Recent Progress in Mass Spectrometry-based Metabolomics for Colorectal Cancer

Abstract

Metabolomics, one of the latest omics technologies, is employed to reveal overall metabolic trajectories, identify disease causative mechanisms and provide information for preventive diagnosis and drug targeting. Cancer is a disease known to alter cellular metabolism and so metabolomics can play an important role in the early diagnosis of cancer and in the evaluation of medical interventions and treatments for cancer. Many metabolomics studies rely on high-sensitive and high-throughput mass spectrometry platforms. In recent years, various mass spectrometry(MS) methodologies have been developed and enriched the scope of metabolite detection, contributing to disease studies, such as diabetes, cancer, and depression. Colorectal cancer is the third most diagnosed cancer worldwide and its incidence ranked third in China. This review focuses on the mass spectrometry technologies in metabolomics and summarizes the progress of metabolomics research in colorectal cancer.

Keywords

Metabolomics / Mass spectrometry / Colorectal cancer / Biomarker

References

[1] Johnson C H, Ivanisevic J, Siuzdak G. Nat. Rev. Mol. Cell Biol., 201, 17: 451.

[2] Wishart D S. Nat. Rev. Drug Discov., 201, 15: 473.

[3] Troisi J, Tafuro M, Lombardi M, Scala G, Richards S M, Symes S J K, Ascierto P A, Delrio P, Tatangelo F, Buonerba C, Pierri B, Cerino P. Metabolites, 2022, 12: 110.

[4] Salmerón A M, Tristán A I, Abreu A C, Fernández I. Anal. Chem., 2022, 94: 417.

[5] Heiles S. Anal. Bioanal. Chem., 2021, 413: 5927.

[6] Markley J L, Brüschweiler R, Edison A S, Eghbalnia H R, Powers R, Raftery D, Wishart D S. Curr. Opin. Biotechnol., 2017, 43: 34.

[7] Luan H M, Wang X, Cai Z W. Mass Spec. Rev., 2019, 38: 22.

[8] Chi Q, Wang L, Xie D, Wang X. J. Pharm. Biomed. Anal., 2019, 168: 163.

[9] Liu Q, Chi Q, Fan R-T, Tian H-D, Wang X. Nat. Prod. Bioprospect., 2019, 9: 201.

[10] Xiao H-M, Wang X, Liao Q-L, Zhao S, Huang W-H, Feng Y-Q. Analyst, 2019, 144: 6578.

[11] Beccaria M, Cabooter D. Analyst, 2020, 145: 1129.

[12] Zhang A, Sun H, Wang P, Han Y, Wang X. Analyst, 2012, 137: 293.

[13] Seger C, Salzmann L. Clin. Biochem., 2020, 82: 2.

[14] Luginbühl M, Gaugler S. Clin. Biochem., 2020, 82: 33.

[15] Liu C, Qi K, Yao L, Xiong Y, Zhang X, Zang J, Tian C, Xu M, Yang J, Lin Z, Lv Y, Xiong W, Pan Y. Anal. Chem., 2019, 91: 6616.

[16] Zhu X, Xu T, Peng C, Wu S. Front. Chem., 2022, 9: 782432.

[17] Dueñas M E, Essner J J, Lee Y J. Sci. Rep., 2017, 7: 14946.

[18] Koppenol W H, Bounds P L, Dang C V. Nature Reviews Cancer, 2011, 11: 325.

[19] Stine Z E, Schug Z T, Salvino J M, Dang C V. Nat. Rev. Drug Discov., 2022, 21: 141.

[20] Yang M, Soga T, Pollard P J. J. Clin. Investig., 2013, 123: 3652.

[21] Zhang C, Zhou S, Chang H, Zhuang F, Shi Y, Chang L, Ai W, Du J, Liu W, Liu H, Zhou X, Wang Z, Hong T. Dis. Markers, 2021, 2021: 6858809.

[22] Martínez-Reyes I, Chandel N S. Nat. Rev. Cancer, 2021, 21: 669.

