Circulating inflammation‐related markers and advanced gastric premalignant lesions

Abstract

Background and Aim Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori‐infected individuals. Methods We compared pre‐treatment serum levels of immune‐related and inflammation‐related markers between 99 individuals with intestinal metaplasia or dysplasia and 75 control individuals with non‐atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead‐based assays were categorized in tertiles as low (T1), middle (T2), and high (T3). Logistic regression models were used to calculate age‐adjusted and sex‐adjusted odds ratios and 95% confidence intervals. All statistical tests were two‐sided, and significance values were adjusted for multiple comparisons using false discovery rate methods. Results Five markers were nominally associated (Ptrend < 0.05) with the presence of advanced premalignant gastric lesions. Adjusted odds ratios (95% confidence interval) of T2 and T3 versus T1 were 4.09 (1.65–10.17) and 3.08 (1.23–7.68) for CCL3/MIP1A, 3.21 (1.33–7.75) and 2.69 (1.10–6.57) for CCL20/MIP3A levels, 1.79 (0.77–4.18) and 2.39 (1.02–5.60) for IL‐1β, 1.34 (0.56–3.19) and 3.02 (1.29–7.12) for IL‐4, and 1.07 (0.44–2.59) and 3.07 (1.32–7.14) for IL‐5, respectively. Two (IL‐4 and IL‐5) of the five markers had false discovery rate adjusted Ptrend < 0.2. Conclusions Our results suggest that certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre‐diagnostic samples, and elucidate the underlying mechanisms.

Systemic interleukin 10 levels indicate advanced stages while interleukin 17A levels correlate with reduced survival in esophageal adenocarcinomas

“…This assumption is supported by a study in which increased systemic levels of IL-10 and decreased levels of IL-4 have been found investigating EAC and ESCC together [21]. Conversely, in gastric cancers increased levels of both serum IL-10 and IL-4 have been reported [22][23][24][25][26]. These findings emphasize the use of both systemic IL-10 and IL-4 as potential biomarkers in EACs.…”

“…On the other hand, anti-inflammatory cytokines like IL-4 and IL-10 have a predominantly regulatory function in the immune system [19,20]. Increased as well as decreased levels of IL-4 and IL-10 have been reported in esophageal and gastric cancers and their prognostic value remains uncertain [21][22][23][24][25][26]. However, one meta-analysis identified serum IL-10 as a negative prognostic marker in several gastrointestinal malignancies including colon and gastric cancers.…”

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.…”

“…However, available literature data concerning IL-4 and IL-13 in CRC and upper GIT cancers are fragmentary and frequently inconsistent. Contradicting findings have been reported, especially concerning the interleukins’ status at local and systemic level and their association with the disease advancement [ 13 , 14 , 15 ]. Consequently, both tumor promoting [ 10 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ] and protective roles [ 14 , 15 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] have been advocated for IL-4 and IL-13.…”

The Variation of Peripheral Inflammatory Markers in Vocal Leukoplakia before and after Recurrence and Canceration

“…It is commonly known that chronic inflammatory status, caused by Helicobacter pylori infection [ 7 ] or laryngopharyngeal reflux [ 8 ] and other incentives, is a long-term factor in laryngeal lesions. Previous researches described the potential interrelation between systematic markers and local inflammation [ 9 ], and peripheral blood markers had been applied to evaluate the clinical responses of many diseases, including advanced colorectal neoplasia [ 10 ], gastric premalignant lesions [ 11 ], gynecological cancers [ 12 ], and the precancerous laryngeal lesions [ 13 , 14 ]. Our previous research focused on the horizontal comparison of VFL with benign and malignant lesions of vocal cord and managed to find significant markers [ 15 ]; however, few investigations were made in the longitudinal and self-control comparison methods.…”