Skip to main content

Advertisement

SpringerLink
Log in

Clinical significance of plasma anti-TOPO48 autoantibody and blood survivin-expressing circulating cancer cells in patients with early stage endometrial carcinoma

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To examine the clinical significance of an autoantibody (AAb) against a novel tumor-associated antigen (TAA) derived from human DNA-topoisomerase I, termed as TOPO48 AAb, and peripheral blood survivin-expressing circulating cells (CCC) in patients with early stage endometrial cancer (EC).

Methods

Blood samples were collected from 80 patients with early stage EC and 80 age-matched healthy subjects. Plasma levels of the TOPO48 AAb were measured with a specific antibody capture enzyme-linked immunosorbent assay (ELISA) and blood survivin-expressing CCC assessed with a reverse transcription-polymerase chain reaction products based on a hybridization-enzyme-linked immunosorbent assay (RT-PCR–ELISA). Sixty patients were followed up for 36 months after the initial assay test.

Results

There were 75% and 60% samples with positive levels of the TOPO48 AAb and survivin-expressing CCC in the cancer patients, respectively. However, the cumulative positive rate of combination of the two markers was increased to 93.3% with 0.927 (95% CI 0.871–0.984) of area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. During the follow-up period, patients with positive TOPO48 AAb but negative surviving-expressing CCC had a higher survival rate and a longer survival time than those with negative AAb but positive CCC (P = 0.01).

Conclusions

The combination of TOPO48 AAb and survivin-expressing CCC may be used as a novel recipe to improve the efficiency of early diagnosis and provide more accurate prognostic prediction in patients with early stage EC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. McAlpine JN, Temkin SM, Mackay HJ (2016) Endometrial cancer: not your grandmother’s cancer. Cancer 122:2787–2798

    Article  PubMed  Google Scholar 

  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132

    Article  Google Scholar 

  3. Carlson MJ, Thiel KW, Leslie KK (2014) Past, present, and future of hormonal therapy in recurrent endometrial cancer. Int J Womens Health 6:429–435

    PubMed  PubMed Central  Google Scholar 

  4. Creasman WT, Odicino F, Maisonneuve P et al (2006) Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological Cancer. Int J Gynaecol Obstet 95(1):105–143

    Article  Google Scholar 

  5. Reuschenbach M, von Knebel Doeberitz M, Wentzensen N (2009) A systematic review of humoral immune responses against tumor antigens. Cancer Immunol Immunother 58:1535–1544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Tang ZM, Ling ZG, Wang CM, Wu YB, Kong JL (2017) Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: a systematic review and meta-analysis. PLoS One 12:e0182117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Werner S, Chen H, Tao S, Brenner H (2015) Systematic review: serum autoantibodies in the early detection of gastric cancer. Int J Cancer 136:2243–2252

    Article  CAS  PubMed  Google Scholar 

  9. Lacombe J, Mangé A, Solassol J (2014) Use of autoantibodies to detect the onset of breast cancer. J Immunol Res 2014:574981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang H, Xia J, Wang K, Zhang J (2015) Serum autoantibodies in the early detection of esophageal cancer: a systematic review. Tumour Biol 36:95–109

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Yie SM, Ye SR, Ma XL, Xie K, Zhang JB, Cao M, He X, Hu ZB, Yang CL, Zhang J, Zhen J (2016) A protein fragment derived from DNA-topoisomerase I as a novel tumor associated antigen for the detection of early stage carcinoma. Br J Cancer 115:1555–1564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang JB, Cao M, Chen J, Ye SR, Xie K, He X, Ma XL, Zhang J, Yie SM (2018) Serum anti-TOPO48 autoantibody as a biomarker for early diagnosis and prognosis in patients with esophageal squamous cell carcinoma. Clin Res Hepatol Gastroenterol 42:276–284

    Article  CAS  PubMed  Google Scholar 

  14. Wu WB, Yie SM, Ye SR, Xie K, Zhang JB, Cao M, Chen J, He X, Ma XL, Zhang J (2018) An autoantibody against human DNA-topoisomerase I is a novel biomarker for non-small cell lung cancer. Ann Thorac Surg 105:1664–1670

    Article  PubMed  Google Scholar 

  15. Zhou L, Dicker DT, Matthew E, El-Deiry WS, Alpaugh RK (2017) Circulating tumor cells silent predictors of metastasis. Research 14:6

    Google Scholar 

  16. Lianidou ES, Markou A (2011) Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem 57:1242–1255

    Article  CAS  PubMed  Google Scholar 

  17. Bogani G, Liu MC, Dowdy SC, Cliby WA, Kerr SE, Kalli KR, Kipp BR, Halling KC, Campion MB, Mariani A (2015) Detection of circulating tumor cells in high-risk endometrial cancer. Anticancer Res 35:683–687

    PubMed  Google Scholar 

  18. Ni T, Sun X, Shan B, Wang J, Liu Y, Gu SL, Wang YD (2016) Detection of circulating tumour cells may add value in endometrial cancer management. Eur J Obstet Gynecol Reprod Biol 207:1–4

    Article  CAS  PubMed  Google Scholar 

  19. Yie SM, Luo B, Ye NY, Xie K, Ye SR (2006) Detection of survivin-expressing circulating cancer cells in the peripheral blood of breast cancer patients by a RT-PCR ELISA. Clin Exp Metastasis 23:279–289

    Article  CAS  PubMed  Google Scholar 

  20. Yie SM, Lou B, Ye SR, Cao M, He X, Li P, Hu K, Rao L, Wu SM, Xiao HB, Gao E (2008) Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse. Ann Surg Oncol 15:3073–3082

