C. elegans as a Powerful Tool for Cancer Screening
Abstract
:1. Healthcare Utilization for Cancer Screening
1.1. Cancer Statistics
1.2. Cancer Screening Economics
2. Blood Tumor Markers and Liquid Biopsy
3. Multi-Cancer Early Detection (MCED)
3.1. A New Paradigm in Cancer Screening
3.2. Galleri by GRAIL, a Blood-Based MCED Test with Cell-Free DNA (cfDNA)
3.3. Circulating Extracellular Vesicles (EVs) for Early-Stage Multi-Cancer Detection
4. Non-Invasive Early Cancer Detection Using Body Fluids
4.1. Urine as a Biomarker in Cancer
4.2. The Smell of Cancer and Volatile Urinary Compounds
4.3. Electronic Nose (e-Nose)
5. Caenorhabditis elegans as a Powerful Biosensor for Cancer Screening
5.1. Chemotactic Response of C. elegans with Urine Samples
5.2. N-NOSE
5.3. Cancer Type Identification with N-NOSE
5.4. N-NOSE Clinical Research
5.5. Replication of N-NOSE Behavioral Assay by Other Research Groups
6. Conclusions: N-NOSE as a Multi-Cancer Primary Cancer Screening Test
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Cancer Information Service Japan, Cancer Statistics in Japan. Available online: https://ganjoho.jp/public/qa_links/report/statistics/pdf/cancer_statistics_2021.pdf (accessed on 1 August 2022).
- Ebell, M.H.; Thai, T.N.; Royalty, K.J. Cancer screening recommendations: An international comparison of high income countries. Public Health Rev. 2018, 39, 7. [Google Scholar] [CrossRef] [PubMed]
- Ponti, A.; Anttila, A.; Ronco, G.; Senore, C. Cancer Screening in the European Union (2017). Report on the Implementation of the Council Recommendation on Cancer Screening; European Commission: Brussels, Belgium, 2017; p. 333. [Google Scholar]
- World Health Organization. IARC Handbooks of Cancer Prevention. Volume 10: Cervix Cancer Screening; WHO: Geneva, Switzerland, 2005. [Google Scholar]
- Berry, D.A.; Cronin, K.A.; Plevritis, S.K.; Fryback, D.G.; Clarke, L.; Zelen, M.; Mandelblatt, J.S.; Yakovlev, A.Y.; Habbema, J.D.; Feuer, E.J.; et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N. Engl. J. Med. 2005, 353, 1784–1792. [Google Scholar] [CrossRef] [PubMed]
- OECD. Health Care Utilisation. Available online: https://stats.oecd.org/index.aspx?queryid=30159 (accessed on 1 August 2022).
- WHO. W.H.O. Cancer Statistics. Available online: https://www.who.int/news-room/fact-sheets/detail/cancer (accessed on 8 September 2022).
- Knaul, F.M.; Arreola-Ornelas, H.; Rodriguez, N.M.; Mendez-Carniado, O.; Kwete, X.J.; Puentes-Rosas, E.; Bhadelia, A. Avoidable Mortality: The Core of the Global Cancer Divide. J. Glob. Oncol. 2018, 4, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Chen, R.C.; Haynes, K.; Du, S.; Barron, J.; Katz, A.J. Association of Cancer Screening Deficit in the United States with the COVID-19 Pandemic. JAMA Oncol. 2021, 7, 878–884. [Google Scholar] [CrossRef]
- Wernli, K.J.; Brenner, A.T.; Rutter, C.M.; Inadomi, J.M. Risks Associated with Anesthesia Services during Colonoscopy. Gastroenterology 2016, 150, 888–894. [Google Scholar] [CrossRef]
- Brill, J.V. Screening for cancer: The economic, medical, and psychosocial issues. Am. J. Manag. Care 2020, 26, S300–S306. [Google Scholar] [CrossRef]
- Sarhadi, V.K.; Armengol, G. Molecular Biomarkers in Cancer. Biomolecules 2022, 12, 1021. [Google Scholar] [CrossRef]
- Inaba, S.; Shimozono, N.; Yabuki, H.; Enomoto, M.; Morishita, M.; Hirotsu, T.; di Luccio, E. Accuracy evaluation of the C. elegans cancer test (N-NOSE) using a new combined method. Cancer Treat. Res. Commun. 2021, 27, 100370. [Google Scholar] [CrossRef]
