Abstract
Aim: This study aims to perform differential protein expression analysis of serum samples from Oral Squamous Cell Carcinoma (OSCC) patients and healthy controls in search of potential diagnostic and/or prognostic biomarker(s).
Objective: OSCC is usually diagnosed late, which results in poor survival and high mortality. Identification of non-invasive prognostic biomarkers is of utmost importance for early diagnosis and proper management of the disease; hence we used a proteomic approach to identify potential biomarkers from serum.
Methods: Serum samples (OSCC n=45 and control n=30) were depleted, and proteins were separated using 2-D gel electrophoresis followed by identification by mass spectrometric analysis. Gene expression analysis of identified proteins in malignant and normal tissue was also performed to complement proteomics studies.
Results: Among differentially expressed proteins, up-regulation of heat shock protein alpha (HSP90α) from the serum of oral cancer patients was observed. We also observed elevated levels of Haptoglobin (HP) along with downregulation of Type II keratin cytoskeletal 1(KRT1) and serum albumin (ALB) in oral cancer patients. Gene expression studies on identified proteins in malignant and normal tissue revealed a similar pattern with the exception of KRT1. We believe that elevated levels of serum HSP90 alpha might be used as a potential biomarker.
Conclusion: Our findings suggest a contribution of HSP90 alpha and other identified proteins in oral pathology as pro/anti-apoptotic modulators, thus considering their potential as predictive biomarkers.
Keywords: Serum biomarkers, OSCC, HSP90alpha, KRT1, haptoglobin, proteomics.
Graphical Abstract
[http://dx.doi.org/10.1038/nrc2982] [PMID: 21160525]
[http://dx.doi.org/10.1016/j.oraloncology.2014.02.015] [PMID: 24656975]
[http://dx.doi.org/10.4061/2011/431246] [PMID: 21660266]
[http://dx.doi.org/10.1002/j.0022-0337.2001.65.4.tb03403.x] [PMID: 11336118]
[http://dx.doi.org/10.1155/2014/394696] [PMID: 25097551]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1111/j.1600-0714.2009.00754.x] [PMID: 19434816]
[http://dx.doi.org/10.1016/j.ijom.2019.02.015] [PMID: 30878273]
[http://dx.doi.org/10.15252/msb.20156297] [PMID: 28951502]
[http://dx.doi.org/10.1093/carcin/21.3.517] [PMID: 10688872]
[http://dx.doi.org/10.3390/cancers9110155] [PMID: 29137182]
[http://dx.doi.org/10.1002/elps.200500510] [PMID: 16568407]
[http://dx.doi.org/10.1016/j.archoralbio.2015.11.017] [PMID: 26691574]
[http://dx.doi.org/10.1016/j.jcms.2017.01.033] [PMID: 28318929]
[http://dx.doi.org/10.1038/nmeth1007-785] [PMID: 17901867]
[http://dx.doi.org/10.4317/jced.52736] [PMID: 27034760]
[http://dx.doi.org/10.1038/nbt1235] [PMID: 16900146]
[http://dx.doi.org/10.1074/mcp.RA117.000147] [PMID: 28821604]
[http://dx.doi.org/10.19080/IJCSMB.2018.05.555652]
[http://dx.doi.org/10.1007/s11010-015-2395-1] [PMID: 25854900]
[http://dx.doi.org/10.1155/2015/490531] [PMID: 26509158]
[http://dx.doi.org/10.1016/j.ymeth.2004.08.020] [PMID: 15722225]
[http://dx.doi.org/10.1146/annurev.ge.22.120188.003215] [PMID: 2853609]
[http://dx.doi.org/10.1016/j.tips.2016.11.009] [PMID: 28012700]
[http://dx.doi.org/10.1152/ajpcell.00167.2010] [PMID: 21325639]
[http://dx.doi.org/10.1073/pnas.0908151106] [PMID: 19965370]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0174] [PMID: 25316816]
[http://dx.doi.org/10.1016/j.bjoms.2017.01.008] [PMID: 28209383]
[PMID: 19528462]
[http://dx.doi.org/10.1111/febs.12147] [PMID: 23356585]
[http://dx.doi.org/10.1038/cddis.2014.555] [PMID: 25590805]
[PMID: 15298155]
[PMID: 21687958]
[PMID: 23060558]
[http://dx.doi.org/10.1016/j.cca.2009.03.033] [PMID: 19306859]
[http://dx.doi.org/10.1016/j.jprot.2013.09.019] [PMID: 24120528]
[http://dx.doi.org/10.1016/j.cca.2010.03.028] [PMID: 20359475]
[http://dx.doi.org/10.1016/j.jfda.2018.12.008] [PMID: 30987719]
[http://dx.doi.org/10.1074/mcp.M700520-MCP200] [PMID: 18458027]
[http://dx.doi.org/10.1515/cclm-2012-0197] [PMID: 23093274]
[http://dx.doi.org/10.1080/19336918.2015.1035504] [PMID: 26211665]
[http://dx.doi.org/10.1016/j.mam.2011.12.002] [PMID: 22230555]
[http://dx.doi.org/10.3109/10520295.2013.793394] [PMID: 23738795]
[http://dx.doi.org/10.1186/1758-5996-3-11] [PMID: 21676260]
[http://dx.doi.org/10.1016/S1040-8428(97)00015-2] [PMID: 9298326]
[http://dx.doi.org/10.1182/blood-2002-07-2143] [PMID: 12480711]
[http://dx.doi.org/10.1074/jbc.M114.618702] [PMID: 25605727]
[http://dx.doi.org/10.1016/j.ceb.2014.12.008] [PMID: 25599598]
[http://dx.doi.org/10.1073/pnas.81.14.4280] [PMID: 6205393]
[PMID: 23482752]
[http://dx.doi.org/10.1002/hep.28493] [PMID: 26853542]
[http://dx.doi.org/10.1186/s12957-015-0656-9] [PMID: 26292957]
[http://dx.doi.org/10.1002/jcb.26554]