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Erschienen in: Tumor Biology 2/2016

11.09.2015 | Original Article

Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non-small cell lung cancer

verfasst von: Ting Wang, Yiqian Liang, Asmitananda Thakur, Shuo Zhang, Tian Yang, Tianjun Chen, Lei Gao, Mingwei Chen, Hui Ren

Erschienen in: Tumor Biology | Ausgabe 2/2016

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Abstract

Biochemical markers play a significant role in the diagnosis of lung cancer. Recent studies have demonstrated a link involving S100 Calcium Binding Proteins (S100A2, S100A6) and non-small cell lung cancer (NSCLC), but the expediency of their serum levels in NSCLC has not been established. In this study, we evaluate the potential of serum S100A2 and S100A6 levels as diagnostic markers for NSCLC. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of S100A2 and S100A6 in 141 NSCLC patients and 150 healthy subjects. Serum levels of the two proteins in patients with NSCLC were higher compared to healthy controls (P = 0.0002 for S100A2 and P < 0.0001 for S100A6). Moreover, the levels of S100A2 and S100A6 were higher in the sera of stage I/II NSCLC patients compared to healthy controls with P = 0.01 and <0.0001, respectively. Receiver operating characteristic (ROC) analysis showed that S100A2 could distinguish NSCLC patients from healthy controls (AUC = 0.646), and S100A6 could also identify NSCLC (AUC = 0.668). Meanwhile, these two proteins showed notable capabilities for distinguishing stage I/II NSCLC from healthy controls (AUC = 0.708 for S100A2 and AUC = 0.702 for S100A6). Our results indicate that serum levels of S100A2 and S100A6 are significantly elevated in early stage NSCLC and may have the potential for NSCLC biomarker. Further studies with large sample population would help validate our findings.
Literatur
1.
Zurück zum Zitat Yu H, Han Z, Wang Y, Xin H. The clonal evolution and therapeutic approaches of lung cancer. Cell Biochem Biophys. 2014;70:63–71.CrossRefPubMed Yu H, Han Z, Wang Y, Xin H. The clonal evolution and therapeutic approaches of lung cancer. Cell Biochem Biophys. 2014;70:63–71.CrossRefPubMed
3.
Zurück zum Zitat Travis WD, Rekhtman N. Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing. Semin Respir Crit Care Med. 2011;32:22–31.CrossRefPubMed Travis WD, Rekhtman N. Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing. Semin Respir Crit Care Med. 2011;32:22–31.CrossRefPubMed
4.
Zurück zum Zitat Nicholson AG, Gonzalez D, Shah P, Pynegar MJ, Deshmukh M, Rice A, et al. Refining the diagnosis and egfr status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, ttf-1, cytokeratin 5/6, and p63, and egfr mutation analysis. J Thorac Oncol. 2010;5:436–41.CrossRefPubMed Nicholson AG, Gonzalez D, Shah P, Pynegar MJ, Deshmukh M, Rice A, et al. Refining the diagnosis and egfr status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, ttf-1, cytokeratin 5/6, and p63, and egfr mutation analysis. J Thorac Oncol. 2010;5:436–41.CrossRefPubMed
5.
Zurück zum Zitat Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31:992–1001.CrossRefPubMed Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31:992–1001.CrossRefPubMed
6.
Zurück zum Zitat Claiborne PM, Fowler CS, Vaporciyan AA. Follow-up of patients with resected thoracic malignancies. Thorac Surg Clin. 2012;22:123–31.CrossRefPubMed Claiborne PM, Fowler CS, Vaporciyan AA. Follow-up of patients with resected thoracic malignancies. Thorac Surg Clin. 2012;22:123–31.CrossRefPubMed
7.
Zurück zum Zitat Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.CrossRefPubMed Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.CrossRefPubMed
8.
Zurück zum Zitat Li X, Lu J, Ren H, Chen T, Gao L, Di L, et al. Combining multiple serum biomarkers in tumor diagnosis: a clinical assessment. Mol Clin Oncol. 2013;1:153–60.PubMed Li X, Lu J, Ren H, Chen T, Gao L, Di L, et al. Combining multiple serum biomarkers in tumor diagnosis: a clinical assessment. Mol Clin Oncol. 2013;1:153–60.PubMed
9.
