nach oben

International Journal of Clinical Oncology

Erschienen in:

01.10.2015 | Original Article

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

verfasst von: Shuang Xu, Mingmei Huangfu, Xueli Jia, Xiaowei Song, Baosheng Sun, Kuang-Hui Lee, Linlin Liu, Shilong Sun

Erschienen in: International Journal of Clinical Oncology | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

Overexpression of tumor-associated antigens has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was designed to test whether circulating antibody to FOXP3 protein-derived antigens was altered in early cervical cancer and cervical benign tumors.

Methods

A total of 141 patients with cervical cancer, 133 patients with cervical benign tumors and 148 healthy age-matched volunteers were recruited. The level of circulating anti-FOXP3 IgG antibody was tested using an enzyme-linked immunosorbent assay developed in-house with linear peptide antigens derived from FOXP3 protein. The linear peptide antigens were designed according to the computational prediction of HLA-II epitopes.

Results

Student’s t test showed that anti-FOXP3 IgG in the malignant tumor group and the benign tumor group was significantly higher than in the control group (t = 6.127, p < 0.001; t = 2.704, p = 0.007). In addition, patients with stage I cervical cancer (t = 2.968, p = 0.003) had a significantly higher level of FOXP3 autoantibodies than patients with benign tumors. The sensitivity against >90 % specificity was 20.6 % with an interassay deviation of 11.7 % in the cervical cancer group. Based on a cut-off value determined by the 98th percentile of the control group IgG levels, the anti-FOXP3 IgG positivity was 2.1 % in patients with cervical cancer compared to 2.0 % in the health controls (chi-squared = 0.004, p = 0.952, OR = 1.051, 95 % CI 0.209–5.295).

Conclusion

The circulating autoantibody to FOXP3 reflecting the continuous development of the cervical lesion, may be a potential biomarker with early prognostic values for cervical cancer.

Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108CrossRefPubMed

Yanan Wu (2009) The screening methods of cervical carcinoma at early stage. J Liaoning University Traditional Chin Med 11(6):65–67

Anderson KS, LaBaer J (2005) The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res 4(4):1123–1133PubMedCentralCrossRefPubMed

Zaenker P, Ziman MR (2013) Serologic autoantibodies as diagnostic cancer biomarkers—a review. Cancer Epidemiol Biomarkers Prev 22(12):2161–2181CrossRefPubMed

Coffer PJ, Burgering BM (2004) Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol 4(11):889–899CrossRefPubMed

Fontenot JD, Rasmussen JP, Williams LM et al (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3):329–341CrossRefPubMed

Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061CrossRefPubMed

Whiteside TL (2014) Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol Immunother 63(1):67–72PubMedCentralCrossRefPubMed

Wolf AM, Wolf D, Steurer M et al (2003) Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 9(2):606–612PubMed

10.

Woo EY, Chu CS, Goletz TJ et al (2001) Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61(12):4766–4772PubMed

11.

Liu L, Liu N, Liu B et al (2012) Are circulating autoantibodies to ABCC3 transporter a potential biomarker for lung cancer? J Cancer Res Clin Oncol 138(10):1737–1742CrossRefPubMed

12.

Cheng Y, Xu J, Guo J et al (2013) Circulating autoantibody to ABCC3 may be a potential biomarker for esophageal squamous cell carcinoma. Clin Transl Oncol 15(5):398–402CrossRefPubMed

13.

Zhang C, Ye L, Guan S et al (2014) Autoantibodies against p16 protein-derived peptides may be a potential biomarker for non-small cell lung cancer. Tumour Biol 35(3):2047–2051CrossRefPubMed

14.

Jin Y, Guan S, Liu L et al (2014) Anti-p16 autoantibodies may be a useful biomarker for early diagnosis of esophageal cancer. Asia Pac J Clin Oncol. doi:10.1111/ajco.12198

15.

Wang W, Guan S, Sun S et al (2014) Detection of circulating antibodies to linear peptide antigens derived from ANXA1 and DDX53 in lung cancer. Tumor Biol 35(5):4901–4905CrossRef

16.

Ye L, Guan S, Zhang C et al (2013) Circulating autoantibody to FOXP3 may be a potential biomarker for esophageal squamous cell carcinoma. Tumour Biol 34(3):1873–1877CrossRefPubMed

17.

Cunha LL, Morari EC, Nonogaki S et al (2012) Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas. Clinics (Sao Paulo) 67(5):483–488CrossRef

18.

Tan EM, Zhang J (2008) Autoantibodies to tumor-associated antigens: reporters from the immune system. Immunol Rev 222:328–340PubMedCentralCrossRefPubMed

19.

Wang LH, Su L, Wang JT (2010) Correlation between elevated FOXP3 expression and increased lymph node metastasis of gastric cancer. Chin Med J (Engl) 123(24):3545–3549

20.