[23] Koeth R A, Wang Z, Levison B S, Buffa J A, Org E, Sheehy B T, Britt E B, Fu X, Wu Y, Li L, Smith J D, DiDonato J A, Chen J, Li H, Wu G D, Lewis J D, Warrier M, Brown J M, Krauss R M, Tang W H W, Bushman F D, Lusis A J, Hazen S L. Nat. Med., 2013, 19: 576.

[24] Yoo J Y, Sniffen S, McGill Percy K C, Pallaval V B, Chidipi B. Microorganisms, 2022, 10: 108.

[25] Liu X, Shao Y, Tu J, Sun J, Li L, Tao J, Chen J. Ann. Transl. Med., 2021, 9: 1670.

[26] Arneth B, Arneth R, Shams M. Int. J. Mol. Sci., 2019, 20: 2467.

[27] Izundegui D G, Nayor M. Curr. Diab. Rep., 2022, 22: 65.

[28] Karikari T K, Pascoal T A, Ashton N J, Janelidze S, Benedet A L, Rodriguez J L, Chamoun M, Savard M, Kang M S, Therriault J, Schöll M, Massarweh G, Soucy J-P, Höglund K, Brinkmalm G, Mattsson N, Palmqvist S, Gauthier S, Stomrud E, Zetterberg H, Hansson O, Rosa-Neto P, Blennow K. Lancet Neurol., 2020, 19: 422.

[29] Likhitweerawong N, Thonusin C, Boonchooduang N, Louthrenoo O, Nookaew I, Chattipakorn N, Chattipakorn S C. Metab. Brain Dis., 2021, 36: 1641.

[30] Peña-Bautista C, Baquero M, Vento M, Cháfer-Pericás C. Curr. Neuropharmacol., 2019, 17: 630.

[31] Li N, Lu B, Luo C, Cai J, Lu M, Zhang Y, Chen H, Dai M. Cancer Lett., 2021, 522: 255.

[32] Zheng R, Zeng H, Zhang S, Gu X, Sun K, Xia C, Yang Z, Li H, Chen W. J. Glob. Health, 2018, 2: 8.

[33] Sung H, Ferlay J, Siegel R L, Laversanne M, Soerjomataram I, Jemal A, Bray F. CA Cancer J. Clin., 2021, 71: 209.

[34] Chen H, Li N, Ren J, Feng X, Lyu Z, Wei L, Li X, Guo L, Zheng Z, Zou S, Zhang Y, Li J, Zhang K, Chen W, Dai M, He J. Gut, 2019, 68: 1450.

[35] Sawicki T, Ruszkowska M, Danielewicz A, Niedzwiedzka E, Arłukowicz T, Przybyłowicz K E. Cancers, 2021, 13: 2025.

[36] Shen J, Wu Y, Mo M, Feng X, Zhou C, Wang Z, Cai G, Zheng Y. Front. Oncol., 2021, 11: 702322.

[37] Akimoto N, Ugai T, Zhong R, Hamada T, Fujiyoshi K, Giannakis M, Wu K, Cao Y, Ng K, Ogino S. Nat. Rev. Clin. Oncol., 2021, 18: 230.

[38] Mangiapane L R, Nicotra A, Turdo A, Gaggianesi M, Bianca P, Di Franco S, Sardina D S, Veschi V, Signore M, Beyes S, Fagnocchi L, Fiori M E, Bongiorno M R, Lo Iacono M, Pillitteri I, Ganduscio G, Gulotta G, Medema J P, Zippo A, Todaro M, De Maria R, Stassi G. Gut, 2022, 71: 119.

[39] Caramujo-Balseiro S, Faro C, Carvalho L. Med. Hypotheses, 2021, 148: 110512.

[40] Biller L H, Schrag D. JAMA, 2021, 325: 669.

[41] Schmitt M, Greten F R. Nat. Rev. Immunol., 2021, 21: 653.

[42] Nenkov M, Ma Y, Gaßler N, Chen Y. Int. J. Mol. Sci., 2021, 22: 6262.

