Overexpression of IL-32 is a novel prognostic factor in patients with localized clear cell renal cell carcinoma

Abstract

Abstract. ) is a proinflammatory cytokine that acts as a significant pathogenetic factor in various diseases and malignancies. However, the clinical effect of IL-32 expression in renal cell carcinoma (RCC) has not previously been investigated. The aim of the present study was to examine the significance of IL-32 overexpression in localized clear cell RCC (CCRCC). We examined 112 patients with localized CCRCC who underwent nephrectomy. The clinicopathological data were obtained by retrospective review and the expression levels of IL-32 were studied by immunohistochemistry. Tumors were classified according to staining intensity (0, no staining intensity; 1, weak; 2, intermediate; 3, strong). The cases with staining intensities from 0 to 2 comprised the IL-32 low-expression group (LEG), whereas those with a staining intensity of 3 comprised the IL-32 high-expression group (HEG). Correlations between IL-32 expression and clinicopathological parameters were determined. Staining intensities were determined for all cases as follows: 26 cases (23.2%) (score 0), 43 cases (38.4%) (score 1), 31 cases (27.7%) (score 2) and 12 cases (10.7%) (score 3). IL-32 HEG exhibited a higher recurrence rate compared to the IL-32 LEG (50 vs. 13%, P= 0.001). For survival rates, the 5-year recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) rates were lower in the IL-32 HEG group compared with the IL-32 LEG group (RFS, P= 0.001; DSS, P<0.001; OS, P= 0.026, respectively). Univariate analyses revealed that Fuhrman nuclear grade and a high IL-32 expression were significant prognostic factors for predicting RFS, DSS and OS in CCRCC, whereas multivariate analyses indicated that Fuhrman nuclear grade and high IL-32 expression were still independent risk factors. In conclusion, IL-32 overexpression was associated with high recurrence rates and low RFS, DSS and OS, indicating that it may be a novel prognostic factor for predicting outcomes in patients with CCRCC.

IL32 expression in peripheral blood CD3+ cells from myelodysplastic syndromes patients

“…IL-32 has also been proposed as a lung adenocarcinoma prognostic biomarker, in which high IL-32 expression was associated with high grade disease and metastasis incidence [24,25]. In clear cell renal cell carcinoma patients, IL-32 overexpression was associated with disease progression and poor overall survival, indicating that IL-32 may be a novel prognostic factor for predicting outcomes in this disease [26]. Similarly, IL-32 has been reported as a poor prognostic marker for gastric cancer [27,28].…”

Interleukin-32 Gamma as a New Face in Inflammatory Bone Diseases

“…There are 9 different splice variants in humans: IL-32α, IL-32β, [34][35][36][37][38] Chronic inflammation and autoimmune disease Elevated IL-32 level in chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis (CRS), inflammatory bowel disease [9,13,39,40] Inflammatory bone disease Rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoporosis [3][4][5] IL-32γ, IL-32δ, IL-32ε, IL-32ξ, IL-32η, IL-32θ, and IL-32ζ [6], and different isoforms of IL-32 have diverse biological functions. IL-32 is now recognized as a proinflammatory cytokine produced in epithelial cells, NK cells, CD4 + T cells, and synovial fibroblasts in response to various cytokines such as IL-1β, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-6, IL-8, IL-12, and IL-18 [12][13][14].…”

“…IL-32 expression is also noted in hepatocellular carcinoma and pancreatic cancer [36,37]. Lee et al [38] demonstrated the significance of IL-32 as a novel prognostic factor in patients with localized clear cell renal cell carcinoma (CCRCC). The patients with elevated IL-32 expression are more likely to have high recurrence rates and low survival rates compared to individuals with low IL-32 expression.…”

Interleukin-32 stimulates osteosarcoma cell invasionand motility via AKT pathway-mediated MMP-13 expression

“…Although the receptor for IL-32 remains to be determined, IL-32 has been found to stimulate TNF-α, IL-1β and IL-8 production and thus act as a pro-inflammatory mediator in inflammatory diseases and tumor (7,10). IL-32 expression is increased in malignant esophageal tissues (11), and overexpression of IL-32 is reversely associated with 5-year recurrence-free, disease-specific and overall survival rates in localized clear cell renal cell carcinoma (12). However, the role of IL-32 in osteosarcoma progression remains to be elucidated.…”