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Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach

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Pathology & Oncology Research

Abstract

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers and has been listed as sixth most common human cancer. Due to late diagnosis and insufficient therapeutic response among patients, the survival rate remains very low accentuating the importance of early diagnostic markers. The study aimed to identify differentially expressed proteins in search for putative serum biomarkers and drug targets. Serum samples (n = 45) were depleted and resolved on two dimensional gel electrophoresis. Among differentially expressed proteins, two were identified using MALDI-TOF mass spectrometry. Gene expression levels of identified proteins were quantified in malignant and normal tissue using RT-qPCR. To validate serum Rabl3 expression, sandwich ELISA was performed. Proteomics analysis revealed two proteins which were found to be associated with oral cancer. The expression of GIMAP7 was found to be down regulated in serum of patients suffering from oral cancer while the expression of Rabl3 was found to be up-regulated. Gene expression analysis in malignant tissue and adjacent normal tissue revealed the same pattern. Quantitative ELISA was used to validate expression of Rabl3 in serum from oral cancer patients and healthy subjects which demonstrated significant up-regulation in cancer patients. Findings in current study demonstrate differential expression of novel putative biomarkers GIMAP7 and Rabl3 in oral cancer which suggests their potential role in oral cancer pathology and can be considered as predictive biomarkers.

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References

  1. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22. https://doi.org/10.1038/nrc2982

    Article  CAS  PubMed  Google Scholar 

  2. Arantes LMRB, de Carvalho AC, Melendez ME, Carvalho AL, Goloni-Bertollo EM (2014) Methylation as a biomarker for head and neck cancer. Oral Oncol 50(6):587–592. https://doi.org/10.1016/j.oraloncology.2014.02.015

    Article  CAS  PubMed  Google Scholar 

  3. Tanaka T, Tanaka M, Tanaka T (2011) Oral carcinogenesis and oral cancer chemoprevention: a review. Pathol Res Int 2011:431246–431246. https://doi.org/10.4061/2011/431246

    Article  Google Scholar 

  4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492

    Article  PubMed  Google Scholar 

  5. Ali NS, Khuwaja AK, Ali T, Hameed R (2009) Smokeless tobacco use among adult patients who visited family practice clinics in Karachi, Pakistan. J Oral Pathol Med 38(5):416–421

    Article  PubMed  Google Scholar 

  6. Johnson N (2001) Tobacco use and oral cancer: a global perspective. J Dent Educ 65(4):328–339

    Article  CAS  PubMed  Google Scholar 

  7. Khan Z, Tönnies J, Müller S (2014) Smokeless tobacco and oral cancer in South Asia: a systematic review with meta-analysis. J Cancer Epidemiol 2014:394696–394696. https://doi.org/10.1155/2014/3946960

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gigliotti J, Madathil S, Makhoul N (2019) Delays in oral cavity cancer. Int J Oral Maxillofac Surg. https://doi.org/10.1016/j.ijom.2019.02.015

  9. Barbosa EB, Vidotto A, Polachini GM, Henrique T, Marqui AB, Tajara EH (2012) Proteomics: methodologies and applications to the study of human diseases. Rev Assoc Med Bras 58(3):366–375

    PubMed  Google Scholar 

  10. Turhani D, Krapfenbauer K, Thurnher D, Langen H, Fountoulakis M (2006) Identification of differentially expressed, tumor-associated proteins in oral squamous cell carcinoma by proteomic analysis. Electrophoresis 27(7):1417–1423. https://doi.org/10.1002/elps.200500510

    Article  CAS  PubMed  Google Scholar 

  11. Malik UU, Zarina S, Pennington SR (2016) Oral squamous cell carcinoma: key clinical questions, biomarker discovery, and the role of proteomics. Arch Oral Biol 63:53–65. https://doi.org/10.1016/j.archoralbio.2015.11.017

    Article  CAS  PubMed  Google Scholar 

  12. Blatt S, Kruger M, Ziebart T, Sagheb K, Schiegnitz E, Goetze E, Al-Nawas B, Pabst AM (2017) Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: a review of the literature. J Craniomaxillofac Surg 45(5):722–730. https://doi.org/10.1016/j.jcms.2017.01.033

    Article  PubMed  Google Scholar 

  13. Beretta L (2007) Proteomics from the clinical perspective: many hopes and much debate. Nat Methods 4(10):785–786. https://doi.org/10.1038/nmeth1007-785

    Article  CAS  PubMed  Google Scholar 

  14. Fernández-Olavarría A, Mosquera-Pérez R, Díaz-Sánchez R-M, Serrera-Figallo M-A, Gutiérrez-Pérez J-L, Torres-Lagares D (2016) The role of serum biomarkers in the diagnosis and prognosis of oral cancer: a systematic review. J Clin Exp Dent 8(2):e184–e193. https://doi.org/10.4317/jced.52736

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ilyas A, Hashim Z, Zarina S (2015) Effects of 5'-azacytidine and alendronate on a hepatocellular carcinoma cell line: a proteomics perspective. Mol Cell Biochem 405(1-2):53–61. https://doi.org/10.1007/s11010-015-2395-1

    Article  CAS  PubMed  Google Scholar 

  16. Musharraf SG, Hashmi N, Choudhary MI, Rizvi N, Usman A, Atta ur R (2012) Comparison of plasma from healthy nonsmokers, smokers, and lung cancer patients: pattern-based differentiation profiling of low molecular weight proteins and peptides by magnetic bead technology with MALDI-TOF MS. Biomarkers 17(3):223–230. https://doi.org/10.3109/1354750x.2012.657245