[43] Shen Y, Sun M, Zhu J, Wei M, Li H, Zhao P, Wang J, Li R, Tian L, Tao Y, Shen P, Zhang J. Molecular Omics, 2021, 17: 464.

[44] Shen X, Wang Y, Zhao R, Wan Q, Wu Y, Zhao L, Wu X. Int. J. Colorectal Dis., 2021, 36: 2215.

[45] Ecker J, Benedetti E, Kindt A S D, Höring M, Perl M, Machmüller A C, Sichler A, Plagge J, Wang Y, Zeissig S, Shevchenko A, Burkhardt R, Krumsiek J, Liebisch G, Janssen K-P. Gastroenterology, 2021, 161: 910.

[46] Kanth P, Inadomi J M. BMJ, 2021, 374: n1855.

[47] Alseekh S, Aharoni A, Brotman Y, Contrepois K, D’Auria J, Ewald J, C. Ewald J, Fraser P D, Giavalisco P, Hall R D, Heinemann M, Link H, Luo J, Neumann S, Nielsen J, Perez de Souza L, Saito K, Sauer U, Schroeder F C, Schuster S, Siuzdak G, Skirycz A, Sumner L W, Snyder M P, Tang H, Tohge T, Wang Y, Wen W, Wu S, Xu G, Zamboni N, Fernie A R. Nat. Methods, 2021, 18: 747.

[48] Cheng K, Brunius C, Fristedt R, Landberg R. Metabolomics, 2020, 16: 46.

[49] Rinschen M M, Ivanisevic J, Giera M, Siuzdak G. Nat. Rev. Mol. Cell Biol., 2019, 20: 353.

[50] Yang Q-J, Zhao J-R, Hao J, Li B, Huo Y, Han Y-L, Wan L-L, Li J, Huang J, Lu J, Yang G-J, Guo C. J. Cachexia Sarcopenia Muscle, 2018, 9: 71.

[51] Trifonova O P, Maslov D L, Balashova E E, Lokhov P G. Expert Rev. Proteomics, 2021, 18: 7.

[52] Adam M G, Beyer G, Christiansen N, Kamlage B, Pilarsky C, Distler M, Fahlbusch T, Chromik A, Klein F, Bahra M, Uhl W, Grützmann R, Mahajan U M, Weiss F U, Mayerle J, Lerch M M. Gut, 2021, 70: 2150.

[53] Bhalla P, Rengaswamy R, Karunagaran D, Suraishkumar G K, Sahoo S. npj Syst. Biol. Appl., 2022, 8: 1.

[54] Hermanowicz J M, Szymanowska A, Sieklucka B, Czarnomysy R, Pawlak K, Bielawska A, Bielawski K, Kalafut J, Przybyszewska A, Surazynski A, Rivero-Muller A, Mojzych M, Pawlak D. J. Enzyme Inhib. Med. Chem., 2021, 36: 535.

[55] Lu J-W, Ho Y-J, Ciou S-C, Gong Z. Biomedicines, 2017, 5: 58.

[56] Gornowicz A, Szymanowska A, Mojzych M, Czarnomysy R, Bielawski K, Bielawska A. Molecules, 2021, 26: 2045.

[57] Bürtin F, Mullins C S, Linnebacher M. World J. Gastroenterol., 2020, 26: 1394.

[58] Rombouts C, De Spiegeleer M, Van Meulebroek L, Vanhaecke L, De Vos W H. Sci. Rep., 2021, 11: 17249.

[59] Zhu G, Wang Y, Wang W, Shang F, Pei B, Zhao Y, Kong D, Fan Z. Front. Oncol., 2021, 11: 729512.

[60] Rappez L, Stadler M, Triana S, Gathungu R M, Ovchinnikova K, Phapale P, Heikenwalder M, Alexandrov T. Nat. Methods, 2021, 18: 799.

