Oral Oncology 50 (2014) e53–e54
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Incorporation of salivary metabolomics in oral cancer diagnostics
The process of malignant transformation of a cell involves abundant complex reactions affecting the phenotype and genotype, making it possible for the cell to survive under extremely hostile conditions. The reactions occurring at various levels cause permanent or temporary damage to the cell and leave their specific ‘prints’, to which we refer to as biomarkers; these may be in the form of molecules expressed to a greater or lesser extent, or it may be other protein changes which in turn affect the behavior of the cell. Numerous fields such as proteomics, genomics, etc. have immerged in the yesteryears which have provided us with the gene profiling of a disease, or the various mutations occurring at the level of protein transcription [1]. A novel technique studying the chemical processes involving metabolites within the cell is termed as metabolomics. The investigation of metabolites provides us with quantitative data in order to elucidate their dynamics related to the disease state [2], and the end products of such cellular processes collectively within the biological cell, tissue or organ are termed as Metabolome. The study of these metabolites is possible by studying the different cells which are a snapshot of the cellular processes, thus reflecting the gene and protein expression [3]. Vascular channels and lymphatics form an integral part of the tumour, by means of which the detached malignant cells, and their related details, are carried to different parts of the body. These systemic biofluids are in close proximity to salivary glands, and hence carry information encoded into the acinar cells, thus being transferred to saliva [4]. The metabolomes may also be transferred throughout the body by membrane bound microvesicles called exosomes, and are secreted by various cell types in diseased and non-diseased states [2]. The field of metabolomics has been explored with an aim to identify the unique metabolome signature for various malignancies. Studies conducted are more in tandem with breast cancer and other systemic disorders, but basic studies for identification of biomarkers provide promising avenues for cancer diagnostics. Metabolomics have been studied by capillary electrophoresis time-of-flight mass spectrophotometry (CE-TOF-MS), and the results have suggested sufficient accuracy with a high cross validation for various metabolites in oral cancer [4]. The other reliable method to have been studied is the UPLC-QTOFMS method which has been demonstrated to identify biomarkers as lactic acid, valine, phenylalanine in oral cancer. And furthermore, these metabolic profiles can also be used in non-neoplastic conditions, such as Sjogren’s syndrome [5], suggesting that biomarkers may provide us with information pertaining to various conditions beyond malignancies. A MEDLINE search of the terms ‘‘Salivary Metabolomics’’ gave only 14 results, and specifically 9 results with the term http://dx.doi.org/10.1016/j.oraloncology.2014.07.013 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
‘‘metabolome’’ or ‘‘metabolomics’’. The other articles related were to saliva being used as a diagnostic tool, a field which is well known and established. The application of salivary biomarkers is unquestionably incomplete without the studies carried out for malignancies. The metabolite signatures of oral cancer and leukoplakia carried out by Wei et al. [6] suggest the difference in levels of valine, lactic acid and phenylalanine in oral leukoplakia and oral cancer as compared to its controls, thereby providing us with invaluable information about the metabolites expressed in oral malignancies. Other cancers such as the breast and pancreas have been studied, and provide definitive salivary metabolomic signatures, which can aid in their diagnosis, and more importantly, monitoring the treatment, and response to treatment as suggested by Sugimoto et al. [4]. The advantage of using saliva has been portrayed by Bertram et al. [7], wherein they comment that gender and body mass index do not have an effect on the salivary metabolic signature, thus making it an independent, as well as a stable marker. Liu and Duan [8] provide an excellent review on the utility of saliva in diagnosis, as well as the difficulties encountered with using this versatile fluid for accurate diagnosis and monitoring of various diseases. As suggested by Yakob et al. [9], the future of salivary diagnostics will rely heavily on the collaboration of all the ‘omics’, and with an increase in the point-of-care methods within the last decade as put forth by Shankar and Routray [10], diagnosis and monitoring of various disorders based on saliva will increase manifold. The discovery of every new method makes us realize that we are only seeing the tip of the iceberg and the most intriguing part is the hidden ice which is yet to be decoded, making us marvel at the wonders of nature and its adaptive mechanisms. This also helps us discover techniques which enhance the capability to diagnose diseases at the earliest possible stage, so as to help in development of appropriate treatment plans, and aid in complete remission of any condition. Conflict of interest None. References [1] Beger RD. A review of applications of metabolomics in cancer. Metabolites 2013;3:552–74. [2] Bonne NJ, Wong DT. Salivary biomarker development using genomic, proteomic and metabolomic approaches. Genome Med 2012;4:82–93. [3] Spielmann N, Wong DT. Saliva: diagnostics and therapeutic perspectives. Oral Dis 2011;17:345–54. [4] Sugimoto M, Wong DT, Hirayama A, Soga T, Tomita M. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 2010;6(1):78–95. [5] Mikkonen JJW, Herrala M, Soininen P, Lappalainen R, et al. Metabolic profiling of saliva in patients with primary sjogren’s syndrome. Metabolomics 2013;3(3):128.
