancermentioning

confidence: 99%

Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner?

Bauvois

Susin

2018

Cancers

View full text Add to dashboard Cite

Human neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein present in a wide variety of tissues and cell types. NGAL exists as a 25 kDa monomer, a 46 kDa homodimer (the most abundant form in healthy subjects) and a 130 kDa disulfide-linked heterodimer bound to latent matrix metalloproteinase-9. Dysregulated expression of NGAL in human malignancies suggests its value as a clinical marker. A growing body of evidence is highlighting NGAL’s paradoxical (i.e., both beneficial and detrimental) effects on cellular processes associated with tumor development (proliferation, survival, migration, invasion, and multidrug resistance). At least two distinct cell surface receptors are identified for NGAL. This review (i) summarizes our current knowledge of NGAL’s expression profiles in solid tumors and leukemias, and (ii) critically evaluates the beneficial and detrimental activities of NGAL having been documented in a diverse range of cancer-derived cell lines. A better understanding of the causal relationships between NGAL dysregulation and tumor development will require a fine analysis of the molecular aspects and biological role(s) of NGAL both in primary tumors and at different stages of disease. Having an accurate picture of NGAL’s contribution to tumor progression is a prerequisite for attempting to modulate this protein as a putative therapeutic target.

show abstract

The Diagnostic and Prognostic Significance of Serum Neutrophil Gelatinase-Associated Lipocalin Levels in Patients with Colorectal Cancer

Cited by 9 publications

References 42 publications

Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study

Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study

Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma

Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner?

Contact Info

Product

Resources

About