Identification of CALM as the potential serum biomarker for predicting the recurrence of nasopharyngeal carcinoma using a mass spectrometry-based comparative proteomic approach

Meng,Huiling; Zhu,Xiaodong; Li,Ling; Liang,Zhongguo; Li,Xiaoyu; Pan,Xinbin; Zeng,Fanyan; Qu,Song

doi:10.3892/ijmm.2017.3094

Identification of CALM as the potential serum biomarker for predicting the recurrence of nasopharyngeal carcinoma using a mass spectrometry-based comparative proteomic approach

Authors:
- Huiling Meng
- Xiaodong Zhu
- Ling Li
- Zhongguo Liang
- Xiaoyu Li
- Xinbin Pan
- Fanyan Zeng
- Song Qu
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Affiliations: Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
Published online on: August 9, 2017 https://doi.org/10.3892/ijmm.2017.3094
Pages: 1152-1164
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To date, there are no serum biomarkers available for the prediction of recurrent nasopharyngeal carcinoma (rNPC). The diagnosis of rNPC mostly depends on imaging and biopsy of diseased tissue; however, both of these methods work mostly if the target tumor is at an advanced stage. Therefore, the identificaqtion of recurrent biomarkers is urgently required. In the present study, we used tandem mass tag (TMT) labeling and high performance liquid chromatography (HPLC) fractionation followed by liquid chromatography-tandem mass spectrometry (LC‑MS/MS) to identify differentially expressed proteins. Serum was collected from 40 patients with NPC [recurrence (n=20) and no recurrence (n=20)]. Compared to non‑recurrent NPC (nrNPC), we found 59 proteins to be significantly dysregulated in rNPC; most of these have been previously reported to play a role in carcinogenesis. The dysregulation of calmodulin (CALM) was confirmed in 74 new patients [recurrence (n=32) and no recurrence (n=42)] by ELISA. Moreover, we performed a preliminary pathway analysis which revealed that oxidative phosphorylation was altered in the patients with rNPC compared to those with nrNPC. Taken together, these data identify a potential diagnostic biomarker for rNPC and elucidate the potential molecular mechanisms that are dysregulated and contribute to the pathogenesis of rNPC.

