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Interleukin-35 expression is associated with colon cancer progression
Jian Zhang1, Tao Mao1, Shuyun Wang1
1Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
Oncotarget
|October 27, 2017
Summary
Interleukin 35 (IL-35), an anti-inflammatory factor, is downregulated in colon cancer. Lower IL-35 levels correlate with advanced disease and poor survival, suggesting IL-35 is a potential therapeutic target for colon cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Colon cancer development is linked to inflammation.
- Interleukin 35 (IL-35) is a newly identified anti-inflammatory cytokine.
- The role of IL-35 in colon cancer pathogenesis is not well understood.
Purpose of the Study:
- To investigate the expression of IL-35 in colon cancer tissues.
- To determine the correlation between IL-35 expression and clinicopathological features and patient survival.
- To evaluate the functional role of IL-35 in colon cancer progression and chemosensitivity.
Main Methods:
- Quantitative PCR (qPCR), ELISA, and tissue microarrays were used to assess IL-35 expression in 186 paired colon cancer and adjacent normal tissues.
- Statistical analyses were performed to correlate IL-35 levels with AJCC stage, nodal involvement, invasion depth, metastasis, differentiation, and survival outcomes.
- In vitro (cell lines) and in vivo (mice models) experiments were conducted to assess the effects of IL-35 overexpression on cancer cell behavior and tumor formation, including its impact on the Wnt/β-catenin pathway and chemosensitivity.
Main Results:
- IL-35 expression was significantly downregulated in colon cancer tissues compared to adjacent normal tissues.
- Reduced IL-35 expression was strongly associated with advanced AJCC stage, lymph node metastasis, deeper invasion, distant metastasis, poor differentiation, and shorter disease-free and overall survival.
- Overexpression of IL-35 suppressed colon cancer cell migration, invasion, proliferation, and cancer stem cell characteristics by inhibiting the Wnt/β-catenin pathway. IL-35 also inhibited tumor formation in mice and enhanced sensitivity to chemotherapy drugs.
Conclusions:
- IL-35 exhibits an inhibitory role in colon cancer development.
- Downregulation of IL-35 is a significant prognostic biomarker for colon cancer patients.
- IL-35 represents a potential therapeutic target for colon cancer treatment.
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