- Duffy, M.J. Carcinoembryonic antigen as a marker for colorectal cancer: Is it clinically useful? Clin. Chem. 2001, 47, 624–630. [Google Scholar] [CrossRef]
- Markou, A.; Tzanikou, E.; Lianidou, E. The potential of liquid biopsy in the management of cancer patients. Semin. Cancer Biol. 2022, 84, 69–79. [Google Scholar] [CrossRef]
- Poulet, G.; Massias, J.; Taly, V. Liquid Biopsy: General Concepts. Acta Cytol. 2019, 63, 449–455. [Google Scholar] [CrossRef] [PubMed]
- Ignatiadis, M.; Sledge, G.W.; Jeffrey, S.S. Liquid biopsy enters the clinic—Implementation issues and future challenges. Nat. Rev. Clin. Oncol. 2021, 18, 297–312. [Google Scholar] [CrossRef] [PubMed]
- Shumilov, E.; Flach, J.; Pabst, T.; Fiedler, M.; Angelillo-Scherrer, A.; Trumper, L.; Joncourt, R.; Kohlmann, A.; Bacher, U. Genetic alterations crossing the borders of distinct hematopoetic lineages and solid tumors: Diagnostic challenges in the era of high-throughput sequencing in hemato-oncology. Crit. Rev. Oncol. Hematol. 2018, 126, 64–79. [Google Scholar] [CrossRef] [PubMed]
- Hubbell, E.; Clarke, C.A.; Aravanis, A.M.; Berg, C.D. Modeled Reductions in Late-stage Cancer with a Multi-Cancer Early Detection Test. Cancer Epidemiol. Biomark. Prev. 2021, 30, 460–468. [Google Scholar] [CrossRef]
- Klein, E.A.; Richards, D.; Cohn, A.; Tummala, M.; Lapham, R.; Cosgrove, D.; Chung, G.; Clement, J.; Gao, J.; Hunkapiller, N.; et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann. Oncol. 2021, 32, 1167–1177. [Google Scholar] [CrossRef]
- Pons-Belda, O.D.; Fernandez-Uriarte, A.; Diamandis, E.P. Multi Cancer Early Detection by Using Circulating Tumor DNA-The Galleri Test. Reply to Klein et al. The Promise of Multicancer Early Detection. Comment on “Pons-Belda et al. Can Circulating Tumor DNA Support a Successful Screening Test for Early Cancer Detection? The Grail Paradigm. Diagnostics 2021, 11, 2171”. Diagnostics 2022, 12, 1243. [Google Scholar] [CrossRef]
- Fiala, C.; Diamandis, E.P. A multi-cancer detection test: Focus on the positive predictive value. Ann. Oncol. 2020, 31, 1267–1268. [Google Scholar] [CrossRef]
- Hoshino, A.; Kim, H.S.; Bojmar, L.; Gyan, K.E.; Cioffi, M.; Hernandez, J.; Zambirinis, C.P.; Rodrigues, G.; Molina, H.; Heissel, S.; et al. Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. Cell 2020, 182, 1044–1061.e18. [Google Scholar] [CrossRef]
- Hinestrosa, J.P.; Kurzrock, R.; Lewis, J.M.; Schork, N.J.; Schroeder, G.; Kamat, A.M.; Lowy, A.M.; Eskander, R.N.; Perrera, O.; Searson, D.; et al. Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test. Commun. Med. 2022, 2, 29. [Google Scholar] [CrossRef]
- Bax, C.; Lotesoriere, B.J.; Sironi, S.; Capelli, L. Review and Comparison of Cancer Biomarker Trends in Urine as a Basis for New Diagnostic Pathways. Cancers 2019, 11, 1244. [Google Scholar] [CrossRef] [Green Version]
- Tivey, A.; Church, M.; Rothwell, D.; Dive, C.; Cook, N. Circulating tumour DNA—Looking beyond the blood. Nat. Rev. Clin. Oncol. 2022, 19, 600–612. [Google Scholar] [CrossRef] [PubMed]
- Piqueret, B.; Bourachot, B.; Leroy, C.; Devienne, P.; Mechta-Grigoriou, F.; d’Ettorre, P.; Sandoz, J.C. Ants detect cancer cells through volatile organic compounds. iScience 2022, 25, 103959. [Google Scholar] [CrossRef] [PubMed]
- Lanza, E.; Di Rocco, M.; Schwartz, S.; Caprini, D.; Milanetti, E.; Ferrarese, G.; Lonardo, M.T.; Pannone, L.; Ruocco, G.; Martinelli, S.; et al. C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples. Sci. Rep. 2021, 11, 17133. [Google Scholar] [CrossRef] [PubMed]
