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Salivary metabolomics for colorectal cancer detection
abstracts
Annals of Oncology
Table: 147P Study population characteristics
148P
Salivary metabolomics for colorectal cancer detection
H. Kuwabara1, A. Iwabuthi2, R. Soya1, M. Enomoto1, T. Ishizaki1, A. Tsuchida1, Y. Nagakawa1, K. Katsumata1, M. Sugimoto3 1 Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan, 2Center for Health Surveillance and Preventive Medicine, Tokyo Medical University, Tokyo, Japan, 3Research and Development Center for Minimally Invasive Therapies Health Promotion and Preemptive Medicine, Tokyo Medical University, Tokyo, Japan Background: As the worldwide prevalence of colorectal cancer (CRC) is increasing, it is of vital importance to reduce its morbidity and mortality by early detection. Saliva is a noninvasively accessible fluid that potentially reflects both oral and systemic diseases. We report here the investigation and validation of salivary biomarkers to distinguish patients with CRC from those with polyps and healthy controls. Methods: Saliva samples from subjects with CRC, polyps, and healthy controls were collected after 9 hours of fasting, and were split into training and validation data. Capillary electrophoresis-mass spectrometry-based metabolomics was used to quantify numerous hydrophilic metabolites. Results: A total of 2,602 unstimulated saliva samples were collected from 231 subjects with CRC, 99 subjects with polyps, and 2272 subjects with healthy controls. The data
v46 | Biomarkers
were randomly divided into training (n ¼ 1,301) and validation data (n ¼ 1301). Biomarkers for distinguishing subjects with CRC from the others, as well as metabolites that normalize whole saliva concentration were identified. Analysis of these metabolites using machine learning-based artificial intelligence showed a high area under the receiver operating characteristic curve (AUC ¼ 0.876; P < 0.0001) in the training dataset. This combination also showed high AUC values using the validation dataset (AUC ¼ 0.861; P < 0.0001). Saliva samples were also collected multiple times from identical subjects and the robustness of these biomarkers were confirmed. Conclusions: Combinations of salivary metabolites show high potential as a screening tool for CRC. Legal entity responsible for the study: Hiroshi Kuwabara. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
149P
Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
V. Voronova1, K. Peskov1, P. Glybochko2, A. Svistunov2, V. Fomin2, P. Kopylov2, D. Enikeev2, E. Gitel2, A. Ragimov2, E. Poddubskaya2, M. Sekacheva2 1 M&S Decisions LLC, Moscow, Russian Federation, 2I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background: While urine biomarkers are widely used to diagnose bladder cancer (BLC), little is known about plasma protein levels in patients with BLC. The current research is aimed to evaluate diagnostic potential of 13 plasma markers including tumor antigens, inflammatory markers and apolipoproteins (Apo) as well as combinations of thereof. Methods: In total 203 healthy volunteers (HV) and 59 patients with BLC were enrolled into the study. Concentrations of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (ff 19-9), prostate-specific antigen (PSA), beta 2 microglobulin (B2M), human-specific C-reactive protein (hsCRP), D-dimer, cytokeratin 19-fragments (CYFRA 21-1), ApoA1, ApoA2, Apoffl, transthyretin (TTR), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in plasma were measured via ELISA. t-test after log-transformation was used to identify between-group differences in biomarker levels. Diagnostic accuracy of the single biomarkers as well as trained random forest (RF), linear discriminant analysis (LDA) and support vector machine (SVM) classifiers was assessed by ROC analysis. Results: Plasma levels of ApoB, B2M, CA 19-9, CYFRA 21-1, D-dimer, hsCRP, sVCAM-1 and TTR were significantly higher (p-value<0.001) whereas ApoA1 and ApoA2 levels were significantly lower (p-value<0.0005) in patients with BLC vs HV.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz239.058/5577646 by guest on 25 October 2019
in Screening Set. Circulating levels of netrin-1 were evaluated with commercial ELISA kits. Results: In Clinical set, subjects with CRC presented higher levels of serum netrin-1 (513.9 6 22.6 pg/mL) than controls (347.8 6 20.3 pg/mL, p < 0.0001). Similar in Screening set, serum levels of netrin-1 was higher in CRC (644.5 6 37.0 pg/mL), in comparison with controls (407.7 6 14.8 pg/mL, p < 0.0001) and AA (416.5 6 18.5 pg/ mL, p < 0.0001). However, there was no difference between controls and AA (p ¼ 0.752). Compared with the low netrin-1 group, the high group presented increased risk of CRC (Clinical set: OR ¼ 4.300 [95% CI 2.473 – 7.477], p < 0.001); Screening set: OR ¼ 7.731 [95% CI 3.618 – 16.519], p < 0.001). ROC curve of netrin-1 was developed to detect CRC (Clinical set: AUC 0.703 [95% CI 0.636 – 0.770]; Screening set: AUC 0.759 [95% CI 0.680 – 0.837]). Conclusions: It suggests netrin-1 as a potential biomarker in the screening and detection of CRC. Legal entity responsible for the study: The First Affiliated Hospital of Soochow University. Funding: Jiangsu Provincial Key Research and Development Plan (No. BE2018659) and Provincial Key Laboratory Program of Higher Education (No. KJS1867). Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
