FUT4 is involved in PD-1-related immunosuppression and leads to worse survival in patients with operable lung adenocarcinoma
As an important glycosyltransferase, fucosyltransferase IV (FUT4) is abnormally upregulated in different types of cancers, but its clinical role remains inexplicit. This work aimed to determine the predictive ability of FUT4 in lung adenocarcinoma (LUAD) after curative resection, as well as to explore the role of a possible FUT4 molecular mechanism on LUAD malignant behavior.
A total of 273 LUAD patients after curative resection with complete clinicopathological and RNAseq data from The Cancer Genome Atlas (TCGA) cohort were collected. Correlation of FUT4 with overall survival (OS) was analyzed based on TCGA and further validated by online “Kaplan–Meier Plotter” database and IHC in 70 LUAD patients recruited in the First Hospital of China Medical University cohort. Multivariate Cox regression analysis and 1000 bootstrapping were performed to verify the predictive value of FUT4. Gene set enrichment assay (GSEA) was performed to investigate the biological characteristics. Correlation between PD-1 and FUT4 was analyzed based on TCGA cohort and validated by IHC on cohort from our hospital.
Increased FUT4 expression led to reduced overall survival (OS) of LUAD patients based on TCGA (p = 0.006 and 0.001 for dichotomous and trichotomous modeling, respectively) and externally validated in KMPLOTTER (p = 0.01) and by IHC based on cohort from our hospital (p = 0.005 and p = 0.019 for dichotomous and trichotomous modeling, respectively). FUT4 overexpression was an independent high risk factor for OS along with advanced pT stage and pTNM stage (p = 0.001, p = 0.037, and p < 0.001, respectively). GSEA revealed that FUT4 overexpression might correlate with shortened survival of LUAD patients by promoting cell proliferation via ERBB signaling, and suppressing immune response-related pathways. FUT4 expression positively correlated with PD-1 in TCGA (p = 0.026) and validated by IHC on cohort from our hospital (p = 0.029).
Increased FUT4 expression led to reduced OS in operable LUAD. FUT4 showed significant correlation with immune response and PD-1 expression.
KeywordsFUT4 Lung adenocarcinoma PD-1 Prognosis Survival
We thank Huihui Xu for her technical support. This work was supported by National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2017ZX09304025), the National Key Research and Development Program of China (No. 2017YFC1308900), Distinguished Professor of Liaoning Province, Science and Technology Plan Project of Liaoning Province (Nos. 2016007010, 2015020457), Foundation for selected Overseas Chinese Scholar 2015, the general project of Liaoning Province department of education (No. LZ2015073), and the Key Research and Development Program of Shenyang (No. 17-230-9-01).
This work was supported by National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2017ZX09304025), the National Key Research and Development Program of China (No. 2017YFC1308900), Distinguished Professor of Liaoning Province, Science and Technology Plan Project of Liaoning Province (No. 2016007010, 2015020457), Foundation for selected Overseas Chinese Scholar 2015, the general project of Liaoning Province department of education (No. LZ2015073), and the Key Research and Development Program of Shenyang (No. 17-230-9-01).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Ethics Committee of the First Hospital of China Medical University approved the project and the study number of IRB approval is 2014-2014-25-2.
Informed consent was obtained from all individual participants included in the study.
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