- Thompson, M.; Sarabia Feria, N.; Yoshioka, A.; Tu, E.; Civitci, F.; Estes, S.; Wagner, J.T. A Caenorhabditis elegans behavioral assay distinguishes early stage prostate cancer patient urine from controls. Biol. Open 2021, 10, bio057398. [Google Scholar] [CrossRef] [PubMed]
- Daily, A.; Ravishankar, P.; Harms, S.; Klimberg, V.S. Using tears as a non-invasive source for early detection of breast cancer. PLoS ONE 2022, 17, e0267676. [Google Scholar] [CrossRef]
- Wen, Q.; Boshier, P.; Myridakis, A.; Belluomo, I.; Hanna, G.B. Urinary Volatile Organic Compound Analysis for the Diagnosis of Cancer: A Systematic Literature Review and Quality Assessment. Metabolites 2020, 11, 17. [Google Scholar] [CrossRef]
- Saalberg, Y.; Wolff, M. VOC breath biomarkers in lung cancer. Clin. Chim. Acta 2016, 459, 5–9. [Google Scholar] [CrossRef]
- Peng, G.; Hakim, M.; Broza, Y.Y.; Billan, S.; Abdah-Bortnyak, R.; Kuten, A.; Tisch, U.; Haick, H. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br. J. Cancer 2010, 103, 542–551. [Google Scholar] [CrossRef]
- Shirasu, M.; Touhara, K. The scent of disease: Volatile organic compounds of the human body related to disease and disorder. J. Biochem. 2011, 150, 257–266. [Google Scholar] [CrossRef]
- Marzorati, D.; Mainardi, L.; Sedda, G.; Gasparri, R.; Spaggiari, L.; Cerveri, P. A review of exhaled breath: A key role in lung cancer diagnosis. J. Breath Res. 2019, 13, 034001. [Google Scholar] [CrossRef]
- Becker, R. Non-invasive cancer detection using volatile biomarkers: Is urine superior to breath? Med. Hypotheses 2020, 143, 110060. [Google Scholar] [CrossRef] [PubMed]
- Sonoda, H.; Oki, E.; Tanaka, M.; Matsui, T.; Onodera, T.; Toko, K.; Satoh, Y.; Maehara, Y. Research of the Cancer-Odor. Gan Kagaku Ryoho. Cancer Chemother. 2018, 45, 911–915. [Google Scholar]
- Hackner, K.; Errhalt, P.; Mueller, M.R.; Speiser, M.; Marzluf, B.A.; Schulheim, A.; Schenk, P.; Bilek, J.; Doll, T. Canine scent detection for the diagnosis of lung cancer in a screening-like situation. J. Breath Res. 2016, 10, 046003. [Google Scholar] [CrossRef] [PubMed]
- Feil, C.; Staib, F.; Berger, M.R.; Stein, T.; Schmidtmann, I.; Forster, A.; Schimanski, C.C. Sniffer dogs can identify lung cancer patients from breath and urine samples. BMC Cancer 2021, 21, 917. [Google Scholar] [CrossRef]
- Kure, S.; Iida, S.; Yamada, M.; Takei, H.; Yamashita, N.; Sato, Y.; Miyashita, M. Breast Cancer Detection from a Urine Sample by Dog Sniffing: A Preliminary Study for the Development of a New Screening Device, and a Literature Review. Biology 2021, 10, 517. [Google Scholar] [CrossRef]
- Woollam, M.; Teli, M.; Angarita-Rivera, P.; Liu, S.; Siegel, A.P.; Yokota, H.; Agarwal, M. Detection of Volatile Organic Compounds (VOCs) in Urine via Gas Chromatography-Mass Spectrometry QTOF to Differentiate Between Localized and Metastatic Models of Breast Cancer. Sci. Rep. 2019, 9, 2526. [Google Scholar] [CrossRef]
- Mallafre-Muro, C.; Llambrich, M.; Cumeras, R.; Pardo, A.; Brezmes, J.; Marco, S.; Guma, J. Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis. Cancers 2021, 13, 2534. [Google Scholar] [CrossRef]
- Lima, A.R.; Pinto, J.; Carvalho-Maia, C.; Jeronimo, C.; Henrique, R.; Bastos, M.L.; Carvalho, M.; Guedes de Pinho, P. A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers. Cancers 2020, 12, 2017. [Google Scholar] [CrossRef]
- Monteiro, M.; Moreira, N.; Pinto, J.; Pires-Luis, A.S.; Henrique, R.; Jeronimo, C.; Bastos, M.L.; Gil, A.M.; Carvalho, M.; Guedes de Pinho, P. GC-MS metabolomics-based approach for the identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients. J. Cell. Mol. Med. 2017, 21, 2092–2105. [Google Scholar] [CrossRef]
