High co-expression of IL-34 and M-CSF correlates with tumor progression and poor survival in lung cancers

Abstract

Despite recent advances in diagnosis and treatment of lung cancers, the 5-year survival rate remains unsatisfactory, which necessitates the identification of novel factors that associates with disease progression and malignant degree for improving diagnostic and therapeutic strategies. Recent progress in cancer immunology research has unveiled critical roles for colony stimulating factor 1 receptor (CSF1R) in multiple aspects of the tumor microenvironment. CSF1R is expressed on tumor-associated macrophages (TAMs), and mediates important pro-tumorigenic functions. CSF1R also provides critical autocrine signals that promote cancer cell survival and proliferation. Activation of CSF1R can be achieved by two independent ligands; macrophage colony-stimulating factor (M-CSF) and interleukin 34 (IL-34). Accordingly, the expression of these ligands in cancer is expected to result in poor prognosis. In this study, we show that IL-34 and M-CSF expression correlates with poor survival in a cohort of lung cancer patients. Importantly, high co-expression of IL-34 and M-CSF associates with the poorest survival compared to cancers that show weak or absent expression of the two ligands. Furthermore, high expression of IL-34 and M-CSF associates with advanced stages of lung cancers. Together, these results indicate a correlation between IL-34/M-CSF expression with poor survival and disease progression in lung cancer patients.

High serum interleukin‐34 level is a predictor of poor prognosis in patients with non‐viral hepatocellular carcinoma

“…16 Moreover, IL-34 expression is known to be associated with therapeutic resistance in lung cancer and melanoma. 33,36,37 Therefore, in this study, serum IL-34 level could reflect hepatic fibrosis as well as tumor factors, and was associated with the prognosis of patients with nonviral HCC.…”

“…Baghdadi et al . reported that high expression of IL‐34 was associated with poor survival in patients with lung cancer, and Zhou et al . reported that high IL‐34 levels indicated a poor prognosis with shorter overall survival in patients with HCC after curative resection .…”

“…In the present study, serum IL-34 level was an independent risk factor for prognosis of patients with non-viral HCC. Baghdadi et al reported that high expression of IL-34 was associated with poor survival in patients with lung cancer, 33 and Zhou et al reported that high IL-34 levels indicated a poor prognosis with shorter overall survival in patients with HCC after curative resection. 18 Therefore, our results are in good agreement with those of previous reports.…”

A multi-layered systems approach for renal cell carcinoma

“…IL34 supports the growth and survival of primary human monocytes and induces their differentiation into type 2 macrophages 53 IL34 has been linked with autoimmune and inflammatory diseases such as rheumatoid arthritis 53,54 , hepatitis C infection 55 , lupus nephritis 56 , inflammatory bowel disease 57 . It has been linked to chronic kidney injury and kidney graft rejection 52 , and to cancers including osteosarcoma 58 or lung cancer 59 .…”

“…We further confirmed the increase in type 2 macrophage density in the tail vein metastasis assay. It is known that Type 2 macrophages are associated with worsened progression in multiple cancer types 59 .…”