[61] Zang Q, Sun C, Chu X, Li L, Gan W, Zhao Z, Song Y, He J, Zhang R, Abliz Z. Anal. Chim. Acta, 2021, 1155: 338342.

[62] Chen Y, Wang T, Xie P, Song Y, Wang J, Cai Z. Anal. Chim. Acta, 2021, 1184: 339011.

[63] Xie P, Liang X, Song Y, Cai Z. Anal. Chem., 2020, 92: 11341.

[64] Zhang R, Lu W, Yao Y, Tu L, Yu T, Luan T, Chen B. Sci. Total Environ., 2022, 806: 150438.

[65] Wang Z, Cui B, Zhang F, Yang Y, Shen X, Li Z, Zhao W, Zhang Y, Deng K, Rong Z, Yang K, Yu X, Li K, Han P, Zhu Z-J. Anal. Chem., 2019, 91: 2401.

[66] Liu T, Peng F, Yu J, Tan Z, Rao T, Chen Y, Wang Y, Liu Z, Zhou H, Peng J. Anal. Bioanal. Chem., 2019, 411: 5079.

[67] Van Meulebroek L, De Paepe E, Vercruysse V, Pomian B, Bos S, Lapauw B, Vanhaecke L. Anal. Chem., 2017, 89: 12502.

[68] Rombouts C, De Spiegeleer M, Van Meulebroek L, De Vos W H, Vanhaecke L. Anal. Chim. Acta, 2019, 1066: 79.

[69] Di Giovanni N, Meuwis M-A, Louis E, Focant J-F. J. Proteome Res., 2020, 19: 1013.

[70] Erukainure O L, Mansoor S, Chukwuma C I, Oyebode O A, Koorbanally N A, Islam M S. J. Ethnopharmacol., 2021, 279: 114390.

[71] Zhang Y, Gao B, Valdiviez L, Zhu C, Gallagher T, Whiteson K, Fiehn O. Anal. Chem., 2021, 93: 2174.

[72] Barberini L, Restivo A, Noto A, Deidda S, Fattuoni C, Fanos V, Saba L, Zorcolo L, Mussap M J A O T M. Biomed Res. Int., 2019, 7: 727.

[73] Ning W, Qiao N, Zhang X, Pei D, Wang W. Asia Pac. J. Clin. Oncol., 2021, 17: 403.

[74] Igarashi K, Ota S, Kaneko M, Hirayama A, Enomoto M, Katumata K, Sugimoto M, Soga T. J. Chromatogr. A, 2021, 1652: 462355.

[75] Sakurai T, Katsumata K, Udo R, Tago T, Kasahara K, Mazaki J, Kuwabara H, Kawakita H, Enomoto M, Ishizaki T, Nemoto Y, Osaka Y, Nagakawa Y, Sugimoto M, Tsuchida A. Metabolites, 2022, 12: 59.

[76] Udo R, Katsumata K, Kuwabara H, Enomoto M, Ishizaki T, Sunamura M, Nagakawa Y, Soya R, Sugimoto M, Tsuchida A. Sci. Rep., 2020, 10: 21057.

[77] Chen F, Dai X, Zhou C-C, Li K-X, Zhang Y-J, Lou X-Y, Zhu Y-M, Sun Y-L, Peng B-X, Cui W. Gut, 2021, 70: 1.

[78] Sun C, Li T, Song X, Huang L, Zang Q, Xu J, Bi N, Jiao G, Hao Y, Chen Y, Zhang R, Luo Z, Li X, Wang L, Wang Z, Song Y, He J, Abliz Z. Proc. Natl. Acad. Sci. U.S.A., 2019, 116: 52.

[79] Jiang H, Zhang Y, Liu Z, Wang X, He J, Jin H. J. Ethnopharmacol., 2022, 284: 114760.

[80] Karlsson O, Hanrieder J. Arch. Toxicol., 2017, 91: 2283.

[81] Unsihuay D, Mesa Sanchez D, Laskin J. Annu. Rev. Phys. Chem., 2021, 72: 307.