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Letter to the Editor / Oral Oncology 50 (2014) e53–e54
[6] Wei J, Xie G, Zhou Z, Shi P, Qiu Y, Zheng X, et al. Salviary metabolite signatures of oral cancer and leukoplakia. Int J Cancer 2011;129(9):2207–17. [7] Bertram HC, Eggers N, Eller N. Potential for human saliva for nuclear magnetic resonance-based metabolomics and for health-related biomarker identification. Anal Chem 2009;81(21):9188–93. [8] Liu J, Duan Y. Saliva: a potential media for disease diagnostics and monitoring. Oral Oncol 2012;48(7):569–77. [9] Yakob M, Fuentes L, Wang MB, Abemayor E, Wong DT. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances. Curr Oral Health Rep 2014;1(2):133–41. [10] Shankar AA, Routray S. Trends in salivary diagnostics – a 5-year review of oral oncology (2007–2011). Oral Oncol 2012;48(6):e22–3.
Akhil A. Shankar 1 Sheeba Alex Department of Oral Pathology & Microbiology, Y.M.T. Dental College, Institutional Area, Sector-4, Kharghar, Navi Mumbai 410210, India E-mail address: [email protected] (A.A. Shankar) Samapika Routray Department of Oral Pathology & Microbiology, Institute of Dental Sciences, ‘SOA’ University, Bhubaneswar, Odisha 751003, India Tel.: +91 9937149690. E-mail addresses: [email protected] Available online 12 August 2014
1
Tel.: +91 8108019148.
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Incorporation of salivary metabolomics in oral cancer diagnostics
The process of malignant transformation of a cell involves abundant complex reactions affecting the phenotype and genotype, making it possible for the cell to survive under extremely hostile conditions. The reactions occurring at various levels cause permanent or temporary damage to the cell and leave their specific ‘prints’, to which we refer to as biomarkers; these may be in the form of molecules expressed to a greater or lesser extent, or it may be other protein changes which in turn affect the behavior of the cell. Numerous fields such as proteomics, genomics, etc. have immerged in the yesteryears which have provided us with the gene profiling of a disease, or the various mutations occurring at the level of protein transcription [1]. A novel technique studying the chemical processes involving metabolites within the cell is termed as metabolomics. The investigation of metabolites provides us with quantitative data in order to elucidate their dynamics related to the disease state [2], and the end products of such cellular processes collectively within the biological cell, tissue or organ are termed as Metabolome. The study of these metabolites is possible by studying the different cells which are a snapshot of the cellular processes, thus reflecting the gene and protein expression [3]. Vascular channels and lymphatics form an integral part of the tumour, by means of which the detached malignant cells, and their related details, are carried to different parts of the body. These systemic biofluids are in close proximity to salivary glands, and hence carry information encoded into the acinar cells, thus being transferred to saliva [4]. The metabolomes may also be transferred throughout the body by membrane bound microvesicles called exosomes, and are secreted by various cell types in diseased and non-diseased states [2]. The field of metabolomics has been explored with an aim to identify the unique metabolome signature for various malignancies. Studies conducted are more in tandem with breast cancer and other systemic disorders, but basic studies for identification of biomarkers provide promising avenues for cancer diagnostics. Metabolomics have been studied by capillary electrophoresis time-of-flight mass spectrophotometry (CE-TOF-MS), and the results have suggested sufficient accuracy with a high cross validation for various metabolites in oral cancer [4]. The other reliable method to have been studied is the UPLC-QTOFMS method which has been demonstrated to identify biomarkers as lactic acid, valine, phenylalanine in oral cancer. And furthermore, these metabolic profiles can also be used in non-neoplastic conditions, such as Sjogren’s syndrome [5], suggesting that biomarkers may provide us with information pertaining to various conditions beyond malignancies. A MEDLINE search of the terms ‘‘Salivary Metabolomics’’ gave only 14 results, and specifically 9 results with the term http://dx.doi.org/10.1016/j.oraloncology.2014.07.013 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
