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Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps

Johdi NA, Mazlan L, Sagap I, Jamal R

Cytokine, 2017 11;99:35-42.
PMID: 28689023 DOI: 10.1016/j.cyto.2017.06.015

Soluble proteins including cytokines, chemokines and growth factors are small proteins that mediate and regulate immunity. They involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these soluble proteins may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many these soluble proteins simultaneously, thus allowing rapid, cost effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines, chemokines and other soluble proteins from the serum derived from colorectal carcinoma (CRC, n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these soluble proteins can classify these groups of populations and explore the possible application of the soluble proteins as biomarkers in early stage screening and/or surveillance. We observed significant high IL-4, MIP-1β, FasL and TGF-β1 levels but lower levels for RANTES in P-derived serum as compared to N-derived serum. Significant high IL-8, VEGF, MIP-1β, Eotaxin and G-CSF observed in CRC-derived serum when compared to N-derived serum. Between CRC- and P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower levels for TGF-β1 were detected in CRC-derived serum. These preliminary results were obtained from small sample size and could be further validated with larger sample size cohort to produce a panel of biomarkers for CRC and P patients. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.

Matched MeSH terms: Chemokines/blood*
Fulltext Adipocyte-Specific Fatty Acid-Binding Protein (AFABP) and Chemerin in Association with Gestational Diabetes: A Case-Control Study

Mosavat M, Mirsanjari M, Lwaleed BA, Kamarudin M, Omar SZ

J Diabetes Res, 2021;2021:5533802.
PMID: 34007846 DOI: 10.1155/2021/5533802

BACKGROUND: Adipocytokines participate in regulating the inflammatory response in glucose homeostasis and type 2 diabetes. However, among these peptides, the role of adipocyte-specific fatty-acid-binding protein (AFABP), chemerin, and secreted protein acidic and rich in cysteine (SPARC) in gestational diabetes (GDM) has not been fully investigated.
METHOD: The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24-28 weeks, before delivery, immediate postpartum, and 2-6 months postpuerperium.
RESULTS: Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 (r = 0.50), insulin resistance index (r = 0.26), and body mass index (r = 0.28) and inversely correlated to C-reactive protein (r = -0.27). Chemerin levels were directly and strongly correlated with IL-10 (r = 0.41) and interleukin-4 (r = 0.50) and inversely correlated to insulin resistance index (r = -0.23) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups.
CONCLUSION: AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.

Matched MeSH terms: Chemokines/blood*
Fulltext Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization

Liew YK, Awang Hamat R, van Belkum A, Chong PP, Neela V

Clin Vaccine Immunol, 2015 May;22(5):593-603.
PMID: 25809633 DOI: 10.1128/CVI.00493-14

The exoproteome of Staphylococcus aureus contains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three different S. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios included S. aureus bacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, an N-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers.

Matched MeSH terms: Chemokines/blood

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