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.
Highlights
Lung cancer is the leading cause of cancer death and one of the most common cancers among both men and women worldwide[1]
We describe for the first time the clinicopathological relevance of macrophage colony-stimulating factor (M-CSF) and interleukin 34 (IL-34) expression with disease stages and poor survival in a cohort of lung cancer patients
Our data showed that single expression of M-CSF or IL-34 can be observed in primary lung cancer tissues and correlated with poor survival
Summary
Lung cancer is the leading cause of cancer death and one of the most common cancers among both men and women worldwide[1]. M-CSF and IL-34 share no sequence homology, but show comparable biological activities in myeloid cells[16,17] Both cytokines correlate with tumor progression, metastasis, angiogenesis and therapeutic resistance[9]. It has been suggested that expression of IL-34 or M-CSF is accompanied with increased infiltration of M2-polarized TAMs that show enhanced pro-tumorigenic functions[18,19] Based on these backgrounds, the expression of IL-34 and/or M-CSF at the TME may characterize tumors with enhanced aggression and has an impact on the patient’s survival. The expression of IL-34 and/or M-CSF at the TME may characterize tumors with enhanced aggression and has an impact on the patient’s survival In this regard, previous reports have related M-CSF expression with poor survival in cancer patients[20,21]. We analyze the expression of IL-34 and M-CSF in primary lung cancer tissues and its correlation with survival and tumor progression in a cohort of lung cancer patients, providing for the first time an evidence that show the association between IL-34 and M-CSF expression with disease progression and poor survival in lung cancer patients
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