ETV/PEA3 Transcription Factor Family Correlated with Immune Infiltrates and Clinical Prognosis in Human Colon Cancer

2019 
Background: Numerous studies have recently pointed to the influence of the immune microenvironment on CRC development, suggesting that infiltration of different types of immune cells might be a promising source of novel diagnostic and prognostic biomarkers. Methods: The correlation of ETV1, ETV4 and ETV5 with tumor-infiltrating immune cells (TIICs) in colon cancer tumor microenvironments via TIMER (Tumor Immune Estimation Resource) and GEPIA (Gene Expression Profiling Interactive Analysis), we validate colon cancer clinical data via immunohistochemistry (IHC). Furthermore, Oncomine database, R2 platform analysis and Oncomine database and R2 platform analysis were applied in our research to validate CRC clinical prognosis via PEA3 members expression level. Findings: Our findings indicated that the upregulation of PEA3 members, ETV1 and ETV5 is correlated with poor prognosis, meanwhile ETV1 and ETV5 may play a role in promoting CRC development. Furthermore, PEA3 members, especially ETV1 and ETV5 tend to have positive correlation with T cell exhaustion markers, and associate with Colon cancer immune infiltration. Interpretation: These findings reveal that ETV1 and ETV5 is a new potential diagnostic and prognostic marker in CRC and that targeting signalling pathways controlled by ETV5 may be a promising strategy for CRC therapy. Funding Statement: Nature Science Foundation of China (NSFC: 81772558), Clinical Skill and Innovation 3 year program of Shanghai Hospital Development Center (16CR2064B), Shanghai Municipal Commission of Health and Family Planing (201540026), Indiana Clinical and Translational Sciences Institute (CTSI) KL2 Young Investigator Award ( KL2TR001106 and UL1TR001108). This is an open access article under the CC BY-NC-ND license. This is an open access article under the CC BY-NC-ND. license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Declaration of Interests: No potential conflicts of interest are disclosed. Ethics Approval Statement: All the experiments involving in human specimens and animals were in accordance with the ethical code and recommendation issued by Ethics Committee of Human Experimentation and Chinese Animal Community and with the Helsinki Declaration of 1975, as revised in 2008.
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