    Article  CAS  PubMed  Google Scholar 

  17. Bhurgri Y (2005) Cancer of the oral cavity - trends in Karachi South (1995-2002). Asian Pac J Cancer Prev 6(1):22–26

    PubMed  Google Scholar 

  18. Chen Y, Azman SN, Kerishnan JP, Zain RB, Chen YN, Wong YL, Gopinath SC (2014) Identification of host-immune response protein candidates in the sera of human oral squamous cell carcinoma patients. PLoS One 9(10):e109012. https://doi.org/10.1371/journal.pone.0109012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nitta T, Nasreen M, Seike T, Goji A, Ohigashi I, Miyazaki T, Ohta T, Kanno M, Takahama Y (2006) IAN family critically regulates survival and development of T lymphocytes. PLoS Biol 4(4):e103. https://doi.org/10.1371/journal.pbio.0040103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Poirier GM, Anderson G, Huvar A, Wagaman PC, Shuttleworth J, Jenkinson E, Jackson MR, Peterson PA, Erlander MG (1999) Immune-associated nucleotide-1 (IAN-1) is a thymic selection marker and defines a novel gene family conserved in plants. J Immunol 163(9):4960–4969

    CAS  PubMed  Google Scholar 

  21. Pandarpurkar M, Wilson-Fritch L, Corvera S, Markholst H, Hornum L, Greiner DL, Mordes JP, Rossini AA, Bortell R (2003) Ian4 is required for mitochondrial integrity and T cell survival. Proc Natl Acad Sci U S A 100(18):10382–10387. https://doi.org/10.1073/pnas.1832170100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schnell S, Demolliere C, van den Berk P, Jacobs H (2006) Gimap4 accelerates T-cell death. Blood 108(2):591–599. https://doi.org/10.1182/blood-2005-11-4616

    Article  CAS  PubMed  Google Scholar 

  23. Shiao YM, Chang YH, Liu YM, Li JC, Su JS, Liu KJ, Liu YF, Lin MW, Tsai SF (2008) Dysregulation of GIMAP genes in non-small cell lung cancer. Lung Cancer 62(3):287–294. https://doi.org/10.1016/j.lungcan.2008.03.021

    Article  PubMed  Google Scholar 

  24. Huang Z, Zhang W, Gao C, Ji B, Chi X, Zheng W, Wang HL (2016) Dysregulation of GTPase IMAP family members in hepatocellular cancer. Mol Med Rep 14(5):4119–4123. https://doi.org/10.3892/mmr.2016.5764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Colicelli J (2004) Human RAS superfamily proteins and related GTPases. Sci STKE 2004(250):Re13. https://doi.org/10.1126/stke.2502004re13

    Article  PubMed  PubMed Central  Google Scholar 

  26. Agarwal R, Jurisica I, Mills GB, Cheng KW (2009) The emerging role of the RAB25 small GTPase in cancer. Traffic (Copenhagen, Denmark) 10(11):1561–1568. https://doi.org/10.1111/j.1600-0854.2009.00969.x

    Article  CAS  Google Scholar 

  27. Li Q, Wang L, Zeng L, Zhang Y, Li K, Jin P, Su B, Wang L (2010) Evaluation of the novel gene Rabl3 in the regulation of proliferation and motility in human cancer cells. Oncol Rep 24(2):433–440

    CAS  PubMed  Google Scholar 

  28. Zhang W, Sun J, Luo J (2016) High expression of Rab-like 3 (Rabl3) is associated with poor survival of patients with non-small cell lung cancer via repression of MAPK8/9/10-Mediated autophagy. Med Sci Monit 22:1582–1588. https://doi.org/10.12659/MSM.898632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pan Y, Liu Z, Feng Z, Hui D, Huang X, Tong D, Jin Y (2017) The overexpression of Rabl3 is associated with pathogenesis and clinicopathologic variables in hepatocellular carcinoma. Tumour Biol 39(4):1010428317696230. https://doi.org/10.1177/1010428317696230

    Article  CAS  PubMed  Google Scholar 

  30. An J, Liu Z, Liang Q, Pan Y, Li H, Wang R, Jin Y (2017) Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma. Hum Pathol 67:146–151. https://doi.org/10.1016/j.humpath.2017.07.008

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Authors would like to acknowledge contribution of both patients and volunteers for this study.

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Authors and Affiliations

  1. National Center for Proteomics, University of Karachi, 75270, Karachi, Pakistan

    Muhammad Usman, Amber Ilyas, Zehra Hashim & Shamshad Zarina

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  1. Muhammad Usman
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  2. Amber Ilyas
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  3. Zehra Hashim
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  4. Shamshad Zarina
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Correspondence to Shamshad Zarina.

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The study was approved from Institutional Ethical Committee (IEC), University of Karachi (#NCP-IRB-108). All procedures adapted were as per 1964 Helsinki guidelines.

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Usman, M., Ilyas, A., Hashim, Z. et al. Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach. Pathol. Oncol. Res. 26, 1817–1822 (2020). https://doi.org/10.1007/s12253-019-00775-1

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  • DOI: https://doi.org/10.1007/s12253-019-00775-1

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