Validity and Prognostic Significance of Sperm Protein 17 As a Tumor Biomarker for Epithelial Ovarian Cancer: a Retrospective Study

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2018 Oct 13

PMID 30309325

Citations 7

Authors

Laurie L Brunette

Paulette Y Mhawech-Fauceglia

Lingyun Ji

Joseph G Skeate

Heike E Brand

Kate Lawrenson

Saloni Walia

Maurizio Chiriva-Internati

Susan Groshen

Lynda D Roman

W Martin Kast

Diane M Da Silva

Affiliations

Soon will be listed here.

Abstract

Background: Prior small studies have shown increased expression of sperm protein 17 (Sp17) in epithelial ovarian cancer (EOC) tissue and suggest Sp17 as a potential biomarker for EOC. However, how Sp17 expression varies with histology, grade, and stage of EOC and its expression in other ovarian neoplasms has not been defined. It is unknown whether patients with EOC have elevated serum Sp17 levels or if Sp17 expression is associated with survival outcomes.

Methods: The study included 982 patients with benign, borderline, and malignant ovarian neoplasms and normal ovary. There were 878 patients with tissue only, 39 with serum only, and 65 with matching serum and tissue. Immunohistochemical (IHC) staining with anti-Sp17 antibody was performed on tissue specimens and the intensity scored as weak, moderate, or strong. A sandwich enzyme-linked immunosorbent assay (ELISA) was performed to measure Sp17 sera concentrations.

Results: Sp17 expression was most commonly seen in serous cystadenomas (83%) and serous borderline tumors (100%). Of the 773 EOC specimens, 223 (30%) expressed Sp17. Grade and histology were significantly associated with Sp17 expression among EOC specimens (p < 0.001) on both univariate and multivariable analysis, with grade 1 serous adenocarcinomas showing the highest expression (51%). Sp17 expression was limited in other benign and non-epithelial malignant neoplasms. Neither Sp17 tissue expression nor serum concentration correlated with survival outcomes. Serum concentrations were higher in patients with Sp17 tissue expression, and the highest concentrations were noted among patients with serous and clear cell adenocarcinomas.

Conclusions: Sp17 is highly expressed in benign, borderline, and low grade malignant serous ovarian neoplasms and can be quantified in serum. Sp17 expression may have diagnostic significance in this subset of patients.

Citing Articles

Can serum ferritin serve as a biomarker for the prognosis of gynecological malignant tumors? A retrospective cohort study.

Zhang W, Chen Q, Cheng Y, Wang M, Tong J, Tang R Cancer Biomark. 2023; 39(2):127-136.

PMID: 38160345 PMC: 11002721. DOI: 10.3233/CBM-230040.

Th17-inducing dendritic cell vaccines stimulate effective CD4 T cell-dependent antitumor immunity in ovarian cancer that overcomes resistance to immune checkpoint blockade.

Luo Y, Shreeder B, Jenkins J, Shi H, Lamichhane P, Zhou K J Immunother Cancer. 2023; 11(11).

PMID: 37918918 PMC: 10626769. DOI: 10.1136/jitc-2023-007661.

Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens.

Schossig P, Coskun E, Arsenic R, Horst D, Sehouli J, Bergmann E Int J Mol Sci. 2023; 24(3).

PMID: 36768616 PMC: 9916968. DOI: 10.3390/ijms24032292.

Nucleic acid vaccination strategies for ovarian cancer.

Saha C, Bojdo J, Dunne N, Duary R, Buckley N, McCarthy H Front Bioeng Biotechnol. 2022; 10:953887.

PMID: 36420446 PMC: 9677957. DOI: 10.3389/fbioe.2022.953887.

The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy.

Zhao J, Xu Z, Liu Y, Wang X, Liu X, Gao Y Am J Cancer Res. 2022; 12(2):681-694.

PMID: 35261795 PMC: 8899981.

