Background: To determine whether IL-31, IL-32 and IL-33 can be used as biomarkers for the detection of gastric cancer (GC), via evaluating the correlations between IL-31, IL-32 and IL‑33 expression and clinicopathological parameters of GC patients.
Methods: Tissue array (n=180) gastric specimens were utilised. IL-31, IL-32 and IL-33 in GC and non-GC tissues were detected immunohistochemically. The correlations between IL-31, IL-32 and IL-33 in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier/Cox regression. IL-31, IL-32 and IL-33 in circulation were detected by ELISA.
Results: IL-31, IL-32 and IL-33 were all lower in GC than that in adjacent non-GC gastric tissue (p all <0.05). IL-33 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 in GC were observed in younger patients (<60 years), and IL-32 and IL-33 were lower in female patients (p all <0.05). Higher IL-32 correlated with longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 is an independent prognostic factor for GC within the T4 stage subgroup. Circulation IL-33 was significantly lower in GC patients than healthy people (p <0.05).
Conclusions: Our findings provide new insights into the roles of IL-31, IL-32 and IL-33 in carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32 and IL-33 in GC is further discussed.

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This is a list of supplementary files associated with this preprint. Click to download.
Supplementary Figure 1 Correlation of IL-31, IL-32 and IL-33 expression with clinicopathological parameters of tumour size, lymph node metastasis, tumour differentiation and tumour invasion depth subtypes of GC IL-31, IL-32 and IL-33 all have no correlations with any clinicopathological parameters of tumour size, lymph node metastasis, tumour differentiation and tumour invasion depth subtypes of GC. Supplementary Figure 2 Correlation of IL-31, IL-32 and IL-33 expression with clinicopathological parameter of TNM subtype of GC and IL-31 expression with gender subtype of GC IL-31, IL-32 and IL-33 all have no correlations with clinicopathological parameter of TNM subtype of GC. Moreover, no significant differences were observed in IL-31 with gender of GC. Supplementary Figure 3 Survival analysis of IL-31, IL-32 and IL-33 for prognosis of subtypes of GC patients Kaplan-Meier survival analysis of IL-31, IL-32 and IL-33 for prognosis of GC in tumour invasion depth T3, TNM III- IV stage and yes/no lymph node metastasis subtypes of GC patients. Supplementary Figure 4 Survival analysis of IL-31, IL-32 and IL-33 for prognosis of subtypes of GC patients Kaplan-Meier survival analysis of IL-31, IL-32 and IL-33 for prognosis of GC subtypes of tumour differentiation and size. Supplementary Figure 5 Survival analysis of IL-31, IL-32 and IL-33 for prognosis of subtypes of GC patients Kaplan-Meier survival analysis of IL-31, IL-32 and IL-33 for prognosis of GC subtypes of age and gender of tumour patients. Supplementary Figure 6 Survival analysis of combination of IL-31, IL-32 and IL-33 for prognosis of GC Kaplan-Meier survival analysis of combinations of IL-31, IL-32 and IL-33 for prognosis of GC
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Posted 21 Dec, 2020
Posted 21 Dec, 2020
Background: To determine whether IL-31, IL-32 and IL-33 can be used as biomarkers for the detection of gastric cancer (GC), via evaluating the correlations between IL-31, IL-32 and IL‑33 expression and clinicopathological parameters of GC patients.
Methods: Tissue array (n=180) gastric specimens were utilised. IL-31, IL-32 and IL-33 in GC and non-GC tissues were detected immunohistochemically. The correlations between IL-31, IL-32 and IL-33 in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier/Cox regression. IL-31, IL-32 and IL-33 in circulation were detected by ELISA.
Results: IL-31, IL-32 and IL-33 were all lower in GC than that in adjacent non-GC gastric tissue (p all <0.05). IL-33 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 in GC were observed in younger patients (<60 years), and IL-32 and IL-33 were lower in female patients (p all <0.05). Higher IL-32 correlated with longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 is an independent prognostic factor for GC within the T4 stage subgroup. Circulation IL-33 was significantly lower in GC patients than healthy people (p <0.05).
Conclusions: Our findings provide new insights into the roles of IL-31, IL-32 and IL-33 in carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32 and IL-33 in GC is further discussed.

Figure 1

Figure 2

Figure 3

Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Supplementary Figure 1 Correlation of IL-31, IL-32 and IL-33 expression with clinicopathological parameters of tumour size, lymph node metastasis, tumour differentiation and tumour invasion depth subtypes of GC IL-31, IL-32 and IL-33 all have no correlations with any clinicopathological parameters of tumour size, lymph node metastasis, tumour differentiation and tumour invasion depth subtypes of GC. Supplementary Figure 2 Correlation of IL-31, IL-32 and IL-33 expression with clinicopathological parameter of TNM subtype of GC and IL-31 expression with gender subtype of GC IL-31, IL-32 and IL-33 all have no correlations with clinicopathological parameter of TNM subtype of GC. Moreover, no significant differences were observed in IL-31 with gender of GC. Supplementary Figure 3 Survival analysis of IL-31, IL-32 and IL-33 for prognosis of subtypes of GC patients Kaplan-Meier survival analysis of IL-31, IL-32 and IL-33 for prognosis of GC in tumour invasion depth T3, TNM III- IV stage and yes/no lymph node metastasis subtypes of GC patients. Supplementary Figure 4 Survival analysis of IL-31, IL-32 and IL-33 for prognosis of subtypes of GC patients Kaplan-Meier survival analysis of IL-31, IL-32 and IL-33 for prognosis of GC subtypes of tumour differentiation and size. Supplementary Figure 5 Survival analysis of IL-31, IL-32 and IL-33 for prognosis of subtypes of GC patients Kaplan-Meier survival analysis of IL-31, IL-32 and IL-33 for prognosis of GC subtypes of age and gender of tumour patients. Supplementary Figure 6 Survival analysis of combination of IL-31, IL-32 and IL-33 for prognosis of GC Kaplan-Meier survival analysis of combinations of IL-31, IL-32 and IL-33 for prognosis of GC
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