Zurück zum Zitat Smith RA, Cokkinides V, Brooks D, Saslow D, Shah M, Brawley OW. Cancer screening in the United States, 2011: a review of current american cancer society guidelines and issues in cancer screening. CA cancer J Clin. 2011;61:8–30.CrossRefPubMed Smith RA, Cokkinides V, Brooks D, Saslow D, Shah M, Brawley OW. Cancer screening in the United States, 2011: a review of current american cancer society guidelines and issues in cancer screening. CA cancer J Clin. 2011;61:8–30.CrossRefPubMed
10.
11.
Zurück zum Zitat Stradal TB, Troxler H, Heizmann CW, Gimona M. Mapping the zinc ligands of s100a2 by site-directed mutagenesis. J Biol Chem. 2000;275:13219–27.CrossRefPubMed Stradal TB, Troxler H, Heizmann CW, Gimona M. Mapping the zinc ligands of s100a2 by site-directed mutagenesis. J Biol Chem. 2000;275:13219–27.CrossRefPubMed
12.
Zurück zum Zitat Nacken W, Roth J, Sorg C, Kerkhoff C. S100a9/s100a8: Myeloid representatives of the s100 protein family as prominent players in innate immunity. Microsc Res Tech. 2003;60:569–80.CrossRefPubMed Nacken W, Roth J, Sorg C, Kerkhoff C. S100a9/s100a8: Myeloid representatives of the s100 protein family as prominent players in innate immunity. Microsc Res Tech. 2003;60:569–80.CrossRefPubMed
13.
Zurück zum Zitat Donato R. Intracellular and extracellular roles of s100 proteins. Microsc Res Tech. 2003;60:540–51.CrossRefPubMed Donato R. Intracellular and extracellular roles of s100 proteins. Microsc Res Tech. 2003;60:540–51.CrossRefPubMed
14.
Zurück zum Zitat Naz S, Bashir M, Ranganathan P, Bodapati P, Santosh V, Kondaiah P. Protumorigenic actions of s100a2 involve regulation of pi3/akt signaling and functional interaction with smad3. Carcinogenesis. 2014;35:14–23.CrossRefPubMed Naz S, Bashir M, Ranganathan P, Bodapati P, Santosh V, Kondaiah P. Protumorigenic actions of s100a2 involve regulation of pi3/akt signaling and functional interaction with smad3. Carcinogenesis. 2014;35:14–23.CrossRefPubMed
15.
Zurück zum Zitat Bartling B, Rehbein G, Schmitt WD, Hofmann HS, Silber 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.CrossRefPubMed Bartling B, Rehbein G, Schmitt WD, Hofmann HS, Silber 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.CrossRefPubMed
16.
Zurück zum Zitat Emberley ED, Murphy LC, Watson PH. S100 proteins and their influence on pro-survival pathways in cancer. Biochem Cell Biol. 2004;82:508–15.CrossRefPubMed Emberley ED, Murphy LC, Watson PH. S100 proteins and their influence on pro-survival pathways in cancer. Biochem Cell Biol. 2004;82:508–15.CrossRefPubMed
17.
Zurück zum Zitat Mishra SK, Siddique HR, Saleem M. S100a4 calcium-binding protein is key player in tumor progression and metastasis: Preclinical and clinical evidence. Cancer Metastasis Rev. 2012;31:163–72.CrossRefPubMed Mishra SK, Siddique HR, Saleem M. S100a4 calcium-binding protein is key player in tumor progression and metastasis: Preclinical and clinical evidence. Cancer Metastasis Rev. 2012;31:163–72.CrossRefPubMed
18.
Zurück zum Zitat Salama I, Malone PS, Mihaimeed F, Jones JL. A review of the s100 proteins in cancer. Eur J Surg Oncol. 2008;34:357–64.CrossRefPubMed Salama I, Malone PS, Mihaimeed F, Jones JL. A review of the s100 proteins in cancer. Eur J Surg Oncol. 2008;34:357–64.CrossRefPubMed
19.
Zurück zum Zitat Wicki R, Franz C, Scholl FA, Heizmann CW, Schafer BW. Repression of the candidate tumor suppressor gene s100a2 in breast cancer is mediated by site specific hypermethylation. Cell Calcium. 1997;22:243–54.CrossRefPubMed Wicki R, Franz C, Scholl FA, Heizmann CW, Schafer BW. Repression of the candidate tumor suppressor gene s100a2 in breast cancer is mediated by site specific hypermethylation. Cell Calcium. 1997;22:243–54.CrossRefPubMed
20.
Zurück zum Zitat Wolf S, Haase-Kohn C, Pietzsch J. S100a2 in cancerogenesis: a friend or a foe? Amino Acids. 2011;41:849–61.CrossRefPubMed Wolf S, Haase-Kohn C, Pietzsch J. S100a2 in cancerogenesis: a friend or a foe? Amino Acids. 2011;41:849–61.CrossRefPubMed
21.
