Abstract
Background: Colony-stimulating factor-1 (CSF1) is a cytokine that is closely related to normal organ growth and development as well as tumor progression.
Objective: We aimed to summarize and clarify the reasons for the abnormal expression of CSF1 in tumors and explore the role of CSF1 in tumor progression. Furthermore, drug response analysis could provide a reference for clinical medication.
Methods: The expression of CSF1 was analyzed by TCGA and CCLE. Besides, cBioPortal and MethSurv databases were used to conduct mutation and DNA methylation analyses. Further, correlations between CSF1 expression and tumor stage, survival, immune infiltration, drug sensitivity and enrichment analyses were validated via UALCAN, Kaplan-Meier plotter, TIMER, CTRP and Coexperia databases.
Results: CSF1 is expressed in a variety of tissues; meaningfully, it can be detected in the blood. Compared with normal tissues, CSF1 expression was significantly decreased in most tumors. The missense mutation and DNA methylation of CSF1 might cause the downregulated expression. Moreover, decreased CSF1 expression was related to higher tumor stage and worse survival. Further, the promoter DNA methylation level of CSF1 was prognostically significant in most tumors. Besides, CSF1 was closely related to immune infiltration, especially macrophages. Importantly, CSF1 expression was associated with a good response to VEGFRs inhibitors, which may be due to the possible involvement of CSF1 in tumor angiogenesis and metastasis processes.
Conclusion: The abnormal expression of CSF1 could serve as a promising biomarker of tumor progression and prognosis in pan-cancer. Significantly, angiogenesis and metastasis inhibitors may show a good response to CSF1-related tumors.
Keywords: CSF1, pan-cancer, mutation, DNA methylation, immune infiltration, drug sensitivity.
Graphical Abstract
[http://dx.doi.org/10.1038/274168a0] [PMID: 307187]
[http://dx.doi.org/10.1002/JLB.MA0519-149R] [PMID: 31397014]
[http://dx.doi.org/10.3389/fimmu.2019.02199] [PMID: 31616414]
[http://dx.doi.org/10.1371/journal.pone.0137515] [PMID: 26407006]
[http://dx.doi.org/10.1155/2016/4549676] [PMID: 26884646]
[http://dx.doi.org/10.1371/journal.pone.0056951] [PMID: 23451116]
[http://dx.doi.org/10.1677/joe.1.06225] [PMID: 16522727]
[http://dx.doi.org/10.4236/abb.2019.1010027] [PMID: 31750010]
[http://dx.doi.org/10.1186/2045-824X-5-4] [PMID: 23422217]
[http://dx.doi.org/10.1007/s10456-016-9523-8] [PMID: 27464987]
[http://dx.doi.org/10.1002/eji.201948164] [PMID: 31251389]
[http://dx.doi.org/10.1038/s41586-019-1105-7] [PMID: 30971820]
[http://dx.doi.org/10.21873/anticanres.13854] [PMID: 31704874]
[http://dx.doi.org/10.3389/fimmu.2019.01273] [PMID: 31214202]
[http://dx.doi.org/10.1002/gcc.22807] [PMID: 31469468]
[http://dx.doi.org/10.1002/jcb.25792] [PMID: 27862217]
[http://dx.doi.org/10.3892/mmr.2019.9963] [PMID: 30816518]
[http://dx.doi.org/10.18632/oncotarget.19953] [PMID: 29137220]
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1934] [PMID: 31911555]
[http://dx.doi.org/10.1016/j.biopha.2019.109523] [PMID: 31655310]
[http://dx.doi.org/10.1089/ars.2017.7201] [PMID: 29634345]
