Identification of <i>FUT7</i> hypomethylation as the blood biomarker in the prediction of early-stage lung cancer

Rong Qiao; Feifei Di; Jun Wang; Yujie Wei; Tian Xu; Liping Dai; Wanjian Gu; Baohui Han; Rongxi Yang

doi:10.1016/j.jgg.2023.02.014

Volume 50 Issue 8

Aug. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(8): 573-581

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Identification of FUT7 hypomethylation as the blood biomarker in the prediction of early-stage lung cancer

doi: 10.1016/j.jgg.2023.02.014

a Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China;
b Nanjing TANTICA Biotechnology Co. Ltd, Nanjing, Jiangsu 210061, China;
c Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, China;
d Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan 450001, China;
e Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
f Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
g Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China

Funds:

This work was supported by the Nanjing Social Supporting Department and Social Supporting Ministry of Jiangsu Province granted from 2018 to 2020, and the Nanjing TANTICA Co. Ltd (grant no. 2018LC01.1).

Received Date: 2022-07-20
Revised Date: 2023-02-09
Accepted Date: 2023-02-17
Publish Date: 2023-03-08

Abstract

Abstract

Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. Here, LC-associated hypomethylation in alpha-1,3-fucosyltransferase VII (FUT7) is identified via the Illumina 850K array in a discovery study and validated by mass spectrometry in two independent casecontrol studies with blood samples from 1720 LC patients (86.8% LC at stage I, blood is collected before surgery and treatment) and 3143 healthy controls. Compared to the controls, blood-based FUT7 hypomethylation is identified in LC patients at stage I, and even in LC patients with malignant nodules ≤1 cm and in patients with adenocarcinoma in situ. Gender plays a role in the LC-associated FUT7 hypomethylation in blood, which is more significant in males than in females. We also reveal that FUT7 hypomethylation in LC could be enhanced by the advanced stage of cancer, involvement of lymph nodes, and larger tumor size. Based on a large sample size and semi-quantitative methods, our study reveals a strong association between blood-based FUT7 hypomethylation and LC, suggesting that methylation signatures in blood may be a group of potential biomarkers for detection of early-stage LC.
- Lung cancer,
- Early detection,
- DNA methylation,
- FUT7,
- Mass spectrometry

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References(55)

References

Aberle, D.R., Adams, A.M., Berg, C.D., Black, W.C., Clapp, J.D., Fagerstrom, R.M., Gareen, I.F., Gatsonis, C., Marcus, P.M., Sicks, J.D., 2011. Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med. 365, 395-409.

Aravanis, A.M., Lee, M., Klausner, R.D., 2017. Next-generation sequencing of circulating tumor DNA for early cancer detection. Cell 168, 571-574.

Baylin, S.B., Jones, P.A., 2011. A decade of exploring the cancer epigenome d biological and translational implications. Nat. Rev. Cancer 11, 726-734.

Beegle, S.H., Barba, K., Gobunsuy, R., Judson, M.A., 2013. Current and emerging pharmacological treatments for sarcoidosis:a review. Drug Des. Dev. Ther. 7, 325-338.

Bi, H., Liu, Y., Pu, R., Xia, T., Sun, H., Huang, H., Zhang, L., Zhang, Y., Liu, Y., Xu, J., et al., 2019. CHST7 gene methylation and sex-specific effects on colorectal cancer risk. Dig. Dis. Sci. 64, 2158-2166.

Castro-Giner, F., Gkountela, S., Donato, C., Alborelli, I., Quagliata, L., Ng, C.K.Y., Piscuoglio, S., Aceto, N., 2018. Cancer diagnosis using a liquid biopsy:challenges and expectations. Diagnostics 8, 31.

Chansky, K., Detterbeck, F.C., Nicholson, A.G., Rusch, V.W., Vallieres, E., Groome, P., Kennedy, C., Krasnik, M., Peake, M., Shemanski, L., et al., 2017. The IASLC lung cancer staging project:external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer. J. Thorac. Oncol. 12, 1109-1121.

Chen, X., Gole, J., Gore, A., He, Q., Lu, M., Min, J., Yuan, Z., Yang, X., Jiang, Y., Zhang, T., et al., 2020. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nat. Commun. 11, 3475.

Costabel, U., Hunninghake, G.W., 1999. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World association for sarcoidosis and other granulomatous disorders. Eur. Respir. J. 14, 735-737.

Coveney, S., McCabe, J.J., Murphy, S., O'Donnell, M., Kelly, P.J., 2020. Anti-inflammatory therapy for preventing stroke and other vascular events after ischaemic stroke or transient ischaemic attack. Cochrane Database Syst. Rev. 5, CD012825.

de Koning, H.J., Meza, R., Plevritis, S.K., ten Haaf, K., Munshi, V.N., Jeon, J., Erdogan, S.A., Kong, C.Y., Han, S.S., van Rosmalen, J., et al., 2014. Benefits and harms of computed tomography lung cancer screening strategies:a comparative modeling study for the U.S. Preventive Services Task Force. Ann. Intern. Med. 160, 311-320.

Farhan, H., Schuster, C., Klinger, M., Weisz, E., Waxenecker, G., Schuster, M., Sexl, V., Mudde, G.C., Freissmuth, M., Kircheis, R., 2006. Inhibition of xenograft tumor growth and down-regulation of ErbB receptors by an antibody directed against Lewis Y antigen. J. Pharmacol. Exp. Ther. 319, 1459-1466.

Gao, C., Maeno, T., Ota, F., Ueno, M., Korekane, H., Takamatsu, S., Shirato, K., Matsumoto, A., Kobayashi, S., Yoshida, K., et al., 2012. Sensitivity of heterozygous a1,6-fucosyltransferase knock-out mice to cigarette smoke-induced emphysema:implication of aberrant transforming growth factor-b signaling and matrix metalloproteinase gene expression. J. Biol. Chem. 287, 16699-16708.

Gitlin, J.M., Homeister, J.W., Bulgrien, J., Counselman, J., Curtiss, L.K., Lowe, J.B., Boisvert, W.A., 2009. Disruption of tissue-specific fucosyltransferase VII, an enzyme necessary for selectin ligand synthesis, suppresses atherosclerosis in mice. Am. J. Pathol. 174, 343-350.

Hammerman, P.S., Sos, M.L., Ramos, A.H., Xu, C., Dutt, A., Zhou, W., Brace, L.E., Woods, B.A., Lin, W., Zhang, J., et al., 2011. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 1, 78-89.

He, J., Zou, Y., Liu, X., Zhu, J., Zhang, J., Zhang, R., Yang, T., Xia, H., 2018. Association of common genetic variants in pre-microRNAs and neuroblastoma susceptibility:a two-center study in Chinese children. Mol. Ther. Nucleic Acids 11, 1-8.

Herold, M.J., McPherson, K.G., Reichardt, H.M., 2006. Glucocorticoids in T cell apoptosis and function. Cell. Mol. Life Sci. 63, 60-72.

Hirsch, F.R., Scagliotti, G.V., Mulshine, J.L., Kwon, R., Curran Jr., W.J., Wu, Y.L., PazAres, L., 2017. Lung cancer:current therapies and new targeted treatments. Lancet 389, 299-311.

Hoque, M.O., Feng, Q., Toure, P., Dem, A., Critchlow, C.W., Hawes, S.E., Wood, T., Jeronimo, C., Rosenbaum, E., Stern, J., et al., 2006. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J. Clin. Oncol. 24, 4262-4269.

Horvath, S., Zhang, Y., Langfelder, P., Kahn, R.S., Boks, M.P., van Eijk, K., van den Berg, L.H., Ophoff, R.A., 2012. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol. 13, R97.

Irizarry, R.A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., Webster, M., et al., 2009. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissuespecific CpG island shores. Nat. Genet. 41, 178-186.

Judson, M.A., 2012. The treatment of pulmonary sarcoidosis. Respir. Med. 106, 1351-1361.