- Giro Benet, J.; Seo, M.; Khine, M.; Guma Padro, J.; Pardo Martnez, A.; Kurdahi, F. Breast cancer detection by analyzing the volatile organic compound (VOC) signature in human urine. Sci. Rep. 2022, 12, 14873. [Google Scholar] [CrossRef]
- Persaud, K.; Dodd, G. Analysis of discrimination mechanisms in the mammalian olfactory system using a model nose. Nature 1982, 299, 352–355. [Google Scholar] [CrossRef]
- Scheepers, M.; Al-Difaie, Z.; Brandts, L.; Peeters, A.; van Grinsven, B.; Bouvy, N.D. Diagnostic Performance of Electronic Noses in Cancer Diagnoses Using Exhaled Breath: A Systematic Review and Meta-analysis. JAMA Netw. Open 2022, 5, e2219372. [Google Scholar] [CrossRef]
- van Geffen, W.H.; Lamote, K.; Costantini, A.; Hendriks, L.E.L.; Rahman, N.M.; Blum, T.G.; van Meerbeeck, J. The electronic nose: Emerging biomarkers in lung cancer diagnostics. Breathe 2019, 15, e135–e141. [Google Scholar] [CrossRef]
- Issitt, T.; Wiggins, L.; Veysey, M.; Sweeney, S.T.; Brackenbury, W.J.; Redeker, K. Volatile compounds in human breath: Critical review and meta-analysis. J. Breath Res. 2022, 16, 024001. [Google Scholar] [CrossRef]
- Ratiu, I.A.; Ligor, T.; Bocos-Bintintan, V.; Mayhew, C.A.; Buszewski, B. Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD. J. Clin. Med. 2020, 10, 32. [Google Scholar] [CrossRef]
- Licht, J.C.; Grasemann, H. Potential of the Electronic Nose for the Detection of Respiratory Diseases with and without Infection. Int. J. Mol. Sci. 2020, 21, 9416. [Google Scholar] [CrossRef]
- Hu, W.; Wu, W.; Jian, Y.; Haick, H.; Zhang, G.; Qian, Y.; Yuan, M.; Yao, M. Volatolomics in healthcare and its advanced detection technology. Nano Res. 2022, 15, 8185–8213. [Google Scholar] [CrossRef]
- Anzivino, R.; Sciancalepore, P.I.; Dragonieri, S.; Quaranta, V.N.; Petrone, P.; Petrone, D.; Quaranta, N.; Carpagnano, G.E. The Role of a Polymer-Based E-Nose in the Detection of Head and Neck Cancer from Exhaled Breath. Sensors 2022, 22, 6485. [Google Scholar] [CrossRef]
- Baldini, C.; Billeci, L.; Sansone, F.; Conte, R.; Domenici, C.; Tonacci, A. Electronic Nose as a Novel Method for Diagnosing Cancer: A Systematic Review. Biosensors 2020, 10, 84. [Google Scholar] [CrossRef]
- Iliff, A.J.; Xu, X.Z.S. C. elegans: A sensible model for sensory biology. J. Neurogenet. 2020, 34, 347–350. [Google Scholar] [CrossRef]
- Girard, L.R.; Fiedler, T.J.; Harris, T.W.; Carvalho, F.; Antoshechkin, I.; Han, M.; Sternberg, P.W.; Stein, L.D.; Chalfie, M. WormBook: The online review of Caenorhabditis elegans biology. Nucleic. Acids Res. 2007, 35, D472–D475. [Google Scholar] [CrossRef]
- Bargmann, C.I. Comparative chemosensation from receptors to ecology. Nature 2006, 444, 295–301. [Google Scholar] [CrossRef]
- Suzuki, M.; Hattori, Y.; Saito, T.; Harada, Y. Pond Assay for the Sensory Systems of Caenorhabditis elegans: A Novel Anesthesia-Free Method Enabling Detection of Responses to Extremely Low Chemical Concentrations. Biology 2022, 11, 335. [Google Scholar] [CrossRef]
- Hirotsu, T.; Sonoda, H.; Uozumi, T.; Shinden, Y.; Mimori, K.; Maehara, Y.; Ueda, N.; Hamakawa, M. A highly accurate inclusive cancer screening test using Caenorhabditis elegans scent detection. PLoS ONE 2015, 10, e0118699. [Google Scholar] [CrossRef]
- Bargmann, C.I.; Hartwieg, E.; Horvitz, H.R. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 1993, 74, 515–527. [Google Scholar] [CrossRef]