[http://dx.doi.org/10.1002/ijc.32763] [PMID: 31671219]
[http://dx.doi.org/10.1155/2019/2724948] [PMID: 31565097]
[http://dx.doi.org/10.1080/17512433.2020.1771179] [PMID: 32478598]
[http://dx.doi.org/10.1016/S0140-6736(19)30764-0] [PMID: 31229240]
[http://dx.doi.org/10.1186/s13046-019-1357-y] [PMID: 31438996]
[http://dx.doi.org/10.1038/s41467-020-15290-0] [PMID: 32286255]
[http://dx.doi.org/10.1126/science.1260419] [PMID: 25613900]
[http://dx.doi.org/10.1186/s13059-016-1028-7] [PMID: 27549193]
[http://dx.doi.org/10.1126/scisignal.2004088] [PMID: 23550210]
[http://dx.doi.org/10.2217/epi-2017-0118] [PMID: 29264942]
[http://dx.doi.org/10.1016/j.neo.2017.05.002] [PMID: 28732212]
[http://dx.doi.org/10.1038/s41598-018-27521-y] [PMID: 29907753]
[http://dx.doi.org/10.1158/2159-8290.CD-15-0235] [PMID: 26482930]
[http://dx.doi.org/10.1038/nchembio.1986] [PMID: 26656090]
[http://dx.doi.org/10.1093/nar/gkw868] [PMID: 27679477]
[http://dx.doi.org/10.3892/ol.2019.10642] [PMID: 31452779]
[http://dx.doi.org/10.1530/ERC-13-0198] [PMID: 24016870]
[http://dx.doi.org/10.1007/s00404-015-3931-7] [PMID: 26538356]
[http://dx.doi.org/10.3343/alm.2016.36.3.223] [PMID: 26915610]
[http://dx.doi.org/10.1007/s00784-019-02935-8] [PMID: 31102043]
[http://dx.doi.org/10.1073/pnas.0507321103] [PMID: 16407111]
[http://dx.doi.org/10.3390/cancers12010100] [PMID: 31906059]
[http://dx.doi.org/10.1007/s11427-016-0253-7] [PMID: 28063009]
[http://dx.doi.org/10.1186/2045-3701-4-46] [PMID: 25949795]
[http://dx.doi.org/10.1186/s40425-017-0257-y] [PMID: 28716061]
[http://dx.doi.org/10.1038/s41375-021-01201-9] [PMID: 33731849]
[http://dx.doi.org/10.2174/0929867327666200203113926] [PMID: 32013816]
[http://dx.doi.org/10.1002/hon.2705] [PMID: 31872891]
[http://dx.doi.org/10.1007/s10456-018-9648-z] [PMID: 30238211]
[http://dx.doi.org/10.3892/ijo.2018.4406] [PMID: 29767252]
[http://dx.doi.org/10.1016/j.lungcan.2015.09.011] [PMID: 26424209]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3126] [PMID: 21363918]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-1486] [PMID: 31636099]
[http://dx.doi.org/10.1002/mc.22602] [PMID: 27996164]
[http://dx.doi.org/10.1016/j.bcp.2018.07.011] [PMID: 30012461]
[http://dx.doi.org/10.1002/ijc.32421] [PMID: 31107544]
[http://dx.doi.org/10.1186/s13045-020-00997-w] [PMID: 33402221]
[http://dx.doi.org/10.1186/s12864-019-5976-7] [PMID: 31366318]
[http://dx.doi.org/10.1038/bjc.2014.337] [PMID: 24937670]
[http://dx.doi.org/10.18383/j.tom.2018.00031] [PMID: 30854442]
[http://dx.doi.org/10.1080/21691401.2019.1671855] [PMID: 31571495]
[http://dx.doi.org/10.1016/j.lungcan.2016.11.019] [PMID: 28024697]
[http://dx.doi.org/10.1016/j.juro.2014.11.091] [PMID: 25433307]
[http://dx.doi.org/10.2147/DDDT.S253232] [PMID: 32440095]
[http://dx.doi.org/10.1177/1947601911423031] [PMID: 22866201]
[PMID: 32642296]
[http://dx.doi.org/10.1136/jitc-2019-000182] [PMID: 32581053]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01298] [PMID: 23670300]
[http://dx.doi.org/10.1016/j.ajpath.2011.06.021] [PMID: 21854753]
[http://dx.doi.org/10.18632/oncotarget.8718] [PMID: 27107415]
[http://dx.doi.org/10.1080/2162402X.2015.1122157] [PMID: 27141406]