Proteins S100A8 and S100A9 are potential biomarkers for renal cell carcinoma in the early stages: Results from a proteomic study integrated with bioinformatics analysis

Zhang,Limin; Jiang,Haowen; Xu,Gang; Wen,Hui; Gu,Bin; Liu,Jun; Mao,Shanghua; Na,Rong; Jing,Yan; Ding,Qiang; Zhang,Yuanfang

doi:10.3892/mmr.2015.3321

Proteins S100A8 and S100A9 are potential biomarkers for renal cell carcinoma in the early stages: Results from a proteomic study integrated with bioinformatics analysis

Authors:
- Limin Zhang
- Haowen Jiang
- Gang Xu
- Hui Wen
- Bin Gu
- Jun Liu
- Shanghua Mao
- Rong Na
- Yan Jing
- Qiang Ding
- Yuanfang Zhang
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Affiliations: Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: February 9, 2015 https://doi.org/10.3892/mmr.2015.3321
Pages: 4093-4100
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

In order to investigate the two members of the EF‑hand Ca2+ binding protein S100 family, S100A8 and S100A9, in renal cell carcinoma (RCC), serum samples were collected from patients with RCC, transitional cell carcinoma in the kidney, benign renal masses and normal controls. The samples were analyzed by isobaric tags for relative and absolute quantification technology to identify the differential expression of S100A8 and S100A9 in the respective groups. Hierarchical clustering analysis was then conducted for the samples and the relevant selected gene. The cross‑platform analysis for the external validation was performed by means of The Cancer Genome Atlas database, containing the gene/microRNA expression pattern and clinical information of patients with RCC. Immunohistochemical staining was used to verify the expression of S100A8 and S100A9 in the four groups. As a result, serum and mRNA expression levels of S100A8 and S100A9 were found to be upregulated in patients with RCC compared with the other three groups, which was consistent with the result of the upregulated expression of mRNA levels in RCC tissue. The overexpression of S100A8 and S100A9 in cancer cells was also confirmed by immunohistochemistry. In addition, bioinformatics revealed that let‑7, a microRNA formerly identified as an inhibiting factor of RCC was downregulated in RCC, which contrasted with S100A8. It was also complementary to the sequence at the 3' untranslated region terminal of S100A8. Therefore, indicating that S100A8 and S100A9 may serve as biomarkers for the detection of RCC.