Niu J, Jiang C, Li C et al (2011) Foxp3 expression in melanoma cells as a possible mechanism of resistance to immune destruction. Cancer Immunol Immunother 60(8):1109–1118CrossRefPubMed

21.

Tan HT, Low J, Lim SG et al (2009) Serum autoantibodies as biomarkers for early cancer detection. FEBS J 276(23):6880–6904CrossRefPubMed

22.

Chen H, Werner S, Tao S et al (2014) Blood autoantibodies against tumor-associated antigens as biomarkers in early detection of colorectal cancer. Cancer Lett 346(2):178–187CrossRefPubMed

23.

Werner S, Chen H, Tao S et al (2014) Systematic review: serum autoantibodies in the early detection of gastric cancer. Int J Cancer. doi:10.1002/ijc.28807

24.

Erfani N, Hamedi-Shahraki M, Rezaeifard S et al (2014) FoxP3+ regulatory T cells in peripheral blood of patients with epithelial ovarian cancer. Iran J Immunol 11(2):105–112PubMed

25.

Hanakawa H, Orita Y, Sato Y et al (2014) Regulatory T-cell infiltration in tongue squamous cell carcinoma. Acta Otolaryngol 134(8):859–864CrossRefPubMed

26.

Azzimonti B, Zavattaro E, Provasi M et al (2015) Intense Foxp3+ CD25+ regulatory T cell infiltration is associated with high-grade cutaneous squamous cell carcinoma and counterbalanced by CD8+ /Foxp3+ CD25+ ratio. Br J Dermatol 172(1):64–73CrossRefPubMed

27.

Shibuya KC, Goel VK, Xiong W et al (2014) Pancreatic ductal adenocarcinoma contains an effector and regulatory immune cell infiltrate that is altered by multimodal neoadjuvant treatment. PLoS One 9(5):e96565PubMedCentralCrossRefPubMed

28.

Kim S, Lee A, Lim W et al (2014) Zonal difference and prognostic significance of FOXP3 regulatory T cell infiltration in breast cancer. J Breast Cancer 17(1):8–17PubMedCentralCrossRefPubMed

29.

Raghavan S, Quiding-Järbrink M (2011) Regulatory T cells in gastrointestinal tumors. Expert Rev Gastroenterol Hepatol 5(4):489–501CrossRefPubMed

30.

Merlo A, Casalini P, Carcangiu ML et al (2009) FOXP3 expression and overall survival in breast cancer. J Clin Oncol 27(11):1746–1752CrossRefPubMed

31.

Wolf AM, Rumpold H, Wolf D et al (2007) Role of forkhead box protein 3 expression in invasive breast cancer. J Clin Oncol 25(28):4499–4500CrossRefPubMed

32.

Hou F, Li Z, Ma D et al (2012) Distribution of Th17 cells and Foxp3-expressing T cells in tumor-infiltrating lymphocytes in patients with uterine cervical cancer. Clin Chim Acta 413(23–24):1848–1854CrossRefPubMed

33.

Jaafar F, Righi E, Lindstrom V et al (2009) Correlation of CXCL12 expression and FoxP3+ cell infiltration with human papillomavirus infection and clinicopathological progression of cervical cancer. Am J Pathol 175(4):1525–1535PubMedCentralCrossRefPubMed

34.

Loddenkemper C, Hoffmann C, Stanke J et al (2009) Regulatory (FOXP3+) T cells as target for immune therapy of cervical intraepithelial neoplasia and cervical cancer. Cancer Sci 100(6):1112–1117CrossRefPubMed

35.

Scott ME, Ma Y, Kuzmich L et al (2009) Diminished IFN-gamma and IL-10 and elevated FOXP3 mRNA expression in the cervix are associated with CIN 2 or 3. Int J Cancer 124(6):1379–1383PubMedCentralCrossRefPubMed

36.

Zeng C, Yao Y, Jie W et al (2013) Up-regulation of Foxp3 participates in progression of cervical cancer. Cancer Immunol Immunother 62(3):481–487CrossRefPubMed

37.

Caron M, Choquet-Kastylevsky G, Joubert-Caron R (2007) Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics 6(7):1115–1122CrossRefPubMed

38.

Chapman CJ, Healey GF, Murray A et al (2012) Early CDT^®-Lung test: improved clinical utility through additional autoantibody assays. Tumour Biol 33(5):1319–1326PubMedCentralCrossRefPubMed

Titel: FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer
verfasst von: Shuang Xu
Mingmei Huangfu
Xueli Jia
Xiaowei Song
Baosheng Sun
Kuang-Hui Lee
Linlin Liu
Shilong Sun
Publikationsdatum: 01.10.2015
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 5/2015
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-015-0797-4

Neu im Fachgebiet Onkologie

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

23.05.2024 Leitsymptome in der Hausarztpraxis Nachrichten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer