Open Access

Urinary biomarkers for the diagnosis of cervical cancer by quantitative label‑free mass spectrometry analysis

  • Authors:
    • Daranee Chokchaichamnankit
    • Kamolwan Watcharatanyatip
    • Pantipa Subhasitanont
    • Churat Weeraphan
    • Siriporn Keeratichamroen
    • Narongrit Sritana
    • Nuttavut Kantathavorn
    • Penchatr Diskul‑Na‑Ayudthaya
    • Kittirat Saharat
    • Juthamard Chantaraamporn
    • Chris Verathamjamras
    • Natacha Phoolcharoen
    • Kriangpol Wiriyaukaradecha
    • Nilubol Monique Paricharttanakul
    • Wandee Udomchaiprasertkul
    • Thaniya Sricharunrat
    • Chirayu Auewarakul
    • Jisnuson Svasti
    • Chantragan Srisomsap
  • View Affiliations

  • Published online on: April 8, 2019     https://doi.org/10.3892/ol.2019.10227
  • Pages: 5453-5468
  • Copyright: © Chokchaichamnankit et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Due to the invasive procedure associated with Pap smears for diagnosing cervical cancer and the conservative culture of developing countries, identifying less invasive biomarkers is of great interest. Quantitative label‑free mass spectrometry was performed to identify potential biomarkers in the urine samples of patients with cervical cancer. This technique was used to study the differential expression of urinary proteomes between normal individuals and cancer patients. The alterations in the levels of urinary proteomes in normal and cancer patients were analyzed by Progenesis label‑free software and the results revealed that 60 proteins were upregulated while 73 proteins were downregulated in patients with cervical cancer. This method could enrich high molecular weight proteins from 100 kDa. The protein‑protein interactions were obtained by Search Tool for the Retrieval of Interacting Genes/Proteins analysis and predicted the biological pathways involving various functions including cell‑cell adhesion, blood coagulation, metabolic processes, stress response and the regulation of morphogenesis. Two notable upregulated urinary proteins were leucine‑rich α‑2‑glycoprotein (LRG1) and isoform‑1 of multimerin‑1 (MMRN1), while the 3 notable downregulated proteins were S100 calcium-binding protein A8 (S100A8), serpin B3 (SERPINB3) and cluster of differentiation-44 antigen (CD44). The validation of these 5 proteins was performed by western blot analysis and the biomarker sensitivity of these proteins was analyzed individually and in combination with receiver operator characteristic curve (ROC) analysis. Quantitative mass spectrometry analysis may allow for the identification of urinary proteins of high molecular weight. The proteins MMRN1 and LRG1 were presented, for the first time, to be highly expressed urinary proteins in cervical cancer. ROC analysis revealed that LRG1 and SERPINB3 could be individually used, and these 5 proteins could also be combined, to detect the occurrence of cervical cancer.

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Copy and paste a formatted citation
APA
Chokchaichamnankit, D., Watcharatanyatip, K., Subhasitanont, P., Weeraphan, C., Keeratichamroen, S., Sritana, N. ... Srisomsap, C. (2019). Urinary biomarkers for the diagnosis of cervical cancer by quantitative label‑free mass spectrometry analysis. Oncology Letters, 17, 5453-5468. https://doi.org/10.3892/ol.2019.10227
MLA
Chokchaichamnankit, D., Watcharatanyatip, K., Subhasitanont, P., Weeraphan, C., Keeratichamroen, S., Sritana, N., Kantathavorn, N., Diskul‑Na‑Ayudthaya, P., Saharat, K., Chantaraamporn, J., Verathamjamras, C., Phoolcharoen, N., Wiriyaukaradecha, K., Paricharttanakul, N. M., Udomchaiprasertkul, W., Sricharunrat, T., Auewarakul, C., Svasti, J., Srisomsap, C."Urinary biomarkers for the diagnosis of cervical cancer by quantitative label‑free mass spectrometry analysis". Oncology Letters 17.6 (2019): 5453-5468.
Chicago
Chokchaichamnankit, D., Watcharatanyatip, K., Subhasitanont, P., Weeraphan, C., Keeratichamroen, S., Sritana, N., Kantathavorn, N., Diskul‑Na‑Ayudthaya, P., Saharat, K., Chantaraamporn, J., Verathamjamras, C., Phoolcharoen, N., Wiriyaukaradecha, K., Paricharttanakul, N. M., Udomchaiprasertkul, W., Sricharunrat, T., Auewarakul, C., Svasti, J., Srisomsap, C."Urinary biomarkers for the diagnosis of cervical cancer by quantitative label‑free mass spectrometry analysis". Oncology Letters 17, no. 6 (2019): 5453-5468. https://doi.org/10.3892/ol.2019.10227