Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1808
Peer-review started: February 28, 2022
First decision: April 17, 2022
Revised: April 21, 2022
Accepted: July 31, 2022
Article in press: July 31, 2022
Published online: September 15, 2022
Processing time: 192 Days and 13.4 Hours
Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality. Despite the more widespread use of recent diagnostic techniques, including endoscopic examination, many GC patients are diagnosed at advanced stages, resulting in a poor 5-year survival rate, emphasizing the critical need for development of a reliable biomarker(s) with high specificity and sensitivity to improve the prediction of prognosis for more successful outcomes for GC patients. Endoscopic examination provides a useful approach in the early detection of GC, and in reducing cancer-related mortality.
The cell-mediated immune response is extremely important in defence against tumour development, since compromised host immunity is known to contribute to the establishment, proliferation, and metastasis of malignant tumours. Although high host inflammatory status has been reported in the tumour microenvironment, an incompetent inflammatory/immune response will lead to tumour progression.
We aimed to identify the expression of interleukin (IL)-31, IL-32, and IL-33 in GC and assess their inter-correlation and clinical significance.
GC tissues were obtained from patients without local recurrences for immunohistochemistry to determine the expression of IL-31, IL-32, and IL-33. Additionally, circulating levels of IL-31, 32, 33 were determined using ELISA. The Mann-Whitney U test or the Kruskal-Wallis test was used for statistical analysis.
IL-31, IL-32, and IL-33 expression was all lower in GC than in adjacent non-cancer gastric tissues (P < 0.05). IL-33 level in peripheral blood of GC patients was significantly lower than that of healthy individuals (1.50 ± 1.11 vs 9.61 ± 8.00 ng/mL, (P < 0.05). Decreased IL-31, IL-32, and IL-33 expression in GC was observed in younger patients (< 60 years), and IL-32 and IL-33 expression was lower in female patients (P < 0.05). Higher IL-32 expression correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM stage I-II. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people (P < 0.05).
IL-31, IL-32, and IL-33 expression in GC is all decreased, which correlates with younger age of the GC patients. IL-32 and IL-33 expression also correlates with the sex of the GC patients. Decreased IL-32 correlates with a poorer survival of GC patients in the T4 stage and TNM stage I-II subgroups. Down-regulation of IL-32 is an independent prognostic factor for survival of T4 GC patients. Finally, low IL-33 in peripheral blood may be considered as an objective predictive marker for the development of GC.
Further studies are required to investigate the mechanism of action of these ILs in GC.