Hematopoietic lineage cell‑specific protein 1 immunoreactivity indicates an increased risk of poor overall survival in patients with ovarian carcinoma

Liu,Wenting; Kajiyama,Hiroaki; Shibata,Kiyosumi; Koya,Yoshihiro; Senga,Takeshi; Kikkawa,Fumitaka

doi:10.3892/ol.2018.8493

Hematopoietic lineage cell‑specific protein 1 immunoreactivity indicates an increased risk of poor overall survival in patients with ovarian carcinoma

Authors:
- Wenting Liu
- Hiroaki Kajiyama
- Kiyosumi Shibata
- Yoshihiro Koya
- Takeshi Senga
- Fumitaka Kikkawa
View Affiliations

Affiliations: Bell Research Center for Reproductive Health and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 4668550, Japan, Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 4668550, Japan, Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 4668550, Japan
Published online on: April 13, 2018 https://doi.org/10.3892/ol.2018.8493
Pages: 9406-9412

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hematopoietic lineage cell‑specific protein 1 (HS1) is a 75‑kDa intracellular protein that is expressed primarily in hematopoietic cells. Several previous studies have demonstrated the association between HS1 expression and a poor prognosis in hematopoietic malignancies; however, in solid tumors, no studies not been reported. The present study examined the distribution and expression of HS1 in human epithelial ovarian carcinoma (EOC) to determine its clinical significance. Paraffin sections were obtained from EOC tissues and immunostained with HS1 antibody, and then the staining intensities were evaluated. Overall survival (OS) was determined using the Kaplan‑Meier estimator method, and multivariate analysis was performed using the Cox proportional hazards analysis. In total, 195 patients with EOC (median age, 56 years) were enrolled into the present study. HS1 immunoreactivity was categorized based on expression levels: Low (89/195; 45.6%) and high (106/195; 54.4%). Results demonstrated no association between expression level(s) and any clinicopathological parameter including age, International Federation of Gynecology and Obstetrics (FIGO) staging, type of chemotherapy or type of surgery received. The 5‑year OS rates of patients who demonstrated low (n=89) and high (n=106) HS1 expression were 90.4 and 66.7%, respectively. The OS times for patients with high HS1 expression were significantly shorter compared with those for patients exhibiting low HS1 expression (P=0.0065). Results obtained from the multivariate analysis demonstrated that the FIGO stage and the amount of HS1 expressed were significant independent prognostic markers for poorer OS (hazard ratio, 3.539; 95% confidence interval, 1.221‑12.811; P=0.0187). High HS1 expression levels may serve as a useful biomarker in patients with EOC who are likely to exhibit an unfavorable clinical outcome.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Kajiyama H, Shibata K, Mizuno M, Umezu T, Suzuki S, Yamamoto E, Fujiwara S, Kawai M, Nagasaka T and Kikkawa F: Long-term clinical outcome of patients with recurrent epithelial ovarian carcinoma: Is it the same for each histological type? Int J Gynecol Cancer. 22:394–399. 2012. View Article : Google Scholar : PubMed/NCBI
3	Kikkawa F, Nawa A, Ino K, Shibata K, Kajiyama H and Nomura S: Advances in treatment of epithelial ovarian cancer. Nagoya J Med Sci. 68:19–26. 2006.PubMed/NCBI
4	Yoshikawa N, Kajiyama H, Mizuno M, Shibata K, Kawai M, Nagasaka T and Kikkawa F: Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: Analysis in Japanese women. J Gynecol Oncol. 25:118–123. 2014. View Article : Google Scholar : PubMed/NCBI
5	Eisenkop SM, Friedman RL and Wang HJ: Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: A prospective study. Gynecol Oncol. 69:103–108. 1998. View Article : Google Scholar : PubMed/NCBI