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1	Weiss RH and Lin PY: Kidney cancer: identification of novel targets for therapy. Kidney Int. 69:224–232. 2006. View Article : Google Scholar : PubMed/NCBI
2	Vogelzang NJ, Priest ER and Borden L: Spontaneous regression of histologically proved pulmonary metastases from renal cell carcinoma: a case with 5-year followup. J Urol. 148:1247–1248. 1992.PubMed/NCBI
3	Schendel DJ, Oberneder R, Falk CS, et al: Cellular and molecular analyses of major histocompatibility complex (MHC) restricted and non-MHC-restricted effector cells recognizing renal cell carcinomas: Problems and perspectives for immunotherapy. J Mol Med (Berl). 75:400–413. 1997. View Article : Google Scholar
4	Donato R: S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 33:637–668. 2001. View Article : Google Scholar : PubMed/NCBI
5	Heizmann CW, Fritz G and Schäfer BW: S100 proteins: structure, functions and pathology. Front Biosci. 7:d1356–d1368. 2002. View Article : Google Scholar : PubMed/NCBI
6	Roth J, Vogl T, Sorg C, et al: Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 24:155–158. 2003. View Article : Google Scholar : PubMed/NCBI
7	Cheng P, Corzo CA, Luetteke N, et al: Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med. 205:2235–2249. 2008. View Article : Google Scholar : PubMed/NCBI
8	Gebhardt C, Németh J, Angel P, et al: S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol. 72:1622–1631. 2006. View Article : Google Scholar : PubMed/NCBI
9	Turovskaya O, Foell D, Sinha P, et al: RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis. 29:2035–2043. 2008. View Article : Google Scholar : PubMed/NCBI
10	Vogl T, Gharibyan AL and Morozova-Roche LA: Pro-Inflammatory S100A8 and S100A9 proteins: self-assembly into multifunctional mative and amyloid complexes. Int J Mol Sci. 13:2893–2917. 2012. View Article : Google Scholar
11	Marenholz I, Heizmann CW and Fritz G: S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun. 322:1111–1122. 2004. View Article : Google Scholar : PubMed/NCBI
12	Schäfer BW, Wicki R, Engelkamp D, et al: Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family. Genomics. 25:638–643. 1995. View Article : Google Scholar : PubMed/NCBI
13	Zimmer DB, Wright Sadosky P and Weber DJ: Molecular mechanisms of S100-target protein interactions. Microsc Res Tech. 60:552–559. 2003. View Article : Google Scholar : PubMed/NCBI
14	Mueller A, Schäfer BW, Ferrari S, et al: The calcium-binding protein S100A2 interacts with p53 and modulates its transcriptional activity. J Biol Chem. 280:29186–29193. 2005. View Article : Google Scholar : PubMed/NCBI
15	Kriajevska M, Tarabykina S, Bronstein I, et al: Metastasis-associated Mts1 (S100A4) protein modulates protein kinase C phosphorylation of the heavy chain of nonmuscle myosin. J Biol Chem. 273:9852–9856. 1998. View Article : Google Scholar : PubMed/NCBI
16	Salama I, Malone PS, Mihaimeed F, et al: A review of the S100 proteins in cancer. Eur J Surg Oncol. 34:357–364. 2008. View Article : Google Scholar
17	Emberley ED, Murphy LC and Watson PH: S100 proteins and their influence on pro-survival pathways in cancer. Biochem Cell Biol. 82:508–515. 2004. View Article : Google Scholar : PubMed/NCBI
18	Heizmann CW, Ackermann GE and Galichet A: Pathologies involving the S100 proteins and RAGE. Subcell Biochem. 45:93–138. 2007. View Article : Google Scholar
19	Hermani A, de Servi B, Medunjanin S, et al: S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells. Exp Cell Res. 312:184–197. 2006. View Article : Google Scholar
20	Hermani A, Hess J, de Servi B, et al: Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res. 11:5146–5152. 2005. View Article : Google Scholar : PubMed/NCBI
21	Ott HW, Lindner H, Sarg B, et al: Calgranulins in cystic fluid and serum from patients with ovarian carcinomas. Cancer Res. 63:7507–7514. 2003.PubMed/NCBI
22	Ghavami S, Rashedi I, Dattilo BM, et al: S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. J Leukoc Biol. 83:1484–1492. 2008. View Article : Google Scholar : PubMed/NCBI
23	Moon A, Yong HY, Song JI, et al: Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res. 6:1544–1553. 2008. View Article : Google Scholar : PubMed/NCBI
24	Ichikawa M, Williams R, Wang L, et al: S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res. 9:133–148. 2011. View Article : Google Scholar : PubMed/NCBI
25	Rafii S and Lyden D: S100 chemokines mediate bookmarking of premetastatic niches. Nat Cell Biol. 8:1321–1323. 2006. View Article : Google Scholar : PubMed/NCBI
26	Hiratsuka S, Watanabe A, Aburatani H, et al: Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 8:1369–1375. 2006. View Article : Google Scholar : PubMed/NCBI
27	Ozbek E, Aliskan T, Otunctemur A, et al: Comparison of tumor grade and stage with nuclear factor kappa b and p38 mitogene activated protein kinase expressions in renal cell cancer. Arch Ital Urol Androl. 84:53–60. 2012.PubMed/NCBI
28	Pal SK, Williams S, Josephson DY, et al: Novel therapies for metastatic renal cell carcinoma: efforts to expand beyond the VEGF/mTOR signaling paradigm. Mol Cancer Ther. 11:526–537. 2012. View Article : Google Scholar : PubMed/NCBI