Circulating nuclear factor-kappa B mediates cancer-associated inflammation in human breast and colon cancer

J Med Biochem. 2021 Mar 12;40(2):150-159. doi: 10.5937/jomb0-27128.

Abstract

Background: Inflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-κB) levels as a circulating marker in the monitoring of inflammation in breast and colon cancer; to show the relationship between NF-κB with inflammatory parameters as tumour necrosis factor-α (TNF-α), soluble TNF-related apoptosis-inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels.

Methods: Serum NF-κB, TNF-α, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls.

Results: The serum NF-κB, TNF-α, IL-6, PTX-3, PCT, and serum CRP concentration was significantly higher, and the serum sTRAIL concentration was significantly lower in the patients with breast and colon cancer than in healthy controls. NF-κB was positively correlated with CRP and negatively correlated with sTRAIL.

Conclusions: These results suggest that increased NF-κB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is a relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute-phase proteins, or by abnormalities in circulating cells. NF-κB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumour, and conventional radio and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.

Uvod: Upala se smatra karakterističnim svojstvom razvoja i napredovanja raka. Cilj ovog istraživanja je bio da se ispita značaj nivoa nuklearnog faktora kapa-B (NF-kB) u serumu kao cirkulišućeg markera u praćenju upale kod karcinoma dojke i debelog creva; prikazati vezu između NF-kB i inflamatornih parametara kao što su nivoi faktora nekroze tumora-α (TNF-α), rastvorljivog liganda vezanog za TNF koji indukuje apoptozu (sTRAIL), interleukina-6 (IL-6), pentraksina-3 (PTX-3), prokalcitonina (PCT) i C-reaktivnog proteina (CRP).

Metode: Nivoi NF-kB, TNF-α, sTRAIL, IL-6, PTX-3, PCT i CRP u serumu mereni su korišćenjem imunosorbenta vezanog za enzim (ELISA) kod 40 pacijenata sa karcinomom dojke, 40 pacijenata sa karcinomom debelog creva i 30 zdravih osoba u kontrolnoj grupi.

Rezultati: Koncentracija inflamatornih parametara NF-kB, TNF, IL-6, PTX-3, PCT i CRP u serumu bila je značajno veća, a koncentracija sTRAIL u serumu bila je značajno manja kod pacijenata sa karcinomom dojke i debelog creva nego kod kontrolne grupe. NF-kB bio je u pozitivnoj korelaciji sa CRP-om i negativnoj sa sTRAIL-om.

Zaključak: Ovi rezultati sugerišu da povećani NF-kB može umanjiti kliničku efikasnost sTRAIL u čvrstim ćelijama tumora. Postoji veza između upale i karcinogeneze, tako da razvoj karcinoma počinje sa hroničnom upalom dojke i debelog creva. Rezultati istraživanja su pokazali da pacijenti sa karcinomom debelog creva i dojke imaju pojačanu sistemsku upalu, merenu povećanim cirkulišućim citokinima i proteinima akutne faze, ili abnormalnostima u cirkulišućim ćelijama. NF-kB se može kombinovati sa drugim markerima sistemskog inflamatornog odgovora u prognostičkim procenama raka. Pored hirurške resekcije tumora, konvencionalne radioterapije i hemoterapije za lečenje raka, upotreba sTRAIL ili drugih agonista za terapiju raka pojavila se kao nova potencijalna terapija.

Keywords: interleukin-6; nuclear factor kappa-B; pentraxin-3; soluble TNF-related apoptosis-inducing ligand; tumour necrosis factor-α.