Local and Systemic Interleukin-32 in Esophageal, Gastric, and Colorectal Cancers: Clinical and Diagnostic Significance

Abstract

Little is known on clinical and diagnostic relevance of interleukin-32 in gastrointestinal tract (GIT) cancers. We determined its mRNA (n = 52) and protein (n = 63) expression in paired (tumor-normal) samples from esophageal squamous cell carcinoma (ESCC) and gastric (GC) and colorectal cancer (CRC) patients, with reference to cancer-associated genes, and quantified circulating interleukin-32 in 70 cancer patients and 28 controls. IL32 expression was significantly upregulated solely in ESCC, reflecting T stage in non-transformed tumor-adjacent tissue. Fold-change in IL32 and IL-32 was higher in left-sided CRC, owing to high interleukin expression in non-transformed right-sided colonic mucosa. IL32 was independently and positively associated with Ki67, HIF1A, and ACTA2 and negatively with TJP1 in tumors and with IL10Ra and BCLxL in non-transformed tumor-adjacent tissue. IL-32 protein was significantly upregulated in colorectal tumors. In ESCC, advanced stage and lymph node metastasis were associated with significant IL-32 upregulation. Circulating interleukin was significantly elevated in cancer patients, more so in ESCC and GC than CRC. As biomarker, IL-32 detected gastroesophageal cancers with 99.5% accuracy. In conclusion, IL-32 is upregulated in GIT cancers at local and systemic level, reflecting hypoxia and proliferative and invasive/metastatic capacity in tumors and immunosuppressive and antiapoptotic potential in non-transformed mucosa, while being an accurate biomarker of gastroesophageal cancers.

Keywords

• inflammation
• epithelial-mesenchymal transition
• cancer biomarker
• anatomical subsite heterogeneity
• immunomodulator
• metastasis