6	Kitamura D, Kaneko H, Miyagoe Y, Ariyasu T and Watanabe T: Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage. Nucleic Acids Res. 17:9367–9379. 1989.PubMed/NCBI
7	Kitamura D, Kaneko H, Taniuchi I, Akagi K, Yamamura K and Watanabe T: Molecular cloning and characterization of mouse HS1. Biochem Biophys Res Commun. 208:1137–1146. 1995. View Article : Google Scholar : PubMed/NCBI
8	Scielzo C, Bertilaccio MT, Simonetti G, Dagklis A, Ten Hacken E, Fazi C, Muzio M, Caiolfa V, Kitamura D, Restuccia U, et al: HS1 has a central role in the trafficking and homing of leukemic B cells. Blood. 116:3537–3546. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yamamoto T, Yamanashi Y and Toyoshima K: Association of Src-family kinase Lyn with B-cell antigen receptor. Immunol Rev. 132:187–206. 1993. View Article : Google Scholar : PubMed/NCBI
10	Yamanashi Y, Okada M, Semba T, Yamori T, Umemori H, Tsunasawa S, Toyoshima K, Kitamura D, Watanabe T and Yamamoto T: Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling. Proc Natl Acad Sci USA. 90:3631–3635. 1993. View Article : Google Scholar : PubMed/NCBI
11	Dehring DA, Clarke F, Ricart BG, Huang Y, Gomez TS, Williamson EK, Hammer DA, Billadeau DD, Argon Y and Burkhardt JK: Hematopoietic lineage cell-specific protein 1 functions in concert with the Wiskott-Aldrich syndrome protein to promote podosome array organization and chemotaxis in dendritic cells. J Immunol. 186:4805–4818. 2011. View Article : Google Scholar : PubMed/NCBI
12	Butler B, Kastendieck DH and Cooper JA: Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells. Nat Immunol. 9:887–897. 2008. View Article : Google Scholar : PubMed/NCBI
13	Caligaris-Cappio F, Bergui L, Tesio L, Corbascio G, Tousco F and Marchisio PC: Cytoskeleton organization is aberrantly rearranged in the cells of B chronic lymphocytic leukemia and hairy cell leukemia. Blood. 67:233–239. 1986.PubMed/NCBI
14	Thomas SG, Calaminus SD, Auger JM, Watson SP and Machesky LM: Studies on the actin-binding protein HS1 in platelets. BMC Cell Biol. 8:462007. View Article : Google Scholar : PubMed/NCBI
15	Hussein K, von Neuhoff N, Büsche G, Buhr T, Kreipe H and Bock O: Opposite expression pattern of Src kinase Lyn in acute and chronic haematological malignancies. Ann Hematol. 88:1059–1067. 2009. View Article : Google Scholar : PubMed/NCBI
16	Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M and Caligaris-Cappio F: HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses. J Clin Invest. 115:1644–1650. 2005. View Article : Google Scholar : PubMed/NCBI
17	Hao JJ, Zhu J, Zhou K, Smith N and Zhan X: The coiled-coil domain is required for HS1 to bind to F-actin and activate Arp2/3 complex. J Biol Chem. 280:37988–37994. 2005. View Article : Google Scholar : PubMed/NCBI
18	He H: HS1 and EMS1. Gan To Kagaku Ryoho. 24:1448–1453. 1997.(In Japanese). PubMed/NCBI
19	van Rossum AG, Schuuring-Scholtes E, van Buuren-van Seggelen V, Kluin PM and Schuuring E: Comparative genome analysis of cortactin and HS1: The significance of the F-actin binding repeat domain. BMC Genomics. 6:152005. View Article : Google Scholar : PubMed/NCBI
20	Schuuring E, van Damme H, Schuuring-Scholtes E, Verhoeven E, Michalides R, Geelen E, de Boer C, Brok H, van Buuren V and Kluin P: Characterization of the EMS1 gene and its product, human Cortactin. Cell Adhes Commun. 6:185–209. 1998. View Article : Google Scholar : PubMed/NCBI
21	Zhao G, Huang ZM, Kong YL, Wen DQ, Li Y, Ren L and Zhang HY: Cortactin is a sensitive biomarker relative to the poor prognosis of human hepatocellular carcinoma. World J Surg Oncol. 11:742013. View Article : Google Scholar : PubMed/NCBI