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1	Chen ZT, Liang ZG and Zhu XD: A review: Proteomics in nasopharyngeal carcinoma. Int J Mol Sci. 16:15497–15530. 2015. View Article : Google Scholar : PubMed/NCBI
2	Wei YS, Zheng YH, Liang WB, Zhang JZ, Yang ZH, Lv ML, Jia J and Zhang L: Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic analysis. Cancer. 112:544–551. 2008. View Article : Google Scholar
3	Du C, Ying H, Zhou J, Hu C and Zhang Y: Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Int J Clin Oncol. 18:464–471. 2013. View Article : Google Scholar
4	Tao YL, Li Y, Gao J, Liu ZG, Tu ZW, Li G, Xu BQ, Niu DL, Jiang CB and Yi W: Identifying FGA peptides as nasopharyngeal carcinoma-associated biomarkers by magnetic beads. J Cell Biochem. 113:2268–2278. 2012. View Article : Google Scholar : PubMed/NCBI
5	Zhong Yu LJ: Diagnostic progress of recurrent nasopharyngeal carcinoma. Clinical Imaging Technology. 24:1633–1674. 2009.
6	Sahu A, Nandakumar N, Sawant S and Krishna CM: Recurrence prediction in oral cancers: A serum Raman spectroscopy study. Analyst. 140:2294–2301. 2015. View Article : Google Scholar : PubMed/NCBI
7	Nicholson BD, Shinkins B, Pathiraja I, Roberts NW, James TJ, Mallett S, Perera R, Primrose JN and Mant D: Blood CEA levels for detecting recurrent colorectal cancer. Cochrane Database Syst Rev. 12:CD0111342015.
8	Li GP, Wang H, Lai YK, Chen SC, Lin MC, Lu G, Zhang JF, He XG, Qian CN and Kung HF: Proteomic profiling between CNE-2 and its strongly metastatic subclone S-18 and functional characterization of HSP27 in metastasis of nasopharyngeal carcinoma. Proteomics. 11:2911–2920. 2011. View Article : Google Scholar : PubMed/NCBI
9	Xiao Z, Li G, Chen Y, Li M, Peng F, Li C, Li F, Yu Y, Ouyang Y, Xiao Z and Chen Z: Quantitative proteomic analysis of formalin-fixed and paraffin-embedded nasopharyngeal carcinoma using iTRAQ labeling, two-dimensional liquid chromatography, and tandem mass spectrometry. J Histochem Cytochem. 58:517–527. 2010. View Article : Google Scholar : PubMed/NCBI
10	Seriramalu R, Pang WW, Jayapalan JJ, Mohamed E, Abdul-Rahman PS, Bustam AZ, Khoo AS and Hashim OH: Application of champedak mannose-binding lectin in the glycoproteomic profiling of serum samples unmasks reduced expression of alpha-2 macroglobulin and complement factor B in patients with nasopharyngeal carcinoma. Electrophoresis. 31:2388–2395. 2010. View Article : Google Scholar : PubMed/NCBI
11	Tang CE, Tan T, Li C, Chen ZC, Ruan L, Wang HH, Su T, Zhang PF and Xiao ZQ: Identification of Galectin-1 as a novel biomarker in nasopharyngeal carcinoma by proteomic analysis. Oncol Rep. 24:495–500. 2010.PubMed/NCBI
12	Cho WC, Yip TT, Yip C, Yip V, Thulasiraman V, Ngan RK, Yip TT, Lau WH, Au JS and Law SC: Identification of serum amyloid A protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling. Clin Cancer Res. 10:43–52. 2004. View Article : Google Scholar : PubMed/NCBI
13	Yang X, Dai W, Kwong DL, Szeto CY, Wong EH, Ng WT, Lee AW, Ngan RK, Yau CC and Tung SY: Epigenetic markers for non-invasive early detection of nasopharyngeal carcinoma by methylation-sensitive high resolution melting. Int J Cancer. 136:127–135. 2015. View Article : Google Scholar
14	White NM, Masui O, Desouza LV, Krakovska O, Metias S, Romaschin AD, Honey RJ, Stewart R, Pace K, Lee J, et al: Quantitative proteomic analysis reveals potential diagnostic markers and pathways involved in pathogenesis of renal cell carcinoma. Oncotarget. 5:506–518. 2013. View Article : Google Scholar
15	Tian X, Sun D, Zhao S, Xiong H and Fang J: Screening of potential diagnostic markers and therapeutic targets against colorectal cancer. Onco Targets Ther. 8:1691–1699. 2015.PubMed/NCBI
16	Yan LR, Wang DX, Liu H, Zhang XX, Zhao H, Hua L, Xu P and Li YS: A pro-atherogenic HDL profile in coronary heart disease patients: an iTRAQ labelling-based proteomic approach. PloS One. 9:e983682014. View Article : Google Scholar : PubMed/NCBI
17	Sandberg A, Branca RM, Lehtiö J and Forshed J: Quantitative accuracy in mass spectrometry based proteomics of complex samples: The impact of labeling and precursor interference. J Proteomics. 96:133–144. 2014. View Article : Google Scholar
18	Janvilisri T: Omics-based identification of biomarkers for naso-pharyngeal carcinoma. Dis Markers. 2015:7621282015. View Article : Google Scholar
19	Luftig M: Heavy LIFting: Tumor promotion and radioresistance in NPC. J Clin Invest. 123:4999–5001. 2013. View Article : Google Scholar : PubMed/NCBI
20	Uenishi K, Criss WE and Kakiuchi S: Calcium-activatable phosphodiesterase and calcium-dependent modulator protein in transplantable hepatoma tissues. J Biochem. 87:601–607. 1980. View Article : Google Scholar : PubMed/NCBI
21	Wei JW, Morris HP and Hickie RA: Positive correlation between calmodulin content and hepatoma growth rates. Cancer Res. 42:2571–2574. 1982.PubMed/NCBI
22	Colomer J, Agell N, Engel P and Bachs O: Expression of calmodulin and calmodulin binding proteins in lymphoblastoid cells. J Cell Physiol. 159:542–550. 1994. View Article : Google Scholar : PubMed/NCBI
23	Colomer J, Agell N, Engel P, Alberola-Ila J and Bachs O: Calmodulin expression during proliferative activation of human T lymphocytes. Cell calclum. 14:609–618. 1993. View Article : Google Scholar
24	Berchtold MW and Villalobo A: The many faces of calmodulin in cell proliferation, programmed cell death, autophagy, and cancer. Biochim Biophys Acta. 1843:398–435. 2014. View Article : Google Scholar
25	Liu GX, Sheng HF and Wu S: A study on the levels of calmodulin and DNA in human lung cancer cells. Br J Cancer. 73:889–901. 1996. View Article : Google Scholar
26	Schuller HM, Correa E, Orloff M and Reznik GK: Successful chemotherapy of experimental neuroendocrine lung tumors in hamsters with an antagonist of Ca²⁺/calmodulin. Cancer Res. 50:1645–1649. 1990.PubMed/NCBI
27	Lönn U and Lönn S: Increased growth inhibition and DNA lesions in human colon adenocarcinoma cells treated with methotrexate or 5-fluorodeoxyuridine followed by calmodulin inhibitor. Cancer Res. 48:3319–3323. 1988.
28	Hait WN, Gesmonde J and Cheng E: Effects of KS-501, KS-502 and their enantiomers on calmodulin-sensitive enzyme activity and cellular proliferation. Biochem Pharmacol. 50:69–74. 1995. View Article : Google Scholar : PubMed/NCBI
29	Yuan K, Yong S, Xu F, Zhou T, McDonald JM and Chen Y: Calmodulin antagonists promote TRA-8 therapy of resistant pancreatic cancer. Oncotarget. 6:25308–25319. 2015. View Article : Google Scholar : PubMed/NCBI
30	Mukhopadhyay D and Akbarali HI: Depletion of [Ca²⁺]i inhibits hypoxia-induced vascular permeability factor (vascular endothelial growth factor) gene expression. Biochem Biophys Res Commun. 229:733–738. 1996. View Article : Google Scholar : PubMed/NCBI
31	Salnikow K, Kluz T, Costa M, Piquemal D, Demidenko ZN, Xie K and Blagosklonny MV: The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia. Mol Cell Biol. 22:1734–1741. 2002. View Article : Google Scholar : PubMed/NCBI
32	Jung HJ, Kim JH, Shim JS and Kwon HJ: A novel Ca²⁺/calmodulin antagonist HBC inhibits angiogenesis and downregulates hypoxia-inducible factor. J Biol Chem. 285:25867–25874. 2010. View Article : Google Scholar : PubMed/NCBI