Lipocalin 2—not only a biomarker: a study of current literature and systematic findings of ongoing clinical trials

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Abstract

Lipocalin 2 (Lcn2), also known as neutrophil gelatinase–associated lipocalin, is an innate immune protein encoded by the LCN2 gene. In this study, we investigated various roles and functions of Lcn2 characterized in a systems-based format and evaluated its therapeutic potentials and clinical relevance for diagnosis and prognosis. An additional systematic presentation was presented for 70 ongoing clinical trials utilizing Lcn2 in the diagnostic and prognostic setting as a key outcome measure. With trials being conducted through December 2030, Lcn2 will become all the more relevant given its associations with diseases as a prognostic biomarker. Data also suggests that it plays a role in pathological conditions. The gaps in our understanding of Lcn2, once filled, may improve the immune mediation of acute and chronic disease.

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Ovarian cancer statistics, 2018

Lindsey A Torre, Britton Trabert, Carol DeSantis … (2018)

In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.

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Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.

Trude Flo, Kelly D. Smith, Shintaro Sato … (2004)

Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.

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Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

Manu Shankar-Hari, Gary Phillips, Mitchell Levy … (2016)

Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition.

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Author and article information

Contributors

Azza Sarfraz:

ORCID: http://orcid.org/0000-0001-8206-5745

azza.sarfraz@aku.edu

Journal

Journal ID (nlm-ta): Immunol Res

Journal ID (iso-abbrev): Immunol Res

Title: Immunologic Research

Publisher: Springer US (New York )

ISSN (Print): 0257-277X

ISSN (Electronic): 1559-0755

Publication date (Electronic): 19 December 2022

Pages: 1-27

Affiliations

[1 ]Sargodha Medical College, Sargodha, Pakistan

[2 ]GRID grid.414774.5, ISNI 0000 0000 9694 4612, Fatima Jinnah Medical University, ; Lahore, Pakistan

[3 ]Azra Naheed Medical College, Lahore, Pakistan

[4 ]GRID grid.7147.5, ISNI 0000 0001 0633 6224, The Aga Khan University, ; Karachi, Pakistan

[5 ]GRID grid.7147.5, ISNI 0000 0001 0633 6224, Department of Pediatrics and Child Health, , Aga Khan University, ; Stadium Road, P.O Box 3500, Karachi, 74800 Pakistan

[6 ]GRID grid.442156.0, ISNI 0000 0000 9557 7590, Universidad Espíritu Santo, ; Samborondón, Ecuador

Author information

Azza Sarfraz http://orcid.org/0000-0001-8206-5745

Article

Publisher ID: 9352

DOI: 10.1007/s12026-022-09352-2

PMC ID: 9760530

PubMed ID: 36529828

SO-VID: 4c24ba68-bf11-420f-97a1-082e93af1aa9

Copyright © © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Lipocalin 2—not only a biomarker: a study of current literature and systematic findings of ongoing clinical trials

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Karger: Coronavirus / COVID-19

Most cited references 58

Ovarian cancer statistics, 2018

Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

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