唾液组学在口腔癌诊断中的应用
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摘要
人类对唾液的探索有悠久的历史,其无创、快捷、安全、廉价等优势得到了大量学者的青睐。最新提出的唾液组学包含了唾液基因组学、转录组学、蛋白质组学、代谢组学、微生物组学及微小RNA等,其中储存的人类及口腔微生物的生物信息为各种口腔疾病以及全身系统性疾病的研究提供了重要信息。唾液与口腔癌所特有的解剖生理关系使得唾液组学与口腔癌关系的研究成为热点。大量研究试图通过检测唾液中的口腔癌生物标志物对口腔癌进行无创诊断,目前已有许多口腔癌生物学标志物在唾液中被相继发现。本文就唾液组学及其在口腔癌诊断中的应用进行综述。
Saliva analysis has long been considered a potential alternative to blood serum and urine analyses. This body fluid is gaining popularity due to its ease of collection, safety in handling, low cost and high efficiency. Salivaomics includes six diagnostic alphabets: salivary genomics, transcriptomics, proteomics, metabolomics, microbiomics and micro RNA(mi RNA). Saliva contains extensive biological information, thereby playing important role in the early diagnosis of oral disorder and several systemic diseases. Direct contact between saliva and oral cancer lesions makes measurement of tumour markers in saliva an attractive alternative to serum testing. Salivaomics may offer a robust alternative for clinicians in making clinical decision in the future. This article provides an updated review on the progress of salivaomics in oral cancer diagnosis.
Saliva analysis has long been considered a potential alternative to blood serum and urine analyses. This body fluid is gaining popularity due to its ease of collection, safety in handling, low cost and high efficiency. Salivaomics includes six diagnostic alphabets: salivary genomics, transcriptomics, proteomics, metabolomics, microbiomics and micro RNA(mi RNA). Saliva contains extensive biological information, thereby playing important role in the early diagnosis of oral disorder and several systemic diseases. Direct contact between saliva and oral cancer lesions makes measurement of tumour markers in saliva an attractive alternative to serum testing. Salivaomics may offer a robust alternative for clinicians in making clinical decision in the future. This article provides an updated review on the progress of salivaomics in oral cancer diagnosis.
引文
[1] Wong DT. Salivaomics[J]. J Am Dent Assoc, 2012, 143(10 Suppl): 19S-24S.
[2] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[3] Cheng YS, Rees T, Wright J. A review of research on salivary biomarkers for oral cancer detection[J]. Clin Transl Med, 2014, 3(1): 3.
[4] Sultan ZK, Najeeb S, Khan RS, et al. Salivaomics: an emerging approach in dentistry[J]. J Pak Dent Assoc, 2016, 25(2): 42-43.
[5] Looi ML, Zakaria H, Osman J, et al. Quantity and quality assessment of DNA extracted from saliva and blood[J]. Clin Lab, 2012, 58(3/4): 307-312.
[6] Yeh CK, Christodoulides NJ, Floriano PN, et al. Current development of saliva/oral fluid-based diagnostics[J]. Tex Dent J, 2010, 127(7): 651-661.
[7] Bassim CW, Ambatipudi KS, Mays JW, et al. Quantitative salivary proteomic differences in oral chronic graft-versus-host disease[J]. J Clin Immunol, 2012, 32(6): 1390-1399.
[8] Chandra A, Agnihotri A, Gupta S. Oral squamous cell carcinoma & p53: an overview[M]. Germany: LAP LAMBERT Academic Publishing, 2013.
[9] Cova MAMN, Castagnola M, Messana I, et al. Salivary qmics[M]. Berlin: Springer, 2015: 63-82.
[10] Kim EM, Jung CH, Kim J, et al. The p53/p21 complex regulates cancer cell invasion and apoptosis by targeting Bcl-2 family proteins[J]. Cancer Res, 2017, 77(11): 3092-3100.
[11] Bhatia V, Goel MM, Makker A. DNA methylation: an epigenetic mechanism in oral squamous cell carcinoma[J]. South Asian J Exp Biol, 2014, 4(2): 33- 41.
[12] Don KR, Ramani P, Ramshankar V, et al. Promoter hypermethylation patterns of P16, DAPK and MGMT in oral squamous cell carcinoma: a systematic review and meta-analysis[J]. Indian J Dent Res, 2014, 25(6): 797-805.
[13] Guerrero-Preston R, Soudry E, Acero J, et al. NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva[J]. Cancer Prev Res (Phila), 2011, 4(7): 1061-1072.
[14] Righini CA, de Fraipont F, Timsit JF, et al. Tumorspecific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence[J]. Clin Cancer Res, 2007, 13(4): 1179-1185.
[15] Nagata S, Hamada T, Yamada N, et al. Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma[J]. Cancer, 2012, 118(17): 4298-4308.
