Abstract
S100 proteins have been implicated in the progression and metastasis of several cancers. Among the S100 family, S100A9 is reportedly expressed in non-small cell lung cancer (NSCLC), though the clinical significance and prognostic value of S100A9 expression in NSCLC remains unclear. The aim of the present study was to examine the relationship between S100A9 expression and prognosis in NSCLC patients. S100A9 expression was evaluated by immunohistochemical staining. Seventy patients with NSCLC who had undergone lung resection were enrolled in the study. Overexpression of S100A9 was observed in 38 (54.3%) patients. Kaplan–Meier analysis showed that, following surgery, patients overexpressing S100A9 had a significantly lower 5-year overall survival rate than patients with weak or no expression of S100A9 (P = 0.005). This finding was also observed in pathological stage IA patients (P = 0.03). Multivariate Cox regression analysis revealed overexpression of S100A9 to be an independent factor predictive of poor disease outcome (hazard ratio, 0.3; 95% confidence interval, 0.1–0.8; P = 0.02). Our results suggest that overexpression of S100A9 is associated with a poor prognosis among NSCLC patients and could serve as a marker identifying patients who are at high risk, even at an early pathological stage.
Similar content being viewed by others
References
Brundage MD, Dabies D, Mackillop MJ. Prognostic factors in non-small cell lung cancer: a decade of progress. Chest. 2002;122:1037–57.
Coate LE, John T, Tsao MS, Shepherd FA. Molecular predictive and prognostic markers in non-small cell lung cancer. Lancet Oncol. 2009;10:1001–10.
Cox G, Jones JL, Andi A, Waller DA, O’Byme KJ. A biological staging model for operable non-small cell lung cancer. Thorax. 2001;56:561–6.
Esposito V, Baldi A, Tonini G, Vincenzi B, Santini M, Ambrogi V, et al. Analysis of cell cycle regulator proteins in non-small cell lung cancer. J Clin Pathol. 2004;57:58–63.
Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech. 2003;60:540–51.
Heizmann CW, Fritz G, Schafer BW. S100 proteins: structure, functions and pathology. Front Biosci. 2002;7:d1356–68.
Marenholz I, Heizmann CW, Fritz G. S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun. 2004;322:1111–22.
Petersen S, Aninat-Meyer M, Schluns K, Gellert K, Dietel M, Petersen I. Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung. Brit J Cancer. 2000;82:65–73.
Knosel T, Petersen S, Schwabe H, Schluns K, Stein U, Schlag PM, et al. Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases. Virchows Arch. 2002;440:187–94.
Goeze A, Schluns K, Wolf G, Thasler Z, Petersen S, Petersen I. Chromosomal imbalances of primary and metastatic lung adenocarcinomas. J Pathol. 2002;196:8–16.
Jee KJ, Gong G, Ahn SH, Park JM, Knuutila S. Gain in 1q is a common abnormality in phyllodes tumours of the breast. Anal Cell Pathol. 2003;25:89–93.
Koon N, Zaika A, Moskaluk CA, Frierson HF, Knuutila S, Powell SM, et al. Clustering of molecular alterations in gastroesophageal carcinomas. Neoplasia. 2004;6:143–9.
Sy SM, Wong N, Lee TW, Tse G, Mok TS, Fan B, et al. Distinct patterns of genetic alterations in adenocarcinoma and squamous cell carcinoma of the lung. Eur J Cancer. 2004;40:1082–94.
Sy SM, Wong N, Lai PB, To KF, Johnson PJ. Regional overreprentations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma. Mod Pathol. 2005;18:686–92.
Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P. Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade-results of an explorative CGH meta-analysis. Brit J Cancer. 2005;92:935–41.
Salama I, Malone PS, Mihaimeed F, Jones JL. A review of the S100 proteins in cancer. EJSO. 2008;34:357–64.
Manitz MP, Horst B, Seeliger S, Strey A, Skryabin BV, Gunzer M, et al. Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Mol Cell Biol. 2003;23:1034–43.
Hobbs JA, May R, Tanousis K, McNeill E, Mathies M, Gebhardt C, et al. Myeloid cell function in MRP-14 (S100A9) null mice. Mol Cell Biol. 2003;23:2564–76.
