Article Data

  • Views 599
  • Dowloads 122

Original Research

Open Access

Forkhead box protein 3 (FoxP3) mRNA as a diagnostic marker in ovarian tumors: a pilot study

  • N.H. Abdel-Hay1
  • A.A. Mansour1
  • M.A. El Sherbini1,*,
  • F.I. Abdel Motaleb1
  • A.H. El-Shalakany2

1Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Abbasia, Egypt

2Gynecologic Oncology Unit, Ain Shams University Maternity Hospital, Cairo, Abbasia, Egypt

DOI: 10.12892/ejgo3470.2017 Vol.38,Issue 2,April 2017 pp.251-256

Published: 10 April 2017

*Corresponding Author(s): M.A. El Sherbini E-mail: me_sherbini@yahoo.com

Abstract

Purpose: To assess the diagnostic performance of forkhead box protein 3 (FoxP3) mRNA in ovarian tumors. Materials and Methods: Using quantitative real time reverse transcription PCR (q-RT-PCR), FoxP3 mRNA level was measured in fresh frozen ovarian tumors and its diagnostic performance was compared to those of preoperative serum CA125 and risk of malignancy index (RMI). Results: FoxP3 mRNA was differentially expressed in the malignant (n = 25) and benign (n = 25) groups, yet without statistically significant differences; positivity rate: 15/25 vs. 10/25; p = 0.157, median: 0.429 vs. 0.046; p = 0.684, and mean ± SD: 73.75 ± 234.68 vs. 247.09 ± 792.17; p = 0.301. Although it showed much less diagnostic performance (AUC: 0.534), FoxP3 mRNA enhanced the diagnostic sensitivity and specificity of both CA125 and RMI (96% and 100%, for both). Conclusion: FoxP3 mRNA may not be good diagnostic marker in ovarian tumors; however it may prove valuable in defining underlying tumor molecular signature.

Keywords

Ovarian tumor; q-RT-PCR; FoxP3 mRNA; CA125; Treg.


Cite and Share

N.H. Abdel-Hay,A.A. Mansour,M.A. El Sherbini,F.I. Abdel Motaleb,A.H. El-Shalakany. Forkhead box protein 3 (FoxP3) mRNA as a diagnostic marker in ovarian tumors: a pilot study. European Journal of Gynaecological Oncology. 2017. 38(2);251-256.

References

[1] Cannistra S.A., Gershenson D.M., Recht A.: “Ovarian cancer, fallopian tube carcinoma, and peritoneal carcinoma”. In: DeVita V.T., Hellman, and Rosenberg’s Cancer (9th ed). Principles and Practice of Oncology. Philadelphia, PA, USA: Lippincott, Williams, & Wilkins, 2011, 1368.

[2] Jemal A., Siegel R., Ward E., Hao Y., Xu J., Thun M.J.: “Cancer statistics”. CA Cancer J. Clin., 2009; 59, 225.

[3] McGuire W.P.: “Maintenance therapy for ovarian cancer: of Helsinki and Hippocrates”. J. Clin. Oncol., 2009, 27, 4633.

[4] Coleman M.P., Forman D., Bryant H., Butler J., Rachet B., Maringe C., et al.: “Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data”. Lancet, 2011, 377, 127.

[5] Yamamoto Y., Yamada R., Oguri H., Maeda N., Fukaya T.: “Comparison of four malignancy risk indices in the preoperative evaluation of patients with pelvic masses”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2009, 144, 163.

[6] Wang L., Liu R., Ribick M., Zheng P., Liu Y.: “FOXP3 as an Xlinked tumor suppressor”. Discov. Med., 2010, 10, 322.

[7] Hori S, Sakaguchi S.: “Foxp3: a critical regulator of the development and function of regulatory T cells”. Microbes Infect., 2004, 6, 745.

[8] Hinz S., Pagerlos-raluy L., Oberg H.-H., Ammerpohl O., Grussel S., Sipos B., et al.: “Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer”. Cancer Res., 2007, 67(17), 8344.

[9] Karanikas V., Speletas M., Zamanakou M., Kalala F., Loules G., Kerenidi T., et al.: “Foxp3 expression in human cancer cells”. J. Transl. Med., 2008, 22, 6.

[10] Gratz I.K., Campbell D.J.: “Organ-specific and memory treg cells: specificity, development, function, and maintenance”. Front. Immunol., 2014, 5, 333.

[11] Zhang H.Y., Sun H.: “Up-regulation of Foxp3 inhibits cell proliferation, migration and invasion in epithelial ovarian cancer”. Cancer Lett., 2010, 287, 91.

[12] Knol A.C., Nguyen J.M., Quéreux G., Brocard A., Khammari A., Dréno B.: “Prognostic value of tumor-infiltrating Foxp3+ T-cell subpopulations in metastatic melanoma”. Exp. Dermatol., 2011, 20, 430.

[13] Preston C.C., Maurer M.J., Oberg A.L., Visscher D.W., Kalli K.R., Hartmann L.C., et al.: “The ratios of Cd8+ T cells to CD4+CD25+FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer”. PLoS One, 2013, 8, e80063.

[14] Haque M., Fino K., Lei F., Xiong X., Song J.: “Utilizing regulatory T cells against rheumatoid arthritis”. Front. Oncol., 2014, 4, 209.

[15] Jones K.R., Kang E.M.: “Graft versus host disease: New insights into A2A receptor agonist therapy”. Comput. Struc.t Biotechnol. J., 2014, 13, 101.

[16] Cannon M.J., Goyne H.E., Stone P.J., Macdonald L.J., James L.E., Cobos E., Chiriva-Interanti M.: “Modulation of p38 MAPK signaling enhances dendritic cell activation of human CD4+ Th17 responses to ovarian tumor antigen”. Cancer Immunol. Immunother., 2013, 62, 839.

[17] Jacobs I., Oram D., Fairbanks J., Turner J., Frost C., Grudzinskas J.G.: “A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer”. Br. J. Obstet. Gynaecol., 1990, 97, 922.

[18] AJCC. American Joint Committee on Cancer (2010): “Ovary and Primary Peritoneal Carcinoma”. In: AJCC Cancer Staging Manual (7th ed). New York: Springer, 2010, 419.

[19] Rutella S., Bonanno G., Procoli A., Mariotti A., de Ritis D.G., Curti A., et al.: “Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features”. Blood, 2006, 108, 218.

[20] Smith S.D., Wheeler M.A., Plescia J., Colberg J.W., Weiss R.M., Altieri D.C.: “Urine detection of survivin and diagnosis of bladder cancer”. JAMA, 2001, 285(3), 324.

[21] Motz G.T., Santoro S.P., Wang L.P., Garrabrant T., Lastra R.R., Hagemann I.S., et al.: “Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors”. Nat. Med., 2014, 20, 607.

[22] Erfani N., Hamedi-Shahraki M., Rezaeifard S., Haghshenas M., Rasouli M., Samsami Dehaghani A. “FoxP3+ regulatory T cells in peripheral blood of patients with epithelial ovarian cancer”. Iran J. Immunol., 2014, 11, 105.

[23] deLeeuw R.J., Kroeger D.R., Kost S.E., Chang P.P., Webb J.R., Nelson B.H.: “CD25 identfies a subset of CD4+FoxP- TIL that are exhausted yet prognostically favorable in human ovarian cancer”. Cancer Immunol. Res., 2015, 3, 245.

[24] Wicherek L., Jozwicki W., Windorbska W., Roszkowski K., Lukaszewska E., Wisniewski M., et al.: “Analysis of treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer – a preliminary report”. Am. J. Reprod. Immunol., 2001, 66, 444.

[25] Hennessy B.T., Coleman R.L., Markman M.: “Ovarian cancer”. Lancet, 2009, 374, 1371.

[26] Van Gorp T., Cadron I., Despierre E., Daemen A., Leunen K., Amant F., et al.: “HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm”. Br. J. Cancer, 2011, 104, 863.

[27] Bouzari Z., Yazdani S., Ahmadi M.H., Barat S., Kelagar Z.S., Kutenaie M.J., et al.: “Comparison of three malignancy risk indices and CA-125 in the preoperative evaluation of patients with pelvic masses”. MBC Res. Notes, 2011, 4, 206.

[28] Van den Akker P.A., Aalders A.L., Snijders M.P., Kluivers K.B., Samlal R.A., Vollebergh J.H., Massuger L.F.: “Evaluation of the Risk of Malignancy Index in daily clinical management of adnexal masses”. Gynecol. Oncol., 2010, 116, 384.

[29] El Sherbini M.A., Sallam M.M., Shaban E.A., El-Shalakany A.H.: “Diagnostic value of serum kallikrein-related peptidases 6 and 10 versus CA125 in ovarian cancer”. Int. J. Gynecol. Cancer, 2011, 21, 625.

[30] Chang W.J., Du Y., Zhao X., Ma L.Y., Cao G.W.: “Inflammation-related factors predicting prognosis of gastric cancer”. World J. Gastroenterol., 2014, 20, 4586.

[31] Horn T., Laus J., Seitz A.K., Maurer T., Schmied S.C., Wolf P. et al.: “The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer”. World J. Urol., 2016, 34, 181.

[32] Curiel T.J., Coukos G., Zou L., Alvarez X., Cheng P., Mottram P., et al.: “Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival”. Nature Med., 2004, 10, 942.

[33] Wolf D., Wolf A.M., Rumpold H., Fiegel H., Zeimet A.C., Muller- Holzner E., et al.: “The expression of the regulatory T cell-specific forkhead box protein transcription factor Foxp3 is associated with poor prognosis in ovarian cancer”. Clin. Cancer Res., 2005, 11, 8326.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top