[16] El-Naggar AK, Mao L, Staerkel G, et al. Genetic heterogeneity in saliva from patients with oral squamous carcinomas: implications in molecular diagnosis and screening[J]. J Mol Diagn, 2001, 3(4): 164-170.
[17] Li Y, St John MA, Zhou X, et al. Salivary transcriptome diagnostics for oral cancer detection[J]. Clin Cancer Res, 2004, 10(24): 8442-8450.
[18] Brinkmann O, Kastratovic DA, Dimitrijevic MV, et al. Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population[J]. Oral Oncol, 2011, 47(1): 51-55.
[19] Lisa Cheng YS, Jordan L, Gorugantula LM, et al. Salivary interleukin-6 and -8 in patients with oral cancer and patients with chronic oral inflammatory diseases[J]. J Periodontol, 2014, 85(7): 956-965.
[20] Zhang X, Jung IH, Hwang YS. EGF enhances lowinvasive cancer cell invasion by promoting IMP-3 expression[J]. Tumour Biol, 2016, 37(2): 2555-2563.
[21] Sugimoto M, Wong DT, Hirayama A, et al. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles[J]. Metabolomics, 2010, 6(1): 78-95.
[22] 及昕, 崔磊华, 张宁, 等. 口腔鳞状细胞癌患者唾液的代谢组学分析[J]. 中国老年学, 2016, 36(3): 560-562. Ji X, Cui LH, Zhang N, et al. The metabolism of the saliva of oral squamous cell carcinoma patients[J]. Chin J Gerontol, 2016, 36(3): 560-562.
[23] 张书平, 丁继芬, 李宁毅. 唾液SA、CEA测定在口腔鳞状细胞癌诊断中的意义[J]. 现代口腔医学杂志, 2003, 17(6): 510-511. Zhang SP, Ding JF, Li NY. Significance of CEA and SA in saliva of patients with squamous cell carcinoma in oral and maxillofacial region[J]. J Mod Stomatol, 2003, 17(6): 510-511.
[24] Vajaria BN, Patel KR, Begum R, et al. Evaluation of serum and salivary total sialic acid andα-l-fucosidase in patients with oral precancerous conditions and oral cancer[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2013, 115(6): 764-771.
[25] Whitmore SE, Lamont RJ. Oral bacteria and cancer [J]. PLoS Pathog, 2014, 10(3): e1003933.
[26] Mager DL, Haffajee AD, Devlin PM, et al. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects[J]. J Transl Med, 2005, 3: 27.
[27] Pushalkar S, Ji X, Li Y, et al. Comparison of oral microbiota in tumor and non-tumor tissues of patients with oral squamous cell carcinoma[J]. BMC Microbiol, 2012, 12: 144.
[28] Furquim CP, Soares GM, Ribeiro LL, et al. The salivary microbiome and oral cancer risk: a pilot study in Fanconi anemia[J]. J Dent Res, 2017, 96 (3): 292-299.
[29] Salazar C, Nagadia R, Pandit P, et al. A novel salivabased microRNA biomarker panel to detect head and neck cancers[J]. Cell Oncol (Dordr), 2014, 37(5): 331-338.
[30] Momen-Heravi F, Trachtenberg AJ, Kuo WP, et al. Genomewide study of salivary microRNAs for detection of oral cancer[J]. J Dent Res, 2014, 93(7 Suppl): 86S-93S.
[31] Tasoulas J, Patsouris E, Giaginis C, et al. Salivaomics for oral diseases biomarkers detection[J]. Expert Rev Mol Diagn, 2016, 16(3): 285-295.
[2] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[3] Cheng YS, Rees T, Wright J. A review of research on salivary biomarkers for oral cancer detection[J]. Clin Transl Med, 2014, 3(1): 3.
[4] Sultan ZK, Najeeb S, Khan RS, et al. Salivaomics: an emerging approach in dentistry[J]. J Pak Dent Assoc, 2016, 25(2): 42-43.
[5] Looi ML, Zakaria H, Osman J, et al. Quantity and quality assessment of DNA extracted from saliva and blood[J]. Clin Lab, 2012, 58(3/4): 307-312.
[6] Yeh CK, Christodoulides NJ, Floriano PN, et al. Current development of saliva/oral fluid-based diagnostics[J]. Tex Dent J, 2010, 127(7): 651-661.
[7] Bassim CW, Ambatipudi KS, Mays JW, et al. Quantitative salivary proteomic differences in oral chronic graft-versus-host disease[J]. J Clin Immunol, 2012, 32(6): 1390-1399.
[8] Chandra A, Agnihotri A, Gupta S. Oral squamous cell carcinoma & p53: an overview[M]. Germany: LAP LAMBERT Academic Publishing, 2013.
[9] Cova MAMN, Castagnola M, Messana I, et al. Salivary qmics[M]. Berlin: Springer, 2015: 63-82.