Arai K, Teratani T, Nozawa R, Yamada T. Immunohistochemical investigation of S100A9 expression in pulmonary adenocarcinoma: S100A9 expression is associated with tumor differentiation. Oncol Rep. 2001;8:591–6.
Moon A, Yong HY, Song JI, Cukovic D, Salagrama S, Kaplan D, et al. Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res. 2008;6:1544–53.
Arai K, Takano S, Teratani T, Ito Y, Yamada T, Nozawa R. S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr Cancer Drug Tar. 2008;8:243–52.
Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999;17:1474–81.
Allred DC, Harvey JM, Berardo MD, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–68.
Allred DC, Clark GM, Elledge R, Fuqua SA, Brown RW, Chamness GC, et al. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst. 1993;85:200–6.
Kimura K, Endo Y, Yonemura Y, Heizmann CW, Schäfer BW, Watanabe Y, et al. Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer. Int J Oncol. 2000;16:1125–31.
Diederichs S, Bulk E, Steffen B, Ji P, Tickenbrock L, Lang K, et al. S100 family members and trypsinogens are predictors of distant metastasis and survival early-stage non-small cell lung cancer. Cancer Res. 2004;64:5564–9.
Wang H, Zhang Z, Li R, Ang KK, Zhang H, Caraway NP, et al. Overexpression of S100A2 protein as a prognostic marker for patients with stage I non small cell lung cancer. Int J Cancer. 2005;116:285–90.
Miyazaki N, Abe Y, Oida Y, Suemizu H, Nishi M, Yamazaki H, et al. Poor outcome of patients with pulmonary adenocarcinoma showing decreased E-cadherin combined with increased S100A4 expression. Int J Oncol. 2006;28:1369–74.
Zech VFE, Dlaska M, Tzankov A, Hilbe W. Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100A2 in non-small cell lung cancer. Cancer Detect Prev. 2006;30:395–402.
Bartling B, Rehbein G, Schmitt WD, Hofmann HS, Bilber RE, Simm A. S100A2-S100P expression profile and diagnosis of non-small cell lung carcinoma: impairment by advanced tumour stages and neoadjuvant chemotherapy. Eur J Cancer. 2007;43:1935–43.
De Petris L, Orre LM, Kanter L, Pernemalm M, Koyi H, Lewensohn R, et al. Tumor expression of S100A6 correlates with survival of patients with stage I non-small-cell lung cancer. Lung Cancer. 2009;63:410–7.
Bulk E, Sargin B, Krug U, Hascher A, Jun Y, Knop M, et al. S100A2 induces metastasis in non-small cell lung cancer. Clin Cancer Res. 2009;15:22–8.
El-Rifai W, Moskaluk CA, Abdrabbo MK, Harper J, Yoshida C, Riggins GJ, et al. Gastric cancers overexpress S100A calcium-binding proteins. Cancer Res. 2002;62:6823–6.
Hermani A, Hess J, De Servi B, Medunjanin S, Grobholz R, Trojan L, et al. Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res. 2005;11:5146–52.
Arai K, Yamada T, Nozawa R. Immunohistochemical investigation of migration inhibitory factor-related protein (MRP)-14 expression in hepatocellular carcinoma. Med Oncol. 2000;17:183–8.
Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, et al. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood. 2004;104:4260–8.
Hunter MJ, Chazin W. High level expression and dimmer characterization of the S100 EF-hand proteins, migration inhibitory factor-related proteins 8 and 14. J Biol Chem. 1998;273:12427–35.
Gebhardt C, Nemeth J, Angel P, Hess J. S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol. 2006;72:1622–31.
Hiratsuka S, Watanabe A, Aburatani H, Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 2006;8:1369–75.
Taccioli C, Wan SG, Liu CG, Alder H, Volinia S, Farber JL, et al. Zinc replenishment reverses overexpression of the proinflammatory mediator S100A8 and esophageal preneoplasia in the rat. Gastroenterology. 2009;136:953–66.
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kawai, H., Minamiya, Y. & Takahashi, N. Prognostic impact of S100A9 overexpression in non-small cell lung cancer. Tumor Biol. 32, 641–646 (2011). https://doi.org/10.1007/s13277-011-0163-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-011-0163-8