Preliminary analysis of single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes and profile of circulating cytokines in patients with gastric Cancer

Abstract

BackgroundGastric Cancer is highly prevalent and deadly worldwide. In Colombia, it is the most lethal form of cancer. Some single-nucleotide polymorphisms in IL-10, IL-4, and IL-4Rα genes have been associated with an anti-inflammatory environment and a Th2 profile in detriment of the antitumor Th1 response. This research sought to detect single-nucleotide polymorphisms in promoter sequences, like − 1082 (G/A), − 592 (C/A), and − 819 (C/T), as well as − 590 (C/T) of the IL-10 and IL-4 genes, respectively; in addition to the IL-4Rα mutation variants, Ile50Val and Q576R, together with circulating levels of IL-4, TNF-α, IL-10, and IFN-γ in patients with gastric carcinoma in Cúcuta, Colombia.MethodsIn a cross-sectional study, 17 patients and 30 healthy individuals were genotyped for the six polymorphisms mentioned through PCR-RFLP of DNA obtained from peripheral blood cells and serum samples were analyzed by sandwich ELISA to quantify cytokines. Statistical difference between groups was determined along with the association between the presence of polymorphisms and the risk of gastric cancer, as well as the mortality in patients, using Mann-Whitney U test and logistic regression analysis, respectively.ResultsAn association between the − 1082 (G/A) and the risk of gastric cancer was found (OR = 7.58, range 0.77–74.06, P = 0.08). Furthermore, patients had a significant increase in IL-4 serum levels (P < 0.01) compared to healthy individuals, both variables showed a higher estimated risk of mortality in patients, although without statistical association (P > 0.05).ConclusionWe infer that two possible biomarkers (one immunological and one genetic) could be considered in association with gastric cancer in our population, which should be confirmed by subsequent studies involving a greater number of individuals.

Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility

“…Nonetheless, it has been put forward that systemic elevation of Th2 cytokines, observed here particularly in gastric cancer, may indicate a generalized state of immunosuppression and still promote cancer growth and dissemination [ 36 ]. Different association patterns for local and systemic IL-4, concerning sex-dependence [ 15 , 37 ] and relation with the disease advancement [ 13 , 14 ], have been noted also by other authors. Regarding CRC, previous studies have shown circulating IL-4 to be too low to be quantified [ 38 ] or, in contrary, elevated [ 39 , 40 , 41 ] and suitable as a CRC biomarker.…”

“…Furthermore, the interleukin over-secretion has been confirmed already in conditions associated with increased risk of CRC, that is, in ulcerative colitis [46] and adenomatous polyps [41]. Unlike in CRC or esophageal cancer [47,48], an elevation in systemic IL-4 has been unanimously reported in GC [37,47,49], even though its association with pathological findings was inconsistent. On the one hand, IL-4 has been more markedly elevated in patients with higher modified Glasgow Prognostic Score, thus with worse prognosis, but lower in those with more advanced cancers, that is, with vascular invasion or N3 cancers, on the other [49].…”

Possible Roles of Interleukin-4 and -13 and Their Receptors in Gastric and Colon Cancer

“…Gabitass et al found plasma IL-4 levels in 25 GC patients were significantly higher than in 54 healthy controls [ 41 ]. Cárdenas et al found serum IL-4 levels in 17 GC patients were significantly elevated comparing with 30 healthy individuals by sandwich ELISA [ 45 ]. In their study, elevated serum levels of IL-4 indicated a higher risk of mortality, but there is no statistical association [ 45 ].…”

“…Cárdenas et al found serum IL-4 levels in 17 GC patients were significantly elevated comparing with 30 healthy individuals by sandwich ELISA [ 45 ]. In their study, elevated serum levels of IL-4 indicated a higher risk of mortality, but there is no statistical association [ 45 ]. Orea and co-workers studied a total of 30 biopsies of GC by immunohistochemistry [ 46 ].…”

Sintilimab, a PD-1 Inhibitor, Completely Reversed Rarely Refractory Hypofibrinogenemia in a Gastric Cancer Patient: A Case Report and Review of the Literature

“…suppresses its production (10). Patients with gastric carcinoma have increased IL-4 level (11), which may interfere with the production of fibrinogen.…”