Zurück zum Zitat 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;15:22–9.CrossRefPubMed 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;15:22–9.CrossRefPubMed
22.
Zurück zum Zitat 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 in early-stage non-small cell lung cancer. Cancer Res. 2004;64:5564–9.CrossRefPubMed 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 in early-stage non-small cell lung cancer. Cancer Res. 2004;64:5564–9.CrossRefPubMed
23.
Zurück zum Zitat Ishii A, Suzuki M, Satomi K, Kobayashi H, Sakashita S, Kano J, et al. Increased cytoplasmic s100a6 expression is associated with pulmonary adenocarcinoma progression. Pathol Int. 2009;59:623–30.CrossRefPubMed Ishii A, Suzuki M, Satomi K, Kobayashi H, Sakashita S, Kano J, et al. Increased cytoplasmic s100a6 expression is associated with pulmonary adenocarcinoma progression. Pathol Int. 2009;59:623–30.CrossRefPubMed
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
25.
Zurück zum Zitat Melle C, Ernst G, Schimmel B, Bleul A, von Eggeling F. Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the ca(2+)-binding proteins s100a6 and s100a11. PLoS One. 2008;3:e3767.CrossRefPubMedPubMedCentral Melle C, Ernst G, Schimmel B, Bleul A, von Eggeling F. Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the ca(2+)-binding proteins s100a6 and s100a11. PLoS One. 2008;3:e3767.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Mischke D, Korge BP, Marenholz I, Volz A, Ziegler A. Genes encoding structural proteins of epidermal cornification and s100 calcium-binding proteins form a gene complex (“epidermal differentiation complex”) on human chromosome 1q21. J Investig Dermatol. 1996;106:989–92.CrossRefPubMed Mischke D, Korge BP, Marenholz I, Volz A, Ziegler A. Genes encoding structural proteins of epidermal cornification and s100 calcium-binding proteins form a gene complex (“epidermal differentiation complex”) on human chromosome 1q21. J Investig Dermatol. 1996;106:989–92.CrossRefPubMed
27.
Zurück zum Zitat Luu HH, Zhou L, Haydon RC, Deyrup AT, Montag AG, Huo D, et al. Increased expression of s100a6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma. Cancer Lett. 2005;229:135–48.CrossRefPubMed Luu HH, Zhou L, Haydon RC, Deyrup AT, Montag AG, Huo D, et al. Increased expression of s100a6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma. Cancer Lett. 2005;229:135–48.CrossRefPubMed
28.
Zurück zum Zitat McKiernan E, McDermott EW, Evoy D, Crown J, Duffy MJ. The role of s100 genes in breast cancer progression. Tumor Biol. 2011;32:441–50.CrossRef McKiernan E, McDermott EW, Evoy D, Crown J, Duffy MJ. The role of s100 genes in breast cancer progression. Tumor Biol. 2011;32:441–50.CrossRef
29.
Zurück zum Zitat Nonaka D, Chiriboga L, Rubin BP. Differential expression of s100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J Cutan Pathol. 2008;35:1014–9.CrossRefPubMed Nonaka D, Chiriboga L, Rubin BP. Differential expression of s100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J Cutan Pathol. 2008;35:1014–9.CrossRefPubMed
30.
Zurück zum Zitat Ohuchida K, Mizumoto K, Ishikawa N, Fujii K, Konomi H, Nagai E, et al. The role of s100a6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clin Cancer Res. 2005;11:7785–93.CrossRefPubMed Ohuchida K, Mizumoto K, Ishikawa N, Fujii K, Konomi H, Nagai E, et al. The role of s100a6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clin Cancer Res. 2005;11:7785–93.CrossRefPubMed
31.
Zurück zum Zitat Slomnicki LP, Nawrot B, Legniak W. S100a6 binds p53 and affects its activity. Int J Biochem Cell Biol. 2009;41:784–90.CrossRefPubMed Slomnicki LP, Nawrot B, Legniak W. S100a6 binds p53 and affects its activity. Int J Biochem Cell Biol. 2009;41:784–90.CrossRefPubMed
Metadaten
Titel
Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non-small cell lung cancer
verfasst von
Ting Wang
Yiqian Liang
Asmitananda Thakur
Shuo Zhang
Tian Yang
Tianjun Chen
Lei Gao
Mingwei Chen
Hui Ren
Publikationsdatum
11.09.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4057-z

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