Kannagi, R., 2004. Molecular mechanism for cancer-associated induction of sialyl Lewis X and sialyl Lewis A expression-the Warburg effect revisited. Glycoconj. J. 20, 353-364.

Klinger, M., Farhan, H., Just, H., Drobny, H., Himmler, G., Loibner, H., Mudde, G.C., Freissmuth, M., Sexl, V., 2004. Antibodies directed against Lewis-Y antigen inhibit signaling of Lewis-Y modified ErbB receptors. Cancer Res. 64, 1087-1093.

Komatsu, H., Mizuguchi, S., Izumi, N., Chung, K., Hanada, S., Inoue, H., Suehiro, S., Nishiyama, N., 2013. Sialyl Lewis X as a predictor of skip N2 metastasis in clinical stage IA non-small cell lung cancer. World J. Surg. Oncol. 11, 309.

Kulasingam, V., Diamandis, E.P., 2008. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Nat. Clin. Pract. Oncol. 5, 588-599.

Laubli, H., Stevenson, J.L., Varki, A., Varki, N.M., Borsig, L., 2006. L-selectin facili- tation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res. 66, 1536-1542.

Li, D., Sun, H., Bai, G., Wang, W., Liu, M., Bao, Z., Li, J., Liu, H., 2018. a-1,3-Fucosyltransferase-VII siRNA inhibits the expression of SLex and hepatocarcinoma cell proliferation. Int. J. Mol. Med. 42, 2700-2708.

Liang, J.X., Gao, W., Cai, L., 2017. Fucosyltransferase VII promotes proliferation via the EGFR/AKT/mTOR pathway in A549 cells. OncoTargets Ther. 10, 3971-3978.

Liu, M., Zheng, Q., Chen, S., Liu, J., Li, S., 2021. FUT7 promotes the epithelialmesenchymal transition and immune infiltration in bladder urothelial carcinoma. J. Inflamm. Res. 14, 1069-1084.

Liu, Y.C., Yen, H.Y., Chen, C.Y., Chen, C.H., Cheng, P.F., Juan, Y.H., Chen, C.H., Khoo, K.H., Yu, C.J., Yang, P.C., et al., 2011. Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc. Natl. Acad. Sci. U. S. A. 108, 11332-11337.

Mizuguchi, S., Inoue, K., Iwata, T., Nishida, T., Izumi, N., Tsukioka, T., Nishiyama, N., Uenishi, T., Suehiro, S., 2006. High serum concentrations of Sialyl Lewisx predict multilevel N2 disease in non-small-cell lung cancer. Ann. Surg. Oncol. 13, 1010-1018.

Morgensztern, D., Waqar, S., Subramanian, J., Gao, F., Govindan, R., 2009. Improving survival for stage IV non-small cell lung cancer:a surveillance, epidemiology, and end results survey from 1990 to 2005. J. Thorac. Oncol. 4, 1524-1529.

Natsuka, S., Gersten, K.M., Zenita, K., Kannagi, R., Lowe, J.B., 1994. Molecular cloning of a cDNA encoding a novel human leukocyte alpha-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant. J. Biol. Chem. 269, 16789-16794.

Ponnampalam, A.P., Rogers, P.A., 2008. Expression and regulation of fucosyltransferase 4 in human endometrium. Reproduction 136, 117-123.

Qiao, R., Di, F., Wang, J., Wei, Y., Zhang, Y., Xu, T., Wang, Y., Gu, W., Han, B., Yang, R., 2020. The association between RAPSN methylation in peripheral blood and early stage lung cancer detected in case-control cohort. Cancer Manag. Res. 12, 11063-11075.

Qin, H., Liu, J., Yu, M., Wang, H., Thomas, A.M., Li, S., Yan, Q., Wang, L., 2020. FUT7 promotes the malignant transformation of follicular thyroid carcinoma through alpha1,3-fucosylation of EGF receptor. Exp. Cell Res. 393, 112095.

Raghu, V.K., Zhao, W., Pu, J., Leader, J.K., Wang, R., Herman, J., Yuan, J.M., Benos, P.V., Wilson, D.O., 2019. Feasibility of lung cancer prediction from lowdose CT scan and smoking factors using causal models. Thorax 74, 643-649.