[10] Kim EM, Jung CH, Kim J, et al. The p53/p21 complex regulates cancer cell invasion and apoptosis by targeting Bcl-2 family proteins[J]. Cancer Res, 2017, 77(11): 3092-3100.
[11] Bhatia V, Goel MM, Makker A. DNA methylation: an epigenetic mechanism in oral squamous cell carcinoma[J]. South Asian J Exp Biol, 2014, 4(2): 33- 41.
[12] Don KR, Ramani P, Ramshankar V, et al. Promoter hypermethylation patterns of P16, DAPK and MGMT in oral squamous cell carcinoma: a systematic review and meta-analysis[J]. Indian J Dent Res, 2014, 25(6): 797-805.
[13] Guerrero-Preston R, Soudry E, Acero J, et al. NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva[J]. Cancer Prev Res (Phila), 2011, 4(7): 1061-1072.
[14] Righini CA, de Fraipont F, Timsit JF, et al. Tumorspecific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence[J]. Clin Cancer Res, 2007, 13(4): 1179-1185.
[15] Nagata S, Hamada T, Yamada N, et al. Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma[J]. Cancer, 2012, 118(17): 4298-4308.
[16] El-Naggar AK, Mao L, Staerkel G, et al. Genetic heterogeneity in saliva from patients with oral squamous carcinomas: implications in molecular diagnosis and screening[J]. J Mol Diagn, 2001, 3(4): 164-170.
[17] Li Y, St John MA, Zhou X, et al. Salivary transcriptome diagnostics for oral cancer detection[J]. Clin Cancer Res, 2004, 10(24): 8442-8450.
[18] Brinkmann O, Kastratovic DA, Dimitrijevic MV, et al. Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population[J]. Oral Oncol, 2011, 47(1): 51-55.
[19] Lisa Cheng YS, Jordan L, Gorugantula LM, et al. Salivary interleukin-6 and -8 in patients with oral cancer and patients with chronic oral inflammatory diseases[J]. J Periodontol, 2014, 85(7): 956-965.
[20] Zhang X, Jung IH, Hwang YS. EGF enhances lowinvasive cancer cell invasion by promoting IMP-3 expression[J]. Tumour Biol, 2016, 37(2): 2555-2563.
[21] Sugimoto M, Wong DT, Hirayama A, et al. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles[J]. Metabolomics, 2010, 6(1): 78-95.
[22] 及昕, 崔磊华, 张宁, 等. 口腔鳞状细胞癌患者唾液的代谢组学分析[J]. 中国老年学, 2016, 36(3): 560-562. Ji X, Cui LH, Zhang N, et al. The metabolism of the saliva of oral squamous cell carcinoma patients[J]. Chin J Gerontol, 2016, 36(3): 560-562.
[23] 张书平, 丁继芬, 李宁毅. 唾液SA、CEA测定在口腔鳞状细胞癌诊断中的意义[J]. 现代口腔医学杂志, 2003, 17(6): 510-511. Zhang SP, Ding JF, Li NY. Significance of CEA and SA in saliva of patients with squamous cell carcinoma in oral and maxillofacial region[J]. J Mod Stomatol, 2003, 17(6): 510-511.
[24] Vajaria BN, Patel KR, Begum R, et al. Evaluation of serum and salivary total sialic acid andα-l-fucosidase in patients with oral precancerous conditions and oral cancer[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2013, 115(6): 764-771.
[25] Whitmore SE, Lamont RJ. Oral bacteria and cancer [J]. PLoS Pathog, 2014, 10(3): e1003933.
[26] Mager DL, Haffajee AD, Devlin PM, et al. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects[J]. J Transl Med, 2005, 3: 27.
[27] Pushalkar S, Ji X, Li Y, et al. Comparison of oral microbiota in tumor and non-tumor tissues of patients with oral squamous cell carcinoma[J]. BMC Microbiol, 2012, 12: 144.
[28] Furquim CP, Soares GM, Ribeiro LL, et al. The salivary microbiome and oral cancer risk: a pilot study in Fanconi anemia[J]. J Dent Res, 2017, 96 (3): 292-299.
[29] Salazar C, Nagadia R, Pandit P, et al. A novel salivabased microRNA biomarker panel to detect head and neck cancers[J]. Cell Oncol (Dordr), 2014, 37(5): 331-338.
[30] Momen-Heravi F, Trachtenberg AJ, Kuo WP, et al. Genomewide study of salivary microRNAs for detection of oral cancer[J]. J Dent Res, 2014, 93(7 Suppl): 86S-93S.
[31] Tasoulas J, Patsouris E, Giaginis C, et al. Salivaomics for oral diseases biomarkers detection[J]. Expert Rev Mol Diagn, 2016, 16(3): 285-295.