Serum concentrations of S100–A11 and AIF-1 are elevated in cervical cancer patients with lymph node involvement

Czech version

Authors: Maděrka M. ¹; Dvořák V. ²; Hambálek J. ¹; Stejskal D. ^3,4; Krejčí G. ³; Švesták M. ³; Langová K. ⁵; Pilka R. ¹
Authors‘ workplace: Porodnicko-gynekologická klinika LF UP a FN Olomouc ¹; Centrum ambulantní gynekologie a primární péče, Brno ²; Oddělení laboratorní medicíny, AGEL Středomoravská nemocniční, a. s., Prostějov ³; Ústav laboratorní diagnostiky, FN Ostrava ⁴; Ústav lékařské biofyziky, LF UP v Olomouci ⁵
Published in: Ceska Gynekol 2021; 86(1): 17-21
Category: Original Article
doi: https://doi.org/10.48095/cccg202117

Overview

Objective: The aim of this study was to compare the serum levels of TFF3, AIF-1, S100–A11 and DKK1 in surgically staged patients with cervical cancer, and in healthy female controls.

Methods: In total 85 consecutive patients diagnosed at the Department of Obstetrics and Gynecology, University Hospital in Olomouc with cervical cancer undergoing radical hysterectomy or fertility sparing surgery with pelvic lymphadenectomy were included. Ninety patients who underwent elective total hysterectomy for nonmalignant disorder represented a control group. In all patients, preoperative serum samples were taken and separated; the sera were all stored at –80 °C until analysis for TFF3, AIF-1, S100–A11 and DKK1.

Results: According to the final histopathological examination, 32 (40.5%) out of 79 cervical cancer patients with microscopically examined lymph nodes were lymph node-positive. S100–A11 (P < 0.0001) and AIF-1 levels (P < 0.0001) were higher in cervical cancer patients than in controls. Furthermore, the serum levels of S100–A11 (P > 0.04) and AIF-1 (P > 0.01) were significantly higher in lymph node-positive patients as compared to lymph node-negative patients. The levels of TFF3 and DKK1 were higher (P < 0.0001) in controls than in cervical cancer patients and were not different in groups with or without nodal involvement.

Conclusion: S100–A11 and AIF-1 represent potential biomarkers in patients with cervical cancer. Moreover, the levels of S100–A11 and AIF-1 increase in patients with lymph node involvement.

Keywords:

oncogynecology – biomarkers – cervical cancer – S100–A11 – TFF-3 – AIF-1 – DKK1

Sources

1. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (6): 394–424. doi: 10.3322/caac.21492.

2. Cibula D, Petruželka L et al. Onkogynekologie. Praha: Grada Publishing a. s. 2009: 616.

3. ÚZIS ČR. [online]. Dostupné na: https: //www.uzis.cz/.

4. Tchagang AB, Tewfik AH, DeRycke MS et al. Early detection of ovarian cancer using group biomarkers. Mol Cancer Ther 2008; 7 (1): 27–37. doi: 10.1158/1535-7163.MCT-07-0565.

5. Lekskul N, Charakorn C, Lertkhachonsuk AA et al. The level of squamous cell carcinoma antigen and lymph node metastasis in locally advanced cervical cancer. Asian Pac J Cancer Prev 2015; 16 (11): 4719–4722. doi: 10.7314/apjcp.2015.16.11.4719.

6. Li D, Xu XX, Yan DD et al. Clinical significance of serum squamous cell carcinoma antigen in patients with early cervical squamous cell carcinoma. Zhonghua Zhong Liu Za Zhi 2019; 41 (5): 357–362. doi: 10.3760/cma.j.issn.0253-3766.2019.05.007.

7. Laengsri V, Kerdpin U, Plabplueng C et al. Cervical cancer markers: epigenetics and microRNAs. Lab Med 2018; 49 (2): 97–111. doi: 10.1093/labmed/lmx080.

