Relationship Between S100A4 Protein Expression and Pre-operative Serum CA19.9 Levels in Pancreatic Carcinoma and Its Prognostic Significance

Overview

Journal World J Surg Oncol

Publisher Biomed Central

Specialties General Surgery
Oncology

Date 2019 Sep 19

PMID 31526392

Citations 4

Authors

Fuxin Jia

Mengmeng Liu

Xiao Li

Fen Zhang

Shuqiang Yue

Jiangwei Liu

Affiliations

Soon will be listed here.

Abstract

Background: Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC.

Methods: We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan-Meier analysis together with a single variable or multivariate Cox analysis.

Results: A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ = 0.202, P = 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ = - 0.280, P = 0.001), TNM stage (ρ = - 0.389, P = 0.000), and lymph node metastasis (ρ = 0.254, P = 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P = 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P = 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P = 0.000).

Conclusions: The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.

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References

Kijima H, Kashiwagi H, Dowaki S, Ohtani Y, Tobita K, Matsubayasi H . Stromal sialyl Le(a) expression is correlated with vascular invasion of human gallbladder adenocarcinoma. Int J Oncol. 2000; 17(1):55-60. DOI: 10.3892/ijo.17.1.55. View

Rosty C, Ueki T, Argani P, Jansen M, Yeo C, Cameron J . Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Am J Pathol. 2002; 160(1):45-50. PMC: 1867115. DOI: 10.1016/S0002-9440(10)64347-7. View

Engelkamp D, Schafer B, Erne P, Heizmann C . S100 alpha, CAPL, and CACY: molecular cloning and expression analysis of three calcium-binding proteins from human heart. Biochemistry. 1992; 31(42):10258-64. DOI: 10.1021/bi00157a012. View

Oida Y, Yamazaki H, Tobita K, Mukai M, Ohtani Y, Miyazaki N . Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer. Oncol Rep. 2006; 16(3):457-63. View

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun M . Cancer statistics, 2007. CA Cancer J Clin. 2007; 57(1):43-66. DOI: 10.3322/canjclin.57.1.43. View

Watanabe Y, Kobayashi R, Ishikawa T, Hidaka H . Isolation and characterization of a calcium-binding protein derived from mRNA termed p9Ka, pEL-98, 18A2, or 42A by the newly synthesized vasorelaxant W-66 affinity chromatography. Arch Biochem Biophys. 1992; 292(2):563-9. DOI: 10.1016/0003-9861(92)90031-q. View

Salama I, Malone P, Mihaimeed F, Jones J . A review of the S100 proteins in cancer. Eur J Surg Oncol. 2007; 34(4):357-64. DOI: 10.1016/j.ejso.2007.04.009. View

Schneider M, Hansen J, Sheikh S . S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?. J Mol Med (Berl). 2008; 86(5):507-22. DOI: 10.1007/s00109-007-0301-3. View

Ai K, Lu L, Huang X, Chen W, Zhang H . Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer. World J Gastroenterol. 2008; 14(12):1931-5. PMC: 2700408. DOI: 10.3748/wjg.14.1931. View

10.

Schnelldorfer T, Ware A, Sarr M, Smyrk T, Zhang L, Qin R . Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible?. Ann Surg. 2008; 247(3):456-62. DOI: 10.1097/SLA.0b013e3181613142. View

11.

Boye K, Maelandsmo G . S100A4 and metastasis: a small actor playing many roles. Am J Pathol. 2009; 176(2):528-35. PMC: 2808059. DOI: 10.2353/ajpath.2010.090526. View

12.

Molina V, Visa L, Conill C, Navarro S, Escudero J, Auge J . CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer. Tumour Biol. 2011; 33(3):799-807. DOI: 10.1007/s13277-011-0297-8. View

13.

Sekine H, Chen N, Sato K, Saiki Y, Yoshino Y, Umetsu Y . S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells. Biochem Biophys Res Commun. 2012; 429(3-4):214-9. DOI: 10.1016/j.bbrc.2012.10.048. View

14.

Galli C, Basso D, Plebani M . CA 19-9: handle with care. Clin Chem Lab Med. 2013; 51(7):1369-83. DOI: 10.1515/cclm-2012-0744. View

15.

Mocci E, Milne R, Mendez-Villamil E, Hopper J, John E, Andrulis I . Risk of pancreatic cancer in breast cancer families from the breast cancer family registry. Cancer Epidemiol Biomarkers Prev. 2013; 22(5):803-11. PMC: 3739843. DOI: 10.1158/1055-9965.EPI-12-0195. View

16.

Tsukamoto N, Egawa S, Akada M, Abe K, Saiki Y, Kaneko N . The expression of S100A4 in human pancreatic cancer is associated with invasion. Pancreas. 2013; 42(6):1027-33. DOI: 10.1097/MPA.0b013e31828804e7. View

17.

Lee S, Kim H, Hwang J, Shin E, Lee H, Hwang D . CD24 and S100A4 expression in resectable pancreatic cancers with earlier disease recurrence and poor survival. Pancreas. 2014; 43(3):380-8. DOI: 10.1097/MPA.0000000000000097. View

18.

Tas F, Sen F, Keskin S, Kilic L, Yildiz I . Prognostic factors in metastatic pancreatic cancer: Older patients are associated with reduced overall survival. Mol Clin Oncol. 2014; 1(4):788-792. PMC: 3916173. DOI: 10.3892/mco.2013.131. View

19.

Boone B, Steve J, Zenati M, Hogg M, Singhi A, Bartlett D . Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014; 21(13):4351-8. DOI: 10.1245/s10434-014-3842-z. View

20.

Wang J, Raimondo M, Guha S, Chen J, Diao L, Dong X . Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer. J Cancer. 2014; 5(8):696-705. PMC: 4174514. DOI: 10.7150/jca.10094. View