Skip to main content

Advertisement

Log in

Fucosylation genes as circulating biomarkers for lung cancer

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Fucosyltransferases (FUTs) catalyze fucosylation, which plays a central role in biological processes. Aberrant fucosylation is associated with malignant transformation. Here we investigated whether transcriptional levels of genes coding the FUTs in plasma could provide cell-free circulating biomarkers for lung cancer.

Methods

mRNA expression of all 13 Futs (Fut1-11, Pofut1, and Pofut2) was evaluated by PCR assay in 48 lung tumor tissues and the 48 matched noncancerous lung tissues, and plasma of 64 lung cancer patients and 32 cancer-free individuals to develop plasma Fut biomarkers. The developed plasma Fut biomarkers were validated in an independent cohort of 40 lung cancer patients and 20 controls for their diagnostic performance.

Results

Four of the 13 Futs showed a different transcriptional level in 48 lung tumor tissues compared with the 48 matched nonconscious tissues (all < 0.05). Two (Fut8, and Pofut1) of the four Futs had a higher plasma level in 64 lung cancer patients compared with 32 control subjects, and consistent with that in lung tissue specimens. Combined analysis of the two Futs produced 81% sensitivity and 86% specificity for diagnosis of lung cancer, and was independent of stage and histology of lung tumors. The diagnostic performance of the two plasma biomarkers was successfully validated in the different cohort of 40 lung cancer patients and 20 control individuals.

Conclusion

The fucosylation genes may provide new circulating biomarkers for the early detection of lung cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aberle DR, Adams AM, Berg CD et al (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409

    Article  Google Scholar 

  • American Cancer Society (2018) Cancer facts and figures. American Cancer Society, New York

    Google Scholar 

  • Anjuman N, Li N, Guarnera M, Stass SA, Jiang F (2013) Evaluation of lung flute in sputum samples for molecular analysis of lung cancer. Clin Transl Med 2(1):15

    Article  Google Scholar 

  • Aoyagi Y, Suzuki Y, Igarashi K et al (1991) The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver. Cancer 67(9):2390–2394

    Article  CAS  Google Scholar 

  • Bibbins-Domingo K, Grossman DC, Curry SJ et al (2017) Folic acid supplementation for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement. JAMA 317(2):183–189

    Article  Google Scholar 

  • Breborowicz J, Mackiewicz A, Breborowicz D (1981) Microheterogeneity of alpha-fetoprotein in patient serum as demonstrated by lectin affino-electrophoresis. Scand J Immunol 14(1):15–20

    Article  CAS  Google Scholar 

  • Cancer Facts & Figures (2012) American Cancer Society (ACS). J Consumer Health Internet 16(3):366–367

    Article  Google Scholar 

  • Chachadi VB, Bhat G, Cheng PW (2015) Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands. Glycobiology 25(9):963–975

    Article  CAS  Google Scholar 

  • Chen CY, Jan YH, Juan YH et al (2013) Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer. Proc Natl Acad Sci USA 110(2):630–635

    Article  CAS  Google Scholar 

  • Dodd LE, Pepe MS (2003) Partial AUC estimation and regression. Biometrics 59(3):614–623

    Article  Google Scholar 

  • Dong S, Wang Z, Huang B, Zhang J, Ge Y, Fan Q (2017) Bioinformatics insight into glycosyltransferase gene expression in gastric cancer: POFUT1 is a potential biomarker. Biochem Biophys Res Commun 483(1):171–177

    Article  CAS  Google Scholar 

  • Honma R, Kinoshita I, Miyoshi E et al (2015) Expression of fucosyltransferase 8 is associated with an unfavorable clinical outcome in non-small cell lung cancers. Oncology 88(5):298–308

    Article  CAS  Google Scholar 

  • Hubers AJ, Prinsen CF, Sozzi G, Witte BI, Thunnissen E (2013a) Molecular sputum analysis for the diagnosis of lung cancer. Br J Cancer 109(3):530–537

    Article  CAS  Google Scholar 

  • Hubers AJ, Heideman DA, Yatabe Y et al (2013b) EGFR mutation analysis in sputum of lung cancer patients: a multitechnique study. Lung Cancer 82(1):38–43

    Article  Google Scholar 

  • Humphrey LL, Deffebach M, Pappas M et al (2013) Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med 159(6):411–420

    Article  Google Scholar 

  • Jiang F, Todd NW, Qiu Q, Liu Z, Katz RL, Stass SA (2009) Combined genetic analysis of sputum and computed tomography for noninvasive diagnosis of non-small-cell lung cancer. Lung Cancer 66(1):58–63

    Article  Google Scholar 

  • Jiang F, Todd NW, Li R, Zhang H, Fang H, Stass SA (2010) A panel of sputum-based genomic marker for early detection of lung cancer. Cancer Prev Res (Phila) 3(12):1571–1578

    Article  Google Scholar 

  • Li N, Ma J, Guarnera MA, Fang H, Cai L, Jiang F (2014) Digital PCR quantification of miRNAs in sputum for diagnosis of lung cancer. J Cancer Res Clin Oncol 140(1):145–150

    Article  CAS  Google Scholar 

  • Loriol C, Audfray A, Dupuy F, Germot A, Maftah A (2007) The two N-glycans present on bovine Pofut1 are differently involved in its solubility and activity. FEBS J 274(5):1202–1211