References

Anglesio M, Arnold J, George J, Tinker A, Tothill R, Waddell N . Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors. Mol Cancer Res. 2008; 6(11):1678-90. PMC: 6953412. DOI: 10.1158/1541-7786.MCR-08-0193. View

Prat J . Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 2013; 124(1):1-5. DOI: 10.1016/j.ijgo.2013.10.001. View

Wen Y, Richardson R, Widgren E, ORand M . Characterization of Sp17: a ubiquitous three domain protein that binds heparin. Biochem J. 2001; 357(Pt 1):25-31. PMC: 1221924. DOI: 10.1042/0264-6021:3570025. View

Vermeij R, Daemen T, de Bock G, de Graeff P, Leffers N, Lambeck A . Potential target antigens for a universal vaccine in epithelial ovarian cancer. Clin Dev Immunol. 2010; 2010. PMC: 2946591. DOI: 10.1155/2010/891505. View

Li F, Han Y, Liu Q, Wu B, Huang W, Zeng S . Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells. BMC Cancer. 2009; 9:323. PMC: 2753635. DOI: 10.1186/1471-2407-9-323. View

Gilks C, Ionescu D, Kalloger S, Kobel M, Irving J, Clarke B . Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol. 2008; 39(8):1239-51. DOI: 10.1016/j.humpath.2008.01.003. View

Grizzi F, Chiriva-Internati M, Franceschini B, Bumm K, Colombo P, Ciccarelli M . Sperm protein 17 is expressed in human somatic ciliated epithelia. J Histochem Cytochem. 2004; 52(4):549-54. DOI: 10.1177/002215540405200414. View

Chiriva-Internati M, Wang Z, Salati E, Timmins P, Lim S . Tumor vaccine for ovarian carcinoma targeting sperm protein 17. Cancer. 2002; 94(9):2447-53. DOI: 10.1002/cncr.10506. View

Yuan K, Frolova N, Xie Y, Wang D, Cook L, Kwon Y . Primary cilia are decreased in breast cancer: analysis of a collection of human breast cancer cell lines and tissues. J Histochem Cytochem. 2010; 58(10):857-70. PMC: 2942739. DOI: 10.1369/jhc.2010.955856. View

10.

Kim J, Dabiri S, Seeley E . Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma. PLoS One. 2011; 6(11):e27410. PMC: 3214062. DOI: 10.1371/journal.pone.0027410. View

11.

Jacob F, Meier M, Caduff R, Goldstein D, Pochechueva T, Hacker N . No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecol Oncol. 2011; 121(3):487-91. DOI: 10.1016/j.ygyno.2011.02.022. View

12.

Bast Jr R, Klug T, St John E, Jenison E, Niloff J, Lazarus H . A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983; 309(15):883-7. DOI: 10.1056/NEJM198310133091503. View

13.

Chiriva-Internati M, Yu Y, Mirandola L, Jenkins M, Chapman C, Cannon M . Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer. PLoS One. 2010; 5(5):e10471. PMC: 2868870. DOI: 10.1371/journal.pone.0010471. View

14.

Straughn Jr J, Shaw D, Guerrero A, Bhoola S, Racelis A, Wang Z . Expression of sperm protein 17 (Sp17) in ovarian cancer. Int J Cancer. 2004; 108(6):805-11. DOI: 10.1002/ijc.11617. View

15.

du Bois A, Ewald-Riegler N, de Gregorio N, Reuss A, Mahner S, Fotopoulou C . Borderline tumours of the ovary: A cohort study of the Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study Group. Eur J Cancer. 2013; 49(8):1905-14. DOI: 10.1016/j.ejca.2013.01.035. View

16.

Juretic A, Spagnoli G, Schultz-Thater E, Sarcevic B . Cancer/testis tumour-associated antigens: immunohistochemical detection with monoclonal antibodies. Lancet Oncol. 2003; 4(2):104-9. DOI: 10.1016/s1470-2045(03)00982-3. View

17.

Radford R, Slattery C, Jennings P, Blacque O, Blaque O, Pfaller W . Carcinogens induce loss of the primary cilium in human renal proximal tubular epithelial cells independently of effects on the cell cycle. Am J Physiol Renal Physiol. 2012; 302(8):F905-16. PMC: 3729533. DOI: 10.1152/ajprenal.00427.2011. View

18.

Kurman R, Shih I . The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded. Am J Pathol. 2016; 186(4):733-47. PMC: 5808151. DOI: 10.1016/j.ajpath.2015.11.011. View

19.

Nakazato T, Kanuma T, Tamura T, Faried L, Aoki H, Minegishi T . Sperm protein 17 influences the tissue-specific malignancy of clear cell adenocarcinoma in human epithelial ovarian cancer. Int J Gynecol Cancer. 2007; 17(2):426-32. DOI: 10.1111/j.1525-1438.2007.00815.x. View

20.

Scanlan M, Gure A, Jungbluth A, Old L, Chen Y . Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002; 188:22-32. DOI: 10.1034/j.1600-065x.2002.18803.x. View