‘‘metabolome’’ or ‘‘metabolomics’’. The other articles related were to saliva being used as a diagnostic tool, a field which is well known and established. The application of salivary biomarkers is unquestionably incomplete without the studies carried out for malignancies. The metabolite signatures of oral cancer and leukoplakia carried out by Wei et al. [6] suggest the difference in levels of valine, lactic acid and phenylalanine in oral leukoplakia and oral cancer as compared to its controls, thereby providing us with invaluable information about the metabolites expressed in oral malignancies. Other cancers such as the breast and pancreas have been studied, and provide definitive salivary metabolomic signatures, which can aid in their diagnosis, and more importantly, monitoring the treatment, and response to treatment as suggested by Sugimoto et al. [4]. The advantage of using saliva has been portrayed by Bertram et al. [7], wherein they comment that gender and body mass index do not have an effect on the salivary metabolic signature, thus making it an independent, as well as a stable marker. Liu and Duan [8] provide an excellent review on the utility of saliva in diagnosis, as well as the difficulties encountered with using this versatile fluid for accurate diagnosis and monitoring of various diseases. As suggested by Yakob et al. [9], the future of salivary diagnostics will rely heavily on the collaboration of all the ‘omics’, and with an increase in the point-of-care methods within the last decade as put forth by Shankar and Routray [10], diagnosis and monitoring of various disorders based on saliva will increase manifold. The discovery of every new method makes us realize that we are only seeing the tip of the iceberg and the most intriguing part is the hidden ice which is yet to be decoded, making us marvel at the wonders of nature and its adaptive mechanisms. This also helps us discover techniques which enhance the capability to diagnose diseases at the earliest possible stage, so as to help in development of appropriate treatment plans, and aid in complete remission of any condition. Conflict of interest None. References [1] Beger RD. A review of applications of metabolomics in cancer. Metabolites 2013;3:552–74. [2] Bonne NJ, Wong DT. Salivary biomarker development using genomic, proteomic and metabolomic approaches. Genome Med 2012;4:82–93. [3] Spielmann N, Wong DT. Saliva: diagnostics and therapeutic perspectives. Oral Dis 2011;17:345–54. [4] Sugimoto M, Wong DT, Hirayama A, Soga T, Tomita M. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 2010;6(1):78–95. [5] Mikkonen JJW, Herrala M, Soininen P, Lappalainen R, et al. Metabolic profiling of saliva in patients with primary sjogren’s syndrome. Metabolomics 2013;3(3):128.
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Letter to the Editor / Oral Oncology 50 (2014) e53–e54
[6] Wei J, Xie G, Zhou Z, Shi P, Qiu Y, Zheng X, et al. Salviary metabolite signatures of oral cancer and leukoplakia. Int J Cancer 2011;129(9):2207–17. [7] Bertram HC, Eggers N, Eller N. Potential for human saliva for nuclear magnetic resonance-based metabolomics and for health-related biomarker identification. Anal Chem 2009;81(21):9188–93. [8] Liu J, Duan Y. Saliva: a potential media for disease diagnostics and monitoring. Oral Oncol 2012;48(7):569–77. [9] Yakob M, Fuentes L, Wang MB, Abemayor E, Wong DT. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances. Curr Oral Health Rep 2014;1(2):133–41. [10] Shankar AA, Routray S. Trends in salivary diagnostics – a 5-year review of oral oncology (2007–2011). Oral Oncol 2012;48(6):e22–3.
Akhil A. Shankar 1 Sheeba Alex Department of Oral Pathology & Microbiology, Y.M.T. Dental College, Institutional Area, Sector-4, Kharghar, Navi Mumbai 410210, India E-mail address: [email protected] (A.A. Shankar) Samapika Routray Department of Oral Pathology & Microbiology, Institute of Dental Sciences, ‘SOA’ University, Bhubaneswar, Odisha 751003, India Tel.: +91 9937149690. E-mail addresses: [email protected] Available online 12 August 2014
1
Tel.: +91 8108019148.
