A New Field of Application of Saliva Tests for Prognostic Purpose: Focus on Lung Cancer

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Published: