IL35 predicts prognosis in gastric cancer and is associated with angiogenesis by altering TIMP1, PAI1, and IGFBP1.

Tumor angiogenesis is required for tumor growth and metastasis. Interleukin 35 (IL35), a member of the interleukin 12 family, is a dimer comprised of IL12A and EBI3. Elevated plasma IL-35 levels have been reported to be associated with the occurrence and development of tumors. However, the role of IL35 in the angiogenesis of gastric cancer (GC) is still unclear. Here, we report that expression of IL35 is correlated with higher microvessel density (MVD), distant metastasis and poor prognosis in GC. Moreover, in vitro tube formation assays were performed to show that IL35 may contribute to the tube formation abilities of human umbilical vein endothelial cells (HUVECs). IL12A was observed to be the dominant subunit in promotion of tube formation. IL12A also inhibited expression of tissue inhibitor of metalloproteinase 1 (TIMP1) and enhanced expression of plasminogen activator inhibitor 1 (PAI1) and insulin-like growth factor-binding protein 1 (IGFBP1) in a gastric cancer cell line. In conclusion, our data suggest that IL-35 is involved in angiogenesis and is associated with poor prognosis for GC.