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. 2022 Feb 2;41(1):79-90.
doi: 10.5937/jomb0-30135.

Anemia of inflammation in patients with colorectal cancer: Correlation with interleukin-1, interleukin-33 and galectin-1

Miodrag Jocić  1 , Nebojša Arsenijević  2 , Nevena Gajović  2 , Milena Jurišević  3 , Ivan Jovanović  2 , Milan Jovanović  4 , Nataša Zdravković  5 , Veljko Marić  6 , Marina Jovanović  5
Affiliations

Anemia of inflammation in patients with colorectal cancer: Correlation with interleukin-1, interleukin-33 and galectin-1

Miodrag Jocić et al. J Med Biochem. .

Abstract
in English, Serbian

Background: Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients.

Methods: Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia).

Results: CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients.

Conclusions: Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

Uvod: Pacijenti sa kolorektalnim karcinomom (CRC) imaju anemiju koja je često prisutna kao posledica hroničnog krvarenja iz tumora. Tačna uloga IL-33, galektin-1 i IL-1 u patološkoj genezi anemije kod pacijenata sa kolorektalnim karcinomom još nije razjašnjena. Glavni cilj ovog istraživanja bio je analiza sistemskih vrednosti Gal-1, IL-1 i lL-33 kod anemičnih i neanemičnih CRC pacijenata.

Metode: Koncentracije IL-33, galektin-1 i IL-1 ispitivane su u uzorcima krvi 55 pacijenata sa CRC (27 bez anemije i 28 sa anemijom).

Rezultati: CRC pacijenti sa anemijom imali su težu i lokalno uznapredovalu bolest u poređenju sa CRC neanemičnim pacijentima. Anemija je pozitivno korelirala sa višom nuklearnom invazijom, invazijom limfe i krvnih sudova, kao i sa višim TNM stadijumom, uočljivim metastatskim lezijama u plućima i jetri i peritonealnoj karcinomatozi. Značajno veće koncentracije IL-33, Gal-1 i IL-1 pronađene su u serumima pacijenata sa CRC i otkrivenom anemijom. CRC pacijenti su uglavnom imali mikrocitnu anemiju, dok su vrednosti feritina bile u normalnom opsegu. Analiza je otkrila pozitivnu međusobnu korelaciju između serumskih vrednosti galektina-1, IL-1 i IL-33 kod pacijenata sa CRC. Nivo hemoglobina u negativnoj korelaciji sa serumskim IL-33, Gal-1 i IL-1. Analizirali smo ROC krive seruma IL-33, Gal-1 i IL-1 što je ukazalo da se ovi citokini mogu tretirati kao dodatni markeri za anemiju upale kod pacijenata sa CRC.

Zaključak: Predominacija galektin-1, IL-1 i IL-33 kod anemičnih CRC pacijenata implicira na njihovu potencijalnu ulogu u nastanku anemije i daljem razvoju.

Keywords: Anemia; Colorectal carcinoma; Gal-1; IL-1; IL-33.

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Conflict of interest statement

Conflict of Interest: The authors stated that they have no conflicts of interest regarding the publication of this article.

Figures

Figure 1
Figure 1. CRC patients with anemia have severe and local advanced disease
A. Patients with CRC and anemia had higher nucleargrade of colorectal cancer
B. Higher percentage of blood vessels invasion or
C. lymph vessels invasion in comparison to CRC patients without anemia
Chi-Square test was used (* p < 0.05; ** p < 0.01)
Figure 2
Figure 2. Anemia correlates with more progressive form of CRC
A. Patients with CRC and anemia had significantly advancedTNM stage
B. higher percentage of detectable metastatic lesions in liver
C. lung or
D. peritoneal carcinomatosis compared to CRC patients without anemia
Chi-Square test was used (* p < 0.05; ** p < 0.01)
Figure 3
Figure 3
A, B, C Anemic CRC patients had higher concentration of IL-33, Gal-1 and IL-1 b in serum compared to non-anemic CRC patients
D. Positive correlation between galectin-1 and IL-33, galectin-1 and IL-1 and IL-33 and IL-1 values in serum of CRC patients
Correlation was determined using Spearman’s test (* p< 0.05; ** p< 0.01)
Figure 4
Figure 4
A Significantly lower MCV of red blood cells in anemic CRC patient
B, C, D. Significantly higher IL-1, Gal-1 and IL-1β in serum of CRC patients with microcytic anemia in comparison to CRC patients with normocytic anemia or without anemia
E,F, G.Strong positive correlation was detected between galectin-1 and IL-33, galectin-1 and IL-1 β and IL-33 and IL-1 β, valuesin serum of CRC patients with diagnosed microcytic anemia
Correlation was determined using Spearman’s test (* p < 0.05; **p < 0.01)
Figure 5
Figure 5
A Patients with CRC and anemia had significantlyhigher number of platelets compared to non-anemic patientswith CRC
B. Positive correlation between thrombocytosisand IL-33, Gal-1 and IL-1 b, respectively. Correlation wasdetermined using Spearman’s test (* p < 0.05; ** p < 0.01)
Figure 6
Figure 6
A Moderate negative correlation between serum hemoglobin level and IL-33, Gal-1 and IL-1 b, respectively
B. Specificity and sensitivity of IL-33, Gal-1 and IL-1 in serum
Correlation was determined using Spearman’s test (* p < 0.05;** p < 0.01)
Figure 7
Figure 7. Potential synergistic effect of IL-1 and IL-33 in pathogenesis of anemia of inflammation in CRC patients
1. IL-1 and IL-33 directly inhibit erythropoiesis and disable synthesis of hemoglobin via suppression of iron utilization
2. Gal-1 and IL-33 activate NF-kB transcriptional factor and indirectly stimulate proinflammatory cytokines production, such as IL-1 production, which then inhibits erythropoiesis. In turn subsequent anemia correlates with severe and more progressive CRC
(*Created by the authors with BioRender.com)
See this image and copyright information in PMC

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