[82] Wang Z, Fu W, Huo M, He B, Liu Y, Tian L, Li W, Zhou Z, Wang B, Xia J, Chen Y, Wei J, Abliz Z. Acta Pharm. Sin. B, 2021, 11: 3665.

[83] Wei Z, Liu X, Cheng C, Yu W, Yi P. Front. Cell Dev. Biol., 2021, 8: 603837.

[84] Eniafe J, Jiang S. Oncogene, 2021, 40: 3351.

[85] Hosomi K, Kiyono H, Kunisawa J. Gut Microbes, 2020, 11: 276.

[86] Hashim N A A, Ab-Rahim S, Suddin L S, Saman M S A, Mazlan M. Mol Clin Oncol, 2019, 11: 3.

[87] Geijsen A J M R, van Roekel E H, van Duijnhoven F J B, Achaintre D, Bachleitner-Hofmann T, Baierl A, Bergmann M M, Boehm J, Bours M J L, Brenner H, Breukink S O, Brezina S, Chang-Claude J, Herpel E, de Wilt J H W, Gicquiau A, Gigic B, Gumpenberger T, Hansson B M E, Hoffmeister M, Holowatyj A N, Karner-Hanusch J, Keski-Rahkonen P, Keulen E T P, Koole J L, Leeb G, Ose J, Schirmacher P, Schneider M A, Schrotz-King P, Stift A, Ulvik A, Vogelaar F J, Wesselink E, van Zutphen M, Gsur A, Habermann N, Kampman E, Scalbert A, Ueland P M, Ulrich A B, Ulrich C M, Weijenberg M P, Kok D E. Int. J. Cancer, 2020, 146: 3256.

[88] Deng L, Ismond K, Liu Z, Constable J, Wang H, Alatise O I, Weiser M R, Kingham T P, Chang D. Cancer Epidemiol. Biomarkers Prev., 2019, 28: 1283.

[89] Ala M., Int. Rev. Immunol., 2021, 1

[90] Kim D J, Yang J, Seo H, Lee W H, Ho Lee D, Kym S, Park Y S, Kim J G, Jang I-J, Kim Y-K, Cho J-Y. Sci. Rep., 2020, 10: 2860.

[91] Hashim N A A, Ab-Rahim S, Ngah W Z W, Nathan S, Ab Mutalib N S, Sagap I, Jamal A R A, Mazlan M. Bioimpacts, 2021, 11: 33.

[92] Zhu Y, Wang L, Nong Y, Liang Y, Huang Z, Zhu P, Zhang Q. Cancer Manag. Res., 2021, 13: 8865.

[93] Hang D., Zeleznik O. A., Lu J., Joshi A. D., Wu K., Hu Z., Shen H., Clish C. B., Liang L., Eliassen A. H., Ogino S., Meyerhardt J. A., Chan A. T., Song M., European Journal of Epidemiology, 2022, https://doi.org/10.1007/s10654-021-00834-5

[94] Song E M, Byeon J-S, Lee S M, Yoo H J, Kim S J, Lee S-H, Chang K, Hwang S W, Yang D-H, Jeong J-Y. Dig. Dis. Sci., 2018, 63: 1229.

[95] Martín-Blázquez A, Díaz C, González-Flores E, Franco-Rivas D, Jiménez-Luna C, Melguizo C, Prados J, Genilloud O, Vicente F, Caba O, Pérez del Palacio J. Sci. Rep., 2019, 9: 20198.

[96] Răchieriu C E D T M E G F S C S M A H N A. Biomolecules, 2021, 11: 417.

[97] Luo Z, Wang H, Lin S, Liao L, Cai L, Zhang X, Tan Y, Shen M. Anal. Bioanal. Chem., 2022, 414: 3483.

[98] Gumpenberger T, Brezina S, Keski-Rahkonen P, Baierl A, Robinot N, Leeb G, Habermann N, Kok D E G, Scalbert A, Ueland P-M, Ulrich C M, Gsur A. Metabolites, 2021, 11: 119.

[99] Casero R A Jr., Stewart T M, Pegg A E. Nat. Rev. Cancer, 2018, 18: 681.

[100] Firestone R S, Feng M, Basu I, Peregrina K, Augenlicht L H, Schramm V L. Sci. Rep., 2021, 11: 8844.

[101] Rioux B, Pinon A, Gamond A, Martin F, Laurent A, Champavier Y, Barette C, Liagre B, Fagnère C, Sol V, Pouget C. Eur. J. Med. Chem., 2021, 222: 113586.

[102] Venkateswaran N, Conacci-Sorrell M. Cell Stress, 2020, 4: 24.

[103] Venkateswaran N, Lafita-Navarro M C, Hao Y-H, Kilgore J A, Perez-Castro L, Braverman J, Borenstein-Auerbach N, Kim M, Lesner N P, Mishra P, Brabletz T, Shay J W, DeBerardinis R J, Williams N S, Yilmaz O H, Conacci-Sorrell M. Genes Dev., 2019, 33: 1236.

[104] Walczak K, Langner E, Szalast K, Makuch-Kocka A, Pożarowski P, Plech T. Molecules, 2020, 25: 1655.

[105] Platten M, Nollen E A A, Röhrig U F, Fallarino F, Opitz C A. Nat. Rev. Drug Discov., 2019, 18: 379.

[106] Choi S.-C., Brown J., Gong M., Ge Y., Zadeh M., Li W., Byron P. C., Michailidis G., Timothy J. G., Mohamadzadeh M., Morel L., Sci. Transl. Med., 2020, 12, eaax2220

[107] Török N, Tanaka M, Vécsei L. Int. J. Mol. Sci., 2020, 21: 9338.

[108] Papadimitriou N, Gunter M J, Murphy N, Gicquiau A, Achaintre D, Brezina S, Gumpenberger T, Baierl A, Ose J, Geijsen A J M R, van Roekel E H, Gsur A, Gigic B, Habermann N, Ulrich C M, Kampman E, Weijenberg M P, Ueland P M, Kaaks R, Katzke V, Krogh V, Bueno-de-Mesquita B, Ardanaz E, Travis R C, Schulze M B, Sánchez M-J, Colorado-Yohar S M, Weiderpass E, Scalbert A, Keski-Rahkonen P. Int. J. Cancer, 2021, 149: 1659.

[109] Zhang H-L, Zhang A-H, Miao J-H, Sun H, Yan G-L, Wu F-F, Wang X-J. RSC Advances, 2019, 9: 3072.

[110] Opitz C A, Patterson L F S, Mohapatra S R, Dewi D L, Sadik A, Platten M, Trump S. Br. J. Cancer, 2020, 122: 30.

[111] Barcherini V, Almeida J, Lopes E A, Wang M, e Silva D M, Mori M, Wang S, Saraiva L, Santos M M M. ChemMedChem, 2021, 16: 250.

[112] Ramos H, Soares M I L, Silva J, Raimundo L, Calheiros J, Gomes C, Reis F, Monteiro F A, Nunes C, Reis S, Bosco B, Piazza S, Domingues L, Chlapek P, Vlcek P, Fabian P, Rajado A T, Carvalho A T P, Veselska R, Inga A, e Melo T M V D P, Saraiva L. Cell Reports, 2021, 35: 108982.

[113] Raimundo L, Espadinha M, Soares J, Loureiro J B, Alves M G, Santos M M M, Saraiva L. Br. J. Pharmacol., 2018, 175: 3947.

[114] Wang S, Dong W, Liu L, Xu M, Wang Y, Liu T, Zhang Y, Wang B, Cao H. Mol. Carcinog., 2019, 58: 1155.

[115] Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, Tuohy K. Eur. J. Nutr., 2018, 57: 1.

[116] Dermadi D., Valo S., Ollila S., Soliymani R., Sipari N., Pussila M., Sarantaus L., Linden J., Baumann M., Nyström M., 2017, 77, 3352

[117] Wang S, Dong W, Liu L, Xu M, Wang Y, Liu T, Zhang Y, Wang B, Cao H. Mol. Carcinog., 2019, 58: 1155.