- Asai, A.; Konno, M.; Ozaki, M.; Kawamoto, K.; Chijimatsu, R.; Kondo, N.; Hirotsu, T.; Ishii, H. Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer. Oncotarget 2021, 12, 1687–1696. [Google Scholar] [CrossRef]
- Kobayashi, M.; Fujita, A.; Ogawa, T.; Tanisaka, Y.; Mizuide, M.; Kondo, N.; Imaizumi, Y.; Hirotsu, T.; Ryozawa, S. Caenorhabditis elegans as a Diagnostic Aid for Pancreatic Cancer. Pancreas 2021, 50, 673–678. [Google Scholar] [CrossRef]
- Kusumoto, H.; Tashiro, K.; Shimaoka, S.; Tsukasa, K.; Baba, Y.; Furukawa, S.; Furukawa, J.; Niihara, T.; Hirotsu, T.; Uozumi, T. Efficiency of Gastrointestinal Cancer Detection by Nematode-NOSE (N-NOSE). In Vivo 2020, 34, 73–80. [Google Scholar] [CrossRef]
- Kusumoto, H.; Tashiro, K.; Shimaoka, S.; Tsukasa, K.; Baba, Y.; Furukawa, S.; Furukawa, J.; Suenaga, T.; Kitazono, M.; Tanaka, S.; et al. Behavioural Response Alteration in Caenorhabditis elegans to Urine After Surgical Removal of Cancer: Nematode-NOSE (N-NOSE) for Postoperative Evaluation. Biomark. Cancer 2019, 11, 1179299X19896551. [Google Scholar] [CrossRef]
- Media, N.R.C. Using nematodes to sniff out cancer. Nature 2022. Available online: https://www.nature.com/articles/d42473-022-00011-6 (accessed on 1 August 2022).
- Merl, M.Y.; Li, J.; Saif, M.W. The first-line treatment for advanced pancreatic cancer: Highlights from the “2010 ASCO Gastrointestinal Cancers Symposium”, Orlando, FL, USA. 22–24 January 2010. JOP J. Pancreas 2010, 11, 148–150. [Google Scholar]
- Yang, H.; Mou, Y.; Hu, B. Diagnostic Ability of Volatile Organic Compounds in Digestive Cancer: A Systematic Review with Meta-Analysis. Clin. Med. Insights Oncol. 2022, 16, 11795549221105027. [Google Scholar] [CrossRef]
- Ligor, T.; Adamczyk, P.; Kowalkowski, T.; Ratiu, I.A.; Wenda-Piesik, A.; Buszewski, B. Analysis of VOCs in Urine Samples Directed towards of Bladder Cancer Detection. Molecules 2022, 27, 5023. [Google Scholar] [CrossRef]
- Gasparri, R.; Capuano, R.; Guaglio, A.; Caminiti, V.; Canini, F.; Catini, A.; Sedda, G.; Paolesse, R.; Di Natale, C.; Spaggiari, L. Volatolomic urinary profile analysis for diagnosis of the early stage of lung cancer. J. Breath Res. 2022, 16, 046008. [Google Scholar] [CrossRef]
- Abe, T.; Koi, C.; Kohi, S.; Song, K.B.; Tamura, K.; Macgregor-Das, A.; Kitaoka, N.; Chuidian, M.; Ford, M.; Dbouk, M.; et al. Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer. Clin. Gastroenterol. Hepatol. 2020, 18, 1161–1169.e5. [Google Scholar] [CrossRef]
- Ueda, Y.; Kawamoto, K.; Konno, M.; Noguchi, K.; Kaifuchi, S.; Satoh, T.; Eguchi, H.; Doki, Y.; Hirotsu, T.; Mori, M.; et al. Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice. Oncotarget 2019, 10, 5412–5418. [Google Scholar] [CrossRef] [Green Version]
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di Luccio, E.; Morishita, M.; Hirotsu, T. C. elegans as a Powerful Tool for Cancer Screening. Biomedicines 2022, 10, 2371. https://doi.org/10.3390/biomedicines10102371
di Luccio E, Morishita M, Hirotsu T. C. elegans as a Powerful Tool for Cancer Screening. Biomedicines. 2022; 10(10):2371. https://doi.org/10.3390/biomedicines10102371
Chicago/Turabian Styledi Luccio, Eric, Masayo Morishita, and Takaaki Hirotsu. 2022. "C. elegans as a Powerful Tool for Cancer Screening" Biomedicines 10, no. 10: 2371. https://doi.org/10.3390/biomedicines10102371
APA Styledi Luccio, E., Morishita, M., & Hirotsu, T. (2022). C. elegans as a Powerful Tool for Cancer Screening. Biomedicines, 10(10), 2371. https://doi.org/10.3390/biomedicines10102371