Table: 147P Study population characteristics
148P
Salivary metabolomics for colorectal cancer detection
H. Kuwabara1, A. Iwabuthi2, R. Soya1, M. Enomoto1, T. Ishizaki1, A. Tsuchida1, Y. Nagakawa1, K. Katsumata1, M. Sugimoto3 1 Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan, 2Center for Health Surveillance and Preventive Medicine, Tokyo Medical University, Tokyo, Japan, 3Research and Development Center for Minimally Invasive Therapies Health Promotion and Preemptive Medicine, Tokyo Medical University, Tokyo, Japan Background: As the worldwide prevalence of colorectal cancer (CRC) is increasing, it is of vital importance to reduce its morbidity and mortality by early detection. Saliva is a noninvasively accessible fluid that potentially reflects both oral and systemic diseases. We report here the investigation and validation of salivary biomarkers to distinguish patients with CRC from those with polyps and healthy controls. Methods: Saliva samples from subjects with CRC, polyps, and healthy controls were collected after 9 hours of fasting, and were split into training and validation data. Capillary electrophoresis-mass spectrometry-based metabolomics was used to quantify numerous hydrophilic metabolites. Results: A total of 2,602 unstimulated saliva samples were collected from 231 subjects with CRC, 99 subjects with polyps, and 2272 subjects with healthy controls. The data
v46 | Biomarkers
were randomly divided into training (n ¼ 1,301) and validation data (n ¼ 1301). Biomarkers for distinguishing subjects with CRC from the others, as well as metabolites that normalize whole saliva concentration were identified. Analysis of these metabolites using machine learning-based artificial intelligence showed a high area under the receiver operating characteristic curve (AUC ¼ 0.876; P < 0.0001) in the training dataset. This combination also showed high AUC values using the validation dataset (AUC ¼ 0.861; P < 0.0001). Saliva samples were also collected multiple times from identical subjects and the robustness of these biomarkers were confirmed. Conclusions: Combinations of salivary metabolites show high potential as a screening tool for CRC. Legal entity responsible for the study: Hiroshi Kuwabara. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
149P
Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
V. Voronova1, K. Peskov1, P. Glybochko2, A. Svistunov2, V. Fomin2, P. Kopylov2, D. Enikeev2, E. Gitel2, A. Ragimov2, E. Poddubskaya2, M. Sekacheva2 1 M&S Decisions LLC, Moscow, Russian Federation, 2I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background: While urine biomarkers are widely used to diagnose bladder cancer (BLC), little is known about plasma protein levels in patients with BLC. The current research is aimed to evaluate diagnostic potential of 13 plasma markers including tumor antigens, inflammatory markers and apolipoproteins (Apo) as well as combinations of thereof. Methods: In total 203 healthy volunteers (HV) and 59 patients with BLC were enrolled into the study. Concentrations of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (ff 19-9), prostate-specific antigen (PSA), beta 2 microglobulin (B2M), human-specific C-reactive protein (hsCRP), D-dimer, cytokeratin 19-fragments (CYFRA 21-1), ApoA1, ApoA2, Apoffl, transthyretin (TTR), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in plasma were measured via ELISA. t-test after log-transformation was used to identify between-group differences in biomarker levels. Diagnostic accuracy of the single biomarkers as well as trained random forest (RF), linear discriminant analysis (LDA) and support vector machine (SVM) classifiers was assessed by ROC analysis. Results: Plasma levels of ApoB, B2M, CA 19-9, CYFRA 21-1, D-dimer, hsCRP, sVCAM-1 and TTR were significantly higher (p-value<0.001) whereas ApoA1 and ApoA2 levels were significantly lower (p-value<0.0005) in patients with BLC vs HV.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz239.058/5577646 by guest on 25 October 2019
in Screening Set. Circulating levels of netrin-1 were evaluated with commercial ELISA kits. Results: In Clinical set, subjects with CRC presented higher levels of serum netrin-1 (513.9 6 22.6 pg/mL) than controls (347.8 6 20.3 pg/mL, p < 0.0001). Similar in Screening set, serum levels of netrin-1 was higher in CRC (644.5 6 37.0 pg/mL), in comparison with controls (407.7 6 14.8 pg/mL, p < 0.0001) and AA (416.5 6 18.5 pg/ mL, p < 0.0001). However, there was no difference between controls and AA (p ¼ 0.752). Compared with the low netrin-1 group, the high group presented increased risk of CRC (Clinical set: OR ¼ 4.300 [95% CI 2.473 – 7.477], p < 0.001); Screening set: OR ¼ 7.731 [95% CI 3.618 – 16.519], p < 0.001). ROC curve of netrin-1 was developed to detect CRC (Clinical set: AUC 0.703 [95% CI 0.636 – 0.770]; Screening set: AUC 0.759 [95% CI 0.680 – 0.837]). Conclusions: It suggests netrin-1 as a potential biomarker in the screening and detection of CRC. Legal entity responsible for the study: The First Affiliated Hospital of Soochow University. Funding: Jiangsu Provincial Key Research and Development Plan (No. BE2018659) and Provincial Key Laboratory Program of Higher Education (No. KJS1867). Disclosure: All authors have declared no conflicts of interest.