[118] Fiorucci S, Biagioli M, Zampella A, Distrutti E. Front. Immunol., 2018, 9: 1853.

[119] Fu T, Coulter S, Yoshihara E, Oh T G, Fang S, Cayabyab F, Zhu Q, Zhang T, Leblanc M, Liu S, He M, Waizenegger W, Gasser E, Schnabl B, Atkins A R, Yu R T, Knight R, Liddle C, Downes M, Evans R M. Cell, 2019, 176: 1098.

[120] Zhang H, Xu H, Zhang C, Tang Q, Bi F. Cell Death Discovery, 2021, 7: 207.

[121] Hang S, Paik D, Yao L, Kim E, Trinath J, Lu J, Ha S, Nelson B N, Kelly S P, Wu L, Zheng Y, Longman R S, Rastinejad F, Devlin A S, Krout M R, Fischbach M A, Littman D R, Huh J R. Nature, 2019, 576: 143.

[122] Huang B, Song B-L, Xu C. Nat. Metab., 2020, 2: 132.

[123] Sun H, Zhang H-L, Zhang A-H, Zhou X-H, Wang X-Q, Han Y, Yan G-L, Liu L, Wang X-J. RSC Advances, 2018, 8: 30061.

[124] Sun L, Cai J, Gonzalez F J. Nat. Rev. Gastroenterol. Hepatol., 2021, 18: 335.

[125] Gilbert D C, Chalmers A J, El-Khamisy S F. Br. J. Cancer, 2012, 106: 18.

[126] Palshof J A, Høgdall E V S, Poulsen T S, Linnemann D, Jensen B V, Pfeiffer P, Tarpgaard L S, Brünner N, Stenvang J, Yilmaz M, Nielsen D L. BMC Cancer, 2017, 17: 48.

[127] Ba S, Gao G, Li T, Zhang H. J. Nanobiotechnol., 2021, 19: 407.

[128] Wu J, Wei Z, Cheng P, Qian C, Xu F, Yang Y, Wang A, Chen W, Sun Z, Lu Y. Theranostics, 2020, 10: 10665.

[129] Wang H, Xi Q, Wu G. Cancer Medicine, 201, 5: 1599.

[130] Butler L M, Yuan J-M, Huang J Y, Su J, Wang R, Koh W-P, Ong C-N. npj Precis. Oncol., 2017, 1: 38.

[131] Bardou M, Barkun A N, Martel M. Gut, 2013, 62: 933.

[132] Sánchez-Alcoholado L, Ordóñez R, Otero A, Plaza-Andrade I, Laborda-Illanes A, Medina J A, Ramos-Molina B, Gómez-Millán J, Queipo-Ortuño M I. Int. J. Mol. Sci., 2020, 21: 6782.

[133] Bailly L, Fabre R, Pradier C, Iannelli A. JAMA Surgery, 2020, 155: 395.

[134] Deng J, Yang Y, Zeng Z, Xiao X, Li J, Luan T. Anal. Chem., 2021, 93: 13089.

[135] Mika A, Kobiela J, Pakiet A, Czumaj A, Sokołowska E, Makarewicz W, Chmielewski M, Stepnowski P, Marino-Gammazza A, Sledzinski T. Sci. Rep., 2020, 10: 1954.

[136] Guo S, Wang Y, Zhou D, Li Z. Sci. Rep., 2014, 4: 5959.

[137] Eylem C C, Yilmaz M, Derkus B, Nemutlu E, Camci C B, Yilmaz E, Turkoglu M A, Aytac B, Ozyurt N, Emregul E. Cancer Lett., 2020, 469: 186.

[138] Nam A S, Chaligne R, Landau D A. Nat. Rev. Genet., 2021, 22: 3.

[139] Vasaikar S V, Straub P, Wang J, Zhang B. Nucleic Acids Res., 2018, 46: D956.