Serum concentration of S100P protein in patients with colorectal cancer

Czech version

Authors: Petra Morávková ¹; D. Kohoutová ¹; M. Drahošová ²; J. Bureš ¹
Authors‘ workplace: II. interní gastroenterologická klinika LF UK a FN Hradec Králové ¹; Ústav klinické imunologie a alergologie, LF UK a FN Hradec Králové ²
Published in: Gastroent Hepatol 2017; 71(4): 293-298
Category: Clinical and Experimental Gastroenterology: Original Article
doi: https://doi.org/10.14735/amgh2017293

Overview

Background:
Colorectal cancer (CRC) is the third most frequent cancer worldwide and in the Czech Republic. S100P protein plays a significant role in colorectal carcinogenesis and in tumour metastatic progression. The aim of this prospective study was to assess the association between serum concentration of S100P protein and CRC.

Methods:
The study included 79 subjects – 36 controls and 43 patients with CRC. The CRC group was divided into subgroups according to tumour side (13 patients with right-sided CRC (CRC-R group) and 30 patients with left-sided CRC (CRC-L group)); stage of the disease (9 patients in clinical stage I, 7 in stage II, 13 in stage III and 13 in stage IV); and tumour grading (5 patients with well-differentiated tumour (G1), 24 patients with moderately-differentiated tumour (G2) and 11 patients with poorly-differentiated tumour (G3)). Serum concentrations of S100P protein were measured in peripheral blood samples using ELISA.

Results:
Serum S100P was significantly higher in the CRC group (median: 1251; inter-quartile range (IQR): 731–1749 ng/L) than in the controls (median: 765; IQR: 545–1158 ng/L); p = 0.012. Compared to the control group, serum S100P was significantly higher in patients with left-sided tumours (median: 1426; IQR: 739–1925 ng/L; p = 0.005), in clinical stage IV (median: 1622; IQR: 778–2154 ng/L; p = 0.008) and in patients with moderately-differentiated tumours (median: 1318; IQR: 853–1879 ng/L; p = 0.005). No difference was observed in the CRC-R group when compared with the controls and CRC-L group; p > 0.05.

Conclusion:
The study confirms a relationship between serum concentration of S100P protein and CRC. Significantly higher serum levels were observed in patients in clinical stage IV and patients with left-sided carcinoma.

Key words:
S100P – biomarker – colorectal cancer

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
7. 6. 2017

Accepted:
31. 7. 2017

Sources

1. Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136 (5): E359–E386. doi: 10.1002/ijc.29210.

2. Gregor J, Malúšková D, Mužík J et al. Epidemiologie kolorektálního karcinomu v České republice. [online]. Dostupné z: www.kolorektum.cz/index.php?pg=pro-odborniky-epidemiologie-kolorektalniho-karcinomu-epidemiologie-kolorektalniho-karcinomu-v-cr.

3. Mužík J, Dušek L, Šnajdrová L. Epidemiologie kolorektálního karcinomu v krajích České republiky. [online]. Dostupné z: www.kolorektum.cz/index.php?pg=pro-odborniky-epidemiologie-kolorektalniho-karcinomu-epidemiologie-kolorektalniho-karcinomu-v-krajich-ceske-republiky.

4. SVOD. Epidemiologie zhoubných nádorů v České republice. [online]. Dostupné z: www.svod.cz.

5. Moore BW, McGregor D. Chromatographic and electrophoretic fractionation of soluble proteins of brain and liver. J Biol Chem 1965; 240: 1647–1653.

6. Moravkova P, Kohoutova D, Rejchrt S et al. Role of S100 Proteins in Colorectal Carcinogenesis. Gastroenterology Res Pract 2016; 2016: 2632703. doi: 10.1155/ 2016/2632703.

7. Becker T, Gerke V, Kube E et al. S100P, a novel Ca (2+) -binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. Eur J Biochem 1992; 207 (2): 541–547.

8. Emoto Y, Kobayashi R, Akatsuka H et al. Purification and characterization of a new member of the S-100 protein family from human placenta. Biochem Biophys Res Commun 1992; 182 (3): 1246–1253.

9. Jin G, Wang S, Hu X et al. Characterization of the tissue-specific expression of the s100P gene which encodes an EF-hand Ca2+-binding protein. Mol Biol Rep 2003; 30 (4): 243–248.

10. Parkkila S, Pan P, Ward A et al. The calcium-binding protein S100P in normal and malignant human tissues. BMC Clin Pathol 2008; 8: 2. doi: 10.1186/1472-6890-8-2.