    Article  CAS  Google Scholar 

  • Ma J, Jemal A, Smith R (2013a) Reply to lung cancer deaths averted by screening should be considered in the context of tobacco control policies. Cancer 119(18):3420–3421

    Article  Google Scholar 

  • Ma J, Li N, Guarnera M, Jiang F (2013b) Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights 8:127–136

    Article  CAS  Google Scholar 

  • Ma J, Mannoor K, Gao L et al (2014) Characterization of microRNA transcriptome in lung cancer by next-generation deep sequencing. Mol Oncol 8(7):1208–1219

    Article  CAS  Google Scholar 

  • Ma L, Dong P, Liu L et al (2016) Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. Biochem Biophys Res Commun 473(2):503–510

    Article  CAS  Google Scholar 

  • Marks JR, Anderson KS, Engstrom P et al (2015) Construction and analysis of the NCI-EDRN breast cancer reference set for circulating markers of disease. Cancer Epidemiol Biomark Prev 24(2):435–441

    Article  CAS  Google Scholar 

  • Moyer VA (2014) Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 160(5):330–338

    Article  Google Scholar 

  • Nolen BM, Lomakin A, Marrangoni A, Velikokhatnaya L, Prosser D, Lokshin AE (2015) Urinary protein biomarkers in the early detection of lung cancer. Cancer Prev Res (Phila) 8(2):111–119

    Article  CAS  Google Scholar 

  • Patz EF Jr, Pinsky P, Gatsonis C et al (2014) Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med 174(2):269–274

    Article  Google Scholar 

  • Shen J, Liu Z, Todd NW et al (2011) Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer 11:374

    Article  CAS  Google Scholar 

  • Shen J, Liao J, Guarnera MA et al (2014) Analysis of MicroRNAs in sputum to improve computed tomography for lung cancer diagnosis. J Thorac Oncol 9(1):33–40

    Article  CAS  Google Scholar 

  • Stahl M, Uemura K, Ge C, Shi S, Tashima Y, Stanley P (2008) Roles of Pofut1 and O-fucose in mammalian Notch signaling. J Biol Chem 283(20):13638–13651

    Article  CAS  Google Scholar 

  • Su Y, Fang H, Jiang F (2016a) Integrating DNA methylation and microRNA biomarkers in sputum for lung cancer detection. Clin Epigenet 8:109

    Article  Google Scholar 

  • Su J, Liao J, Gao L et al (2016b) Analysis of small nucleolar RNAs in sputum for lung cancer diagnosis. Oncotarget 7(5):5131–5142

    Article  Google Scholar 

  • Sullivan FX, Kumar R, Kriz R et al (1998) Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. J Biol Chem 273(14):8193–8202

    Article  CAS  Google Scholar 

  • Taniguchi N, Kizuka Y (2015) Glycans and cancer: role of N-glycans in cancer biomarker, progression and metastasis, and therapeutics. Adv Cancer Res 126:11–51

    Article  Google Scholar 

  • Travis WD (2014) The 2015 WHO classification of lung tumors. Pathologe 35(Suppl 2):188

    Article  Google Scholar 

  • Tuck MK, Chan DW, Chia D et al (2009) Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res 8(1):113–117

    Article  CAS  Google Scholar 

  • Wan G, Tian L, Yu Y et al (2017) Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer. Biochem Biophys Res Commun 491(1):104–111

    Article  CAS  Google Scholar 

  • Wu LH, Shi BZ, Zhao QL, Wu XZ (2010) Fucosylated glycan inhibition of human hepatocellular carcinoma cell migration through binding to chemokine receptors. Glycobiology 20(2):215–223

    Article  CAS  Google Scholar 

  • Xie Y, Todd NW, Liu Z et al (2010) Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer 67(2):170–176

    Article  Google Scholar 

  • Xing L, Todd NW, Yu L, Fang H, Jiang F (2010) Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers. Mod Pathol 23(8):1157–1164

    Article  CAS  Google Scholar 

  • Xing L, Su J, Guarnera MA et al (2015) Sputum microRNA biomarkers for identifying lung cancer in indeterminate solitary pulmonary nodules. Clin Cancer Res 21(2):484–489

    Article  CAS  Google Scholar 

  • Yu L, Todd NW, Xing L et al (2010) Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer 127(12):2870–2878

    Article  CAS  Google Scholar 

  • Zhou W, Ma H, Deng G, Tang L, Lu J, Chen X (2017) Clinical significance and biological function of fucosyltransferase 2 in lung adenocarcinoma. Oncotarget 8(57):97246–97259

    Article  Google Scholar 

Download references

Funding

This work was supported in part by NCI R21CA205746, VA Merit Award I01 CX000512, Award from the Geaton and JoAnn DeCesaris Family Foundation, and Maryland Innovation Initiative (MII) Commercialization Program-Phase 1/2 Grant (F.J.)

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Feng Jiang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

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. This article does not contain any studies with animals performed by any of the authors. All participants were provided with information about the research project that was understandable and that permitted them to make an informed and voluntary decision about whether or not to participate.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary table 1. Primers and probes of 13 Futs (XLSX 10 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leng, Q., Tsou, JH., Zhan, M. et al. Fucosylation genes as circulating biomarkers for lung cancer. J Cancer Res Clin Oncol 144, 2109–2115 (2018). https://doi.org/10.1007/s00432-018-2735-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-018-2735-0

Keywords

Navigation