8. Ikeda S, Yoshimura K, Onda T et al. Combination of squamous cell carcinoma-antigen, carcinoembryonic antigen, and carbohydrate antigen 19-9 predicts positive pelvic lymph nodes and parametrial involvement in early stage squamous cell carcinoma of the uterine cervix. J Obstet Gynaecol Res 2012; 38 (10): 1260–1265. doi: 10.1111/j.1447-0756.2012.01862.x.

9. Gaarenstroom KN, Bonfrer JM, Kenter GG et al. Clinical value of pretreatment serum Cyfra 21-1, tissue polypeptide antigen, and squamous cell carcinoma antigen levels in patients with cervical cancer. Cancer 1995; 76 (5): 807–813. doi: 10.1002/1097-0142 (19950901) 76: 5<807:: aid-cncr2820760515>3.0.co; 2- m.

10. Thim L, Wöldike HF, Nielsen PF et al. Characterization of human and rat intestinal trefoil factor produced in yeast. Biochemistry 1995; 34 (14): 4757–4764. doi: 10.1021/bi00014a033.

11. Lau WH, Pandey V, Kong X et al. Trefoil factor-3 (TFF3) stimulates de novo angiogenesis in mammary carcinoma both directly and indirectly via IL-8/CXCR2. PLoS One 2015; 10 (11): e0141947. doi: 10.1371/journal.pone.0141947.

12. Neubert D, Ondrová D, Hambálek J et al. Elevated levels of TFF3 in endometrial cancer patients. Ceska Gynekol 2018; 83 (2): 109–114.

13. Meyerhardt JA, Mangu PB, Flynn PJ et al. Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol 2013; 31 (35): 4465–4470. doi: 10.1200/JCO.2013.50.7442.

14. Ducreux M, Cuhna AS, Caramella C et al. ESMO Guidelines Committee. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (Suppl 5): v56–v68. doi: 10.1093/annonc/mdv295.

15. Molina R, Marrades RM, Augé JM et al. Assessment of a combined panel of six serum tumor markers for lung cancer. Am J Respir Crit Care Med 2016; 193 (4): 427–437. doi: 10.1164/rccm.201404-0603OC.

16. Maděrka M, Pilka R, Neubert D et al. New serum tumor markers S100, TFF3 and AIF-1 and their possible use in oncogynecology. Ceska Gynekol 2019; 84 (4): 303–308.

17. Niehrs C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 2006; 25 (57): 7469–7481. doi: 10.1038/sj.onc.1210054.

18. Niida A, Hiroko T, Kasai M et al. DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway. Oncogene 2004; 23 (52): 8520–8526. doi: 10.1038/sj.onc.1207 892.

19. Glinka A, Wu W, Delius H et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 1998; 391 (6665): 357–362. doi: 10.1038/34848.

20. Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C et al. Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell 2001; 1 (3): 423–434. doi: 10.1016/s1534-5807 (01) 00041-7.

21. Schneider VA, Mercola M. Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes Dev 2001; 15 (3): 304–315. doi: 10.1101/gad.855601.

22. Polakis P. Wnt signaling and cancer. Genes Dev 2000; 14 (15): 1837–1851.

23. Kim BG. Squamous cell carcinoma antigen in cervical cancer and beyond. J Gynecol Oncol 2013; 24 (4): 291–292. doi: 10.3802/ jgo.2013.24.4.291.

24. He SM, Xing F, Sui H et al. Determination of CA-125 levels in the serum, cervical and vaginal secretions, and endometrium in Chinese women with precancerous disease or endometrial cancer. Med Sci Monit 2011; 17 (11): CR618–CR625. doi: 10.12659/msm.882046.

25. Kotowicz B, Fuksiewicz M, Kowalska M et al. The value of tumor marker and cytokine analysis for the assessment of regional lymph node status in cervical cancer patients. Int J Gynecol Cancer 2008; 18 (6): 1279–1284. doi: 10.1111/ j.1525-1438.2007.01176.x.