11. Koltzscher M, Neumann C, König S et al. Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P. Mol Biol Cell 2003; 14 (6): 2372–2384.

12. Austermann J, Nazmi AR, Müller-Tidow C et al. Characterization of the Ca2+-regulated ezrin-S100P interaction and its role in tumor cell migration. J Biol Chem 2008; 283 (43): 29331–29340. doi: 10.1074/jbc.M806145200.

13. Arumugam T, Simeone DM, Schmidt AM et al. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem 2004; 279 (7): 5059–5065.

14. Penumutchu SR, Chou RH, Yu C. Structural insights into calcium-bound S100P and the V domain of the RAGE complex. PLoS One 2014; 9 (8): e103947. doi: 10.1371/journal.pone.0103947.

15. Mercado-Pimentel ME, Onyeagucha BC, Li Q et al. The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells. FEBS letters 2015; 589 (18): 2388–2393. doi: 10.1016/j.febslet. 2015.07.010.

16. Chandramouli A, Mercado-Pimentel ME, Hutchinson A et al. The induction of S100P expression by the Prosta-glandin E2 (PGE2) /EP4 receptor signal-ing pathway in colon cancer cells. Cancer Biol Ther 2010; 10 (10): 1056–1066. doi: 10.4161/cbt.10.10.13373.

17. Lin F, Zhang P, Zuo Z et al. Thioredoxin-1 Promotes Colorectal Cancer Invasion and Metastasis through Crosstalk with S100P. Cancer Lett 2017; 401: 1–10. doi: 10.1016/j.canlet.2017.04. 036.

18. Birkenkamp-Demtroder K, Olesen SH, Sørensen FB et al. Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut 2005; 54 (3): 374–384.

19. Fuentes MK, Nigavekar SS, Arumu-gam T et al. RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways. Dis Colon Rectum 2007; 50 (8): 1230–1240.

20. Li JN, Zhao L, Wu J et al. Differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer. J Dig Dis 2012; 13 (1): 24–32. doi: 10.1111/j.1751-2980.2011.00551.x.

21. Dong L, Wang F, Yin X et al. Overexpression of S100P promotes colorectal cancer metastasis and decreases chemosen-sitivity to 5-FU in vitro. Mol Cell Biochem 2014; 389 (1–2): 257–264. doi: 10.1007/ s11010-013-1947-5.

22. Weidle UH, Birzele F, Krüger A. Molecular targets and pathways involved in liver metastasis of colorectal cancer. Clin Exp Metastasis 2015; 32 (6): 623–635. doi: 10.1007/s10585-015-9732-3.

23. Shen ZY, Fang Y, Zhen L et al. Analysis of the predictive efficiency of S100P on adverse prognosis and the pathogenesis of S100P-mediated invasion and metastasis of colon adenocarcinoma. Cancer Genet 2016; 209 (4): 143–153. doi: 10.1016/j.cancergen.2016.02.002.

24. Royse KE, Chen L, Berger DH et al. Expression of pattern recognition receptor genes and mortality in patients with colorectal adenocarcinoma. Int J Mol Epidemiol Genet 2017; 8 (2): 8–18.

25. Wang Q, Zhang YN, Lin GL et al. S100P, a potential novel prognostic marker in colorectal cancer. Oncol Rep 2012; 28 (1): 303–310. doi: 10.3892/or.2012.1794.

26. Benson AB 3rd, Venook AP, Ceder-quist L et al. Colon Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. [online]. Available from: www.nccn.org/professionals/physician_gls/pdf/colon_blocks.pdf.

27. Diederichs S, Bulk E, Steffen B et al. S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 2004; 64 (16): 5564–5569.

28. Mousses S, Bubendorf L, Wagner U et al. Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays. Cancer Res 2002; 62 (5): 1256–1260.

29. Schor AP, Carvalho FM, Kemp C et al. S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast. Oncol Rep 2006; 15 (1): 3–6.

30. Wang G, Platt-Higgins A, Carroll J et al. Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients. Cancer Res 2006; 66 (2): 1199–1207.

31. Ji J, Zhao L, Wang X et al. Differential expression of S100 gene family in human esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2004; 130 (8): 480–486.

32. Liang J, Luo G, Ning X et al. Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. Biochem Cell Biol 2007; 85 (3): 375–383.

33. Logsdon CD, Simeone DM, Binkley C et al. Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 2003; 63 (10): 2649–2657.

34. Crnogorac-Jurcevic T, Missiaglia E, Blaveri E et al. Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J Pathol 2003; 201 (1): 63–74.