Can NGAL be Employed as Prognostic and Diagnostic Biomarker in Human Cancers? A Systematic Review of Current Evidence

Rovedatti, L.; Pecoraro, Valentina; Trenti, Tommaso

doi:10.5301/jbm.5000245

Cited by 38 publications

(28 citation statements)

References 53 publications

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“…We and others previously showed that Lcn2 levels are significantly up-regulated in tissues and urine samples from patients with invasive breast cancer (25,(27)(28)(29)(30). We further confirmed that Lcn2 gene expression was significantly up-regulated in human TNBC cell lines (MDA-MB-231 and MDA-MB-436) in comparison with nonneoplastic MCF10A cells (Fig.…”

Section: Deformable Tnlgs Breach In Vitro Tumor Endothelial Barrier Vsupporting

confidence: 84%

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Guo

Yang

Huang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Triple-negative breast cancer (TNBC), which has the highest mortality rate of all breast cancer, is in urgent need of a therapeutic that hinders the spread and growth of cancer cells. CRISPR genome editing holds the promise of a potential cure for many genetic diseases, including TNBC; however, its clinical translation is being challenged by the lack of safe and effective nonviral delivery systems for in vivo therapeutic genome editing. Here we report the synthesis and application of a noncationic, deformable, and tumor-targeted nanolipogel system (tNLG) for CRISPR genome editing in TNBC tumors. We have demonstrated that tNLGs mediate a potent CRISPR knockout of Lipocalin 2 (Lcn2), a known breast cancer oncogene, in human TNBC cells in vitro and in vivo. The loss of Lcn2 significantly inhibits the migration and the mesenchymal phenotype of human TNBC cells and subsequently attenuates TNBC aggressiveness. In an orthotopic TNBC model, we have shown that systemically administered tNLGs mediated >81% CRISPR knockout of Lcn2 in TNBC tumor tissues, resulting in significant tumor growth suppression (>77%). Our proof-of-principle results provide experimental evidence that tNLGs can be used as a safe, precise, and effective delivery approach for in vivo CRISPR genome editing in TNBC.

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Section: Deformable Tnlgs Breach In Vitro Tumor Endothelial Barrier Vsupporting

confidence: 84%

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Guo

Yang

Huang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…NGAL is not useful for diagnosing renal cell carcinoma [ 37 ], but it may be helpful to select a proper therapy in cases of metastatic disease without the need for pretreatment biopsy [ 38 ]. Interestingly, Roli et al recently reevaluated the potential value of NGAL as a prognostic and diagnostic marker in cancer [ 47 ]. Their meta-analysis shows that high NGAL levels in biological fluids, such as serum and urine, could be useful to predict disease-free survival for patients with colorectal and breast cancer, but its prognostic and diagnostic accuracy remains uncertain for other human tumors, including pancreatic, thyroid, liver, lung, esophageal, oral, and kidney tumors [ 47 ].…”

Section: Ngal As a Biomarker In Cancermentioning

confidence: 99%

“…Interestingly, Roli et al recently reevaluated the potential value of NGAL as a prognostic and diagnostic marker in cancer [ 47 ]. Their meta-analysis shows that high NGAL levels in biological fluids, such as serum and urine, could be useful to predict disease-free survival for patients with colorectal and breast cancer, but its prognostic and diagnostic accuracy remains uncertain for other human tumors, including pancreatic, thyroid, liver, lung, esophageal, oral, and kidney tumors [ 47 ]. Note that in the cancers evaluated, the inclusion of single studies enrolling a limited number of patients influence the results by overestimating the effect size [ 47 ].…”

Section: Ngal As a Biomarker In Cancermentioning

confidence: 99%

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

Bauvois

Susin

2018

Cancers

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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.

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“…Transcripts of LCN2 were significantly higher in the majority of solid tumors including PDAC when compared to normal tissues [ 29 ]. A recent review stated that the discriminative power of LCN2 between PDAC patients and controls was acceptable, but the diagnostic accuracy remained uncertain [ 30 ]. LCN2 discriminated between PDAC and CP [ 24 , 29 , 31 ] with limited accuracy and was eliminated from validation tests by some groups [ 24 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer

Bartsch

Gercke

Strauch³

et al. 2018

JCM

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Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates for screening. Unfortunately, neither reliable imaging modalities nor biomarkers are available to detect high-grade precursor lesions or early cancer. Circulating levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma (PDAC, n = 50), FPC (n = 20), chronic pancreatitis (n = 10), IAR with relevant precursor lesions (n = 11) or non-relevant lesions (n = 5), 20 controls, and IAR with (n = 51) or without (n = 51) lesions on pancreatic imaging. In addition, corresponding duodenal juice samples were analyzed for Glypican-1 (n = 144) enrichment and KRAS mutations (n = 123). The panel miR-196b/LCN2/TIMP1 could distinguish high-grade lesions and stage I PDAC from controls with absolute specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes and duodenal juice was not diagnostic. KRAS mutations in duodenal juice were detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1 levels (p = 0.0007) and KRAS mutations in duodenal juice (p = 0.0004) significantly more often than IAR without imaging lesions. The combination miR-196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high-grade PDAC precursor lesions in IAR of FPC families.

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Can NGAL be Employed as Prognostic and Diagnostic Biomarker in Human Cancers? A Systematic Review of Current Evidence

Abstract: NGAL determination in plasma and urine could be useful in the prognosis of colorectal and breast cancer, but its prognostic accuracy remains uncertain for other human tumors.

Cited by 38 publications

References 53 publications

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

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

The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer

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