22	Ambrosio EP, Rosa FE, Domingues MA, Villacis RA, Coudry Rde A, Tagliarini JV, Soares FA, Kowalski LP and Rogatto SR: Cortactin is associated with perineural invasion in the deep invasive front area of laryngeal carcinomas. Hum Pathol. 42:1221–1229. 2011. View Article : Google Scholar : PubMed/NCBI
23	Lin CK, Chao TK, Yu CP, Yu MH and Jin JS: The expression of six biomarkers in the four most common ovarian cancers: Correlation with clinicopathological parameters. APMIS. 117:162–175. 2009. View Article : Google Scholar : PubMed/NCBI
24	Ni QF, Yu JW, Qian F, Sun NZ, Xiao JJ and Zhu JW: Cortactin promotes colon cancer progression by regulating ERK pathway. Int J Oncol. 47:1034–1042. 2015. View Article : Google Scholar : PubMed/NCBI
25	Noh SJ, Baek HA, Park HS, Jang KY, Moon WS, Kang MJ, Lee DG, Kim MH, Lee JH and Chung MJ: Expression of SIRT1 and cortactin is associated with progression of non-small cell lung cancer. Pathol Res Pract. 209:365–370. 2013. View Article : Google Scholar : PubMed/NCBI
26	Tavassoli FA and Devilee Peter: Pathology and genetics of tumours of the breast and female genital organs. Lyon: IAPS Press, 2003; 2003
27	Heintz AP, Odicino F, Maisonneuve P, Beller U, Benedet JL, Creasman WT, Ngan HY, Sideri M and Pecorelli S: Carcinoma of the ovary. J Epidemiol Biostat. 6:107–138. 2001.PubMed/NCBI
28	Miglarese MR, Mannion-Henderson J, Wu H, Parsons JT and Bender TP: The protein tyrosine kinase substrate cortactin is differentially expressed in murine B lymphoid tumors. Oncogene. 9:1989–1997. 1994.PubMed/NCBI
29	Zhan X, Haudenschild CC, Ni Y, Smith E and Huang C: Upregulation of cortactin expression during the maturation of megakaryocytes. Blood. 89:457–464. 1997.PubMed/NCBI
30	Mizutani K, Miki H, He H, Maruta H and Takenawa T: Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts. Cancer Res. 62:669–674. 2002.PubMed/NCBI
31	Schuuring E, Verhoeven E, Litvinov S and Michalides RJ: The product of the EMS1 gene, amplified and overexpressed in human carcinomas, is homologous to a v-src substrate and is located in cell-substratum contact sites. Mol Cell Biol. 13:2891–2898. 1993. View Article : Google Scholar : PubMed/NCBI
32	Gattazzo C, Martini V, Frezzato F, Trimarco V, Tibaldi E, Castelli M, Facco M, Zonta F, Brunati AM, Zambello R, et al: Cortactin, another player in the Lyn signaling pathway, is over-expressed and alternatively spliced in leukemic cells from patients with B-cell chronic lymphocytic leukemia. Haematologica. 99:1069–1077. 2014. View Article : Google Scholar : PubMed/NCBI
33	Xu XZ, Garcia MV, Li TY, Khor LY, Gajapathy RS, Spittle C, Weed S, Lessin SR and Wu H: Cytoskeleton alterations in melanoma: Aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression. Mod Pathol. 23:187–196. 2010. View Article : Google Scholar : PubMed/NCBI
34	Soslow RA: Histologic subtypes of ovarian carcinoma: An overview. Int J Gynecol Pathol. 27:161–174. 2008.PubMed/NCBI
35	Taniuchi I, Kitamura D, Maekawa Y, Fukuda T, Kishi H and Watanabe T: Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptor-coupled tyrosine kinases. EMBO J. 14:3664–3678. 1995.PubMed/NCBI
36	Park SH, Song JY, Kim YK, Heo JH, Kang H, Kim G, An HJ and Kim TH: Fascin1 expression in high-grade serous ovarian carcinoma is a prognostic marker and knockdown of fascin1 suppresses the proliferation of ovarian cancer cells. Int J Oncol. 44:637–646. 2014. View Article : Google Scholar : PubMed/NCBI
37	Hashimoto Y, Skacel M and Adams JC: Roles of fascin in human carcinoma motility and signaling: Prospects for a novel biomarker? Int J Biochem Cell Biol. 37:1787–1804. 2005. View Article : Google Scholar : PubMed/NCBI
38	Rottner K and Stradal TE: Actin dynamics and turnover in cell motility. Curr Opin Cell Biol. 23:569–578. 2011. View Article : Google Scholar : PubMed/NCBI