Robertson, K.D., Wolffe, A.P., 2000. DNA methylation in health and disease. Nat. Rev. Genet. 1, 11-19.

Ryan, B.M., Robles, A.I., McClary, A.C., Haznadar, M., Bowman, E.D., Pine, S.R., Brown, D., Khan, M., Shiraishi, K., Kohno, T., et al., 2015. Identification of a functional SNP in the 3'UTR of CXCR2 that is associated with reduced risk of lung cancer. Cancer Res. 75, 566-575.

Satoh, H., Ishikawa, H., Kamma, H., Yamashita, Y.T., Takahashi, H., Ohtsuka, M., Hasegawa, S., 1998. Elevated serum sialyl Lewis X-i antigen levels in non-small cell lung cancer with lung metastasis. Respiration 65, 295-298.

Schabath, M.B., Cote, M.L., 2019. Cancer progress and priorities:lung cancer. Cancer Epidemiol. Biomarkers Prev. 28, 1563-1579.

Schutt, A.C., Bullington, W.M., Judson, M.A., 2010. Pharmacotherapy for pulmonary sarcoidosis:a Delphi consensus study. Respir. Med. 104, 717-723.

Shen, S.Y., Singhania, R., Fehringer, G., Chakravarthy, A., Roehrl, M.H.A., Chadwick, D., Zuzarte, P.C., Borgida, A., Wang, T.T., Li, T., et al., 2018. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 563, 579-583.

Springer, T.A., 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration:the multistep paradigm. Cell 76, 301-314.

Sun, S., Schiller, J.H., Gazdar, A.F., 2007. Lung cancer in never smokers-a different disease. Nat. Rev. Cancer 7, 778-790.

Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F., 2021. Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209-249.

Tan, D.S., Yom, S.S., Tsao, M.S., Pass, H.I., Kelly, K., Peled, N., Yung, R.C., Wistuba II, Yatabe, Y., Unger, M., et al., 2016. The international association for the study of lung cancer consensus statement on optimizing management of EGFR mutation-positive non-small cell lung cancer:status in 2016. J. Thorac. Oncol. 11, 946-963.

Torre, L.A., Bray, F., Siegel, R.L., Ferlay, J., Lortet-Tieulent, J., Jemal, A., 2015. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87-108.

Xu, T., Liu, J., Xia, Y., Wang, Z., Li, X., Gao, Q., 2021. Integrated analysis reveals the participation of IL4I1, ITGB7, and FUT7 in reshaping the TNBC immune microenvironment by targeting glycolysis. Ann. Med. 53, 916-928.

Xu, R.H., Wei, W., Krawczyk, M., Wang, W., Luo, H., Flagg, K., Yi, S., Shi, W., Quan, Q., Li, K., et al., 2017. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat. Mater. 16, 1155-1161.

Yang, R., Pfutze, K., Zucknick, M., Sutter, C., Wappenschmidt, B., Marme, F., Qu, B., Cuk, K., Engel, C., Schott, S., et al., 2015. DNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood. Int. J. Cancer 136, 1845-1855.

Zhang, Y., Schottker, B., Ordonez-Mena, J., Holleczek, B., Yang, R., Burwinkel, B., Butterbach, K., Brenner, H., 2015. F2RL3 methylation, lung cancer incidence and mortality. Int. J. Cancer 137, 1739-1748.

Zheng, R., Zhang, S., Zeng, H., Wang, S., Sun, K., Chen, R., Li, L., Wei, W., He, J., 2022. Cancer incidence and mortality in China, 2016. J. Natl. Cancer Center 2, 1-9.

Zhou, R., Llorente, C., Cao, J., Gao, B., Duan, Y., Jiang, L., Wang, Y., Kumar, V., 2020. Deficiency of intestinal a1-2-fucosylation exacerbates ethanol-induced liver disease in Mice. Alcohol Clin. Exp. Res. 44, 1842-1851.

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