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Metabolomic Profiling of Serum for Large Cohort Oral Squamous Cell Carcinoma Diagnosis
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  • Xihu Yang,
  • Xiaowei Song,
  • Xudong Yang,
  • Wei Han,
  • Yong Fu,
  • Shuai Wang,
  • Xiaoxin Zhang,
  • Guowen Sun,
  • Yong Lu,
  • Zhiyong Wang,
  • Yanhong Ni,
  • Richard Zare,
  • Qingang Hu
Xihu Yang
Medical School of Nanjing University

Corresponding Author:[email protected]

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Xiaowei Song
Fudan University
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Xudong Yang
Medical School of Nanjing University
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Wei Han
Medical School of Nanjing University
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Yong Fu
Medical School of Nanjing University
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Shuai Wang
Medical School of Nanjing University
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Xiaoxin Zhang
Medical School of Nanjing University
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Guowen Sun
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Yong Lu
Medical School of Nanjing University
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Zhiyong Wang
Medical School of Nanjing University
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Yanhong Ni
Medical School of Nanjing University
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Richard Zare
Stanford University
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Qingang Hu
Medical School of Nanjing University
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Abstract

Background: Oral squamous cell carcinoma (OSCC) accounts for 90 % of oral cancers. If a necessary intervention before tumorigenesis could be conducted, the current 60% 5-year survival rate would be expected to be majorly improved. This fact motivates the search for developing a highly sensitive and specific in vitro diagnostic method to conduct rapid OSCC screening. Method: Serum samples from 819 volunteers, consisted of 241 healthy contrast (HC) and 578 OSCC patients, were collected, and their metabolic profiles were acquired using conductive polymer spray ionization mass spectrometry (CPSI-MS). Univariate analysis was used to select significantly changed metabolite ions in the OSCC group compared to the HC group. Identities of these metabolite ions were determined by MS/MS experiments and reconfirmed at the tissue level by desorption electrospray ionization mass spectrometry (DESI-MS). The supporting vector machine (SVM) algorithm was employed as the machine learning model to implement the automatic prediction of OSCC. Results: Through statistical analysis, 65 metabolites were selected as potential characteristic marker candidates for serum OSCC screening. In situ validation by DESI-MSI revealed that 8 out of top 10 metabolites showed the same trends of change in tissue and serum. With the aid of machine learning, OSCC can be distinguished from HC with an accuracy of 98.0 % by cross-validation in the discovery cohort and 89.2% accuracy in the validation cohort. Furthermore, orthogonal partial least square-discriminant analysis (OPLS-DA) also showed the potential for recognizing OSCC stages. Conclusion: Using CPSI-MS combined with SVM, it is possible to distinguish OSCC from HC in a few minutes with high specificity and sensitivity, making this rapid diagnostic procedure a promising approach for high-risk population screening.
09 Aug 2021Submitted to Natural Sciences
10 Aug 2021Submission Checks Completed
10 Aug 2021Assigned to Editor
16 Aug 2021Reviewer(s) Assigned
09 Sep 2021Review(s) Completed, Editorial Evaluation Pending
09 Sep 2021Editorial Decision: Revise Major
24 Sep 20211st Revision Received
28 Sep 2021Submission Checks Completed
28 Sep 2021Assigned to Editor
28 Sep 2021Reviewer(s) Assigned
13 Oct 2021Review(s) Completed, Editorial Evaluation Pending
18 Oct 2021Editorial Decision: Revise Minor
18 Oct 20212nd Revision Received
19 Oct 2021Submission Checks Completed
19 Oct 2021Assigned to Editor
19 Oct 2021Review(s) Completed, Editorial Evaluation Pending
20 Oct 2021Editorial Decision: Accept