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. 2023 Jun 1:11:e15469.
doi: 10.7717/peerj.15469. eCollection 2023.

Clinical diagnostic value of amino acids in laryngeal squamous cell carcinomas

Shousen Hu #  1 , Chang Zhao #  2 , Zi'an Wang  3   4 , Zeyun Li  3   4 , Xiangzhen Kong  3   4
Affiliations

Clinical diagnostic value of amino acids in laryngeal squamous cell carcinomas

Shousen Hu et al. PeerJ. .

Abstract

Background: Early diagnosis and treatment can improve the survival rates of patients with laryngeal squamous cell carcinoma (LSCC). Therefore, it is necessary to discover new biomarkers for laryngeal cancer screening and early diagnosis.

Methods: We collected fasting plasma from LSCC patients and healthy volunteers, as well as cancer and para-carcinoma tissues from LSCC patients, and performed quantitative detection of amino acid levels using liquid chromatography-mass spectrometry. We used overall analysis and multivariate statistical analysis to screen out the statistically significant differential amino acids in the plasma and tissue samples, conducted receiver operating characteristic (ROC) analysis of the differential amino acids to evaluate the sensitivity and specificity of the differential amino acids, and finally determined the diagnostic value of amino acids for laryngeal cancer. Additionally, we identified amino acids in the plasma and tissue samples that are valuable for the early diagnosis of laryngeal cancer classified according to the tumor-node-metastasis (TNM) classification.

Results: Asparagine (Asp) and homocysteine (Hcy) were two amino acids of common significance in plasma and tissue samples, and their specificity and sensitivity analysis showed that they may be new biomarkers for the diagnosis and treatment of LSCC. According to the TNM staging system, phenylalanine (Phe) and isoleucine (Ile) were screened out in the plasma of LSCC patients at early (I and II) and advanced (III and IV) stages; ornithine hydrochloride (Orn), glutamic acid (Glu), and Glycine (Gly) were selected in the tissue. These dysregulated amino acids found in LSCC patients may be useful as clinical biomarkers for the early diagnosis and screening of LSCC.

Keywords: Amino acid; Biomarker; LC-MS; Laryngeal cancer; Staging.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Amino acid profiling of the plasma samples from LSCC patients and NC subjects.
(A) Partial least squares discriminant analysis (PLS-DA) scores between LSCC and NC groups in plasma samples. PC1 and PC2 were the first and second principal components, respectively, and the percentage values represented the proportion of the total variance by each component. (B) The permutation test of PLS-DA model between LSCC and NC groups (n = 100). (C) Overall heatmap of amino acid metabolites in plasma samples. Each section’s colour represents the significance of changes in metabolites (red, up-regulated; blue, down-regulated).
Figure 2
Figure 2. Amino acid profiling of the LSCC and ParaLSCC tissues from LSCC patients.
(A) PLS-DA scores and the permutation test of PLS-DA model between the LSCC and ParaLSCC tissues. (B) The permutation test of PLS-DA model between the LSCC and ParaLSCC tissues (n = 100). (C) Overall heatmap of amino acid metabolites in tissue samples. Each section’s colour represents the significance of changes in metabolites (red, up-regulated; blue, down-regulated).
Figure 3
Figure 3. Commonly different amino acids in plasma and tissue samples.
The quantitative value of Asn and Hcy in plasma samples of LSCC and NC groups (A and B), and in the LSCC and ParaLSCC tissues from LSCC patients (C and D). **P < 0.01, ***P < 0.001.
Figure 4
Figure 4. Receiver operating characteristic (ROC) analysis of two commonly different amino acids in plasma and tissue samples.
ROC analysis of Asn and Hcy, and their combination analysis in plasma samples (A–C) and in tissue samples (D–F). AUC, area under curve.
Figure 5
Figure 5. Amino acid profiling of the plasma and tissue samples between stage I+II and stage III+IV patients according to the TNM staging system.
PLS-DA scores of amino acids in plasma (A) and tissue (B) samples between LSCC stage I+II and stage III+IV patients. Overall heatmap of amino acids in plasma (C) and tissue (D) samples between LSCC stage I+II and stage III+IV patients.
Figure 6
Figure 6. ROC analysis of the different amino acids in plasma and tissue samples between stage I+II and stage III+IV patients.
ROC analysis of Phe and Ile in plasma samples (A–B), and Orn, Glu and Gly in tissue samples (C–E).
See this image and copyright information in PMC

References

    1. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA: A Cancer Journal for Clinicians. 2017;67(2):93–99. doi: 10.3322/caac.21388. - DOI - PubMed
    1. Cadoni G, Giraldi L, Chiarla C, Gervasoni J, Persichilli S, Primiano A, Settimi S, Galli J, Paludetti G, Arzani D, Boccia S, Giovannini I, Almadori G. Prognostic role of serum amino acids in head and neck cancer. Disease Markers. 2020;2020(5):2291759. doi: 10.1155/2020/2291759. - DOI - PMC - PubMed
    1. Chen J, Hou H, Chen H, Luo Y, Zhang L, Zhang Y, Liu H, Zhang F, Liu Y, Wang A, Hu Q. Urinary metabolomics for discovering metabolic biomarkers of laryngeal cancer using UPLC-QTOF/MS. Journal of Pharmaceutical and Biomedical Analysis. 2019;167(7):83–89. doi: 10.1016/j.jpba.2019.01.035. - DOI - PubMed
    1. Figueiredo L, Cole PD, Drachtman RA. Asparaginase Erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase. Expert Review of Hematology. 2016;9(3):227–234. doi: 10.1586/17474086.2016.1142370. - DOI - PubMed
    1. Guibert M, Lepage B, Woisard V, Rives M, Serrano E, Vergez S. Quality of life in patients treated for advanced hypopharyngeal or laryngeal cancer. European Annals of Otorhinolaryngology, Head and Neck Diseases. 2011;128(5):218–223. doi: 10.1016/j.anorl.2011.02.010. - DOI - PubMed

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