    Article  PubMed  Google Scholar 

  21. Yie SM, Lou B, Ye SR, He X, Cao M, Xie K, Ye NY, Lin R, Wu SM, Xiao HB, Gao E (2009) Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. Lung Cancer 63:284–290

    Article  PubMed  Google Scholar 

  22. Cao M, Yie SM, Wu SM, Chen S, Lou B, He X, Ye SR, Xie K, Rao L, Gao E, Ye NY (2009) Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance. Clin Exp Metastasis 26:751–758

    Article  CAS  PubMed  Google Scholar 

  23. Gradilone A, Petracca A, Nicolazzo C, Gianni W, Cortesi E, Naso G, Vincenzi B, Cristini C, De Berardinis E, Di Silverio F, Aglianò AM, Gazzaniga P (2010) Prognostic significance of survivin-expressing circulating tumour cells in T1G3 bladder cancer. BJU Int. 106:710–715

    Article  CAS  PubMed  Google Scholar 

  24. Ning Y, Hanna DL, Zhang W, Mendez A, Yang D, El-Khoueiry R, Matsusaka S, Sunakawa Y, Stremitzer S, Parekh A, Okazaki S, Berger MD, Barzi A, Lenz HJ (2015) Cytokeratin-20 and Survivin-Expressing Circulating Tumor Cells Predict Survival in Metastatic Colorectal Cancer Patients by a Combined Immunomagnetic qRT-PCR Approach. Mol Cancer Ther 14:2401–2408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cao W, Yang W, Li H, Lou G, Jiang J, Geng M, Xi W, Ren R, Qu Q, Jin X, Zhu Y, Jin Y (2011) Using detection of survivin-expressing circulating tumor cells in peripheral blood to predict tumor recurrence following curative resection of gastric cancer. J Surg Oncol 103:110–115

    Article  PubMed  Google Scholar 

  26. Steinbakk A, Malpica A, Slewa A, Skaland I, Gudlaugsson E, Janssen EA, Løvslett K, Fiane B, Kruse AJ, Feng W, Yinhua Y, Baak JP (2011) Biomarkers and microsatellite instability analysis of curettings can predict the behavior of FIGO stage I endometrial endometrioid adenocarcinoma. Mod Pathol 24:1262–1271

    Article  PubMed  Google Scholar 

  27. Ambrosini G, Adida C, Altieri D (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921

    Article  CAS  Google Scholar 

  28. Yilmaz E, Koyuncuoglu M, Görken IB, Okyay E, Saatli B, Ulukus EC, Saygili U (2011) Expression of matrix metalloproteinase-2 and survivin in endometrioid and nonendometrioid endometrial cancers and clinicopathologic significance. J Gynecol Oncol 22:89–96

    Article  PubMed  PubMed Central  Google Scholar 

  29. Brunner A, Riss P, Heinze G, Brustmann H (2012) pHH3 and survivin are co-expressed in high-risk endometrial cancer and are prognostic relevant. Br J Cancer 107:84–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sorosky JI (2008) Endometrial cancer. Obstet Gynecol 111:436–447

    Article  PubMed  Google Scholar 

  31. Wilczyński M, Danielska J, Wilczyński J (2016) An update of the classical Bokhman’s dualistic model of endometrial cancer. Prz Menopauzalny. 15:63–68

    PubMed  PubMed Central  Google Scholar 

  32. Suh DH, Kim JW, Kang S, Kim HJ, Lee KH (2014) Major clinical research advances in gynecologic cancer in 2013. J Gynecol Oncol 25:236–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was partially supported by Grant no. KJXM20030826 from the Research and Development Program of the Chengdu Technology Bureau, Chengdu, China, and partly supported by Sichuan Science and Technology Program (Grant no. 2018SZ0144,2016SZ0066, 2018SZ0284 and 2018FZ0043) and West China Second University Hospital of Sichuan University (Grant no. kx027).

Author information

Author notes

  1. Xiao-hui Jiang, Zou-ying Yao and Xu He the three authors contributed equally to this study.

Authors and Affiliations

  1. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Human Sperm Bank, West China Second University Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China

    Xiao-hui Jiang

  2. Department of Traditional Chinese Medicine, Lishui Central Hospital, Lishui, 323000, Zhejiang, People’s Republic of China

    Zou-ying Yao

  3. Core Laboratory, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, People’s Republic of China

    Xu He, Jian-bo Zhang, Jie Chen & Mei Cao

  4. Department of Oncology, Sichuan Academy of Medical Sciences Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, People’s Republic of China

    Ke Xie

  5. Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, Sichuan, People’s Republic of China

    Jian Zhang

  6. Chengdu Cancer Bioengineering Research Institute, 37 Twelve Bridge Road, Chengdu, 610048, Sichuan, People’s Republic of China

    Shang-mian Yie

Authors
  1. Xiao-hui Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zou-ying Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xu He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jian-bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ke Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mei Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shang-mian Yie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XHJ, ZYY and XH: data collection, experimental performs, data analysis, manuscript draft writing; KX and JZ: clinical patients and control support; JBZ, JC and MC: experimental support; SMY, project development, data collection, manuscript writing and review

Corresponding author

Correspondence to Shang-mian Yie.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving were in accordance with the ethical standards of the institutional research committee of the Sichuan Provincial People’s Hospital (No. 20070126,) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Availability of data and materials

We have full control of all primary data and that we agree to allow the Journal to review our data if requested.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Xh., Yao, Zy., He, X. et al. Clinical significance of plasma anti-TOPO48 autoantibody and blood survivin-expressing circulating cancer cells in patients with early stage endometrial carcinoma. Arch Gynecol Obstet 299, 229–237 (2019). https://doi.org/10.1007/s00404-018-4938-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-018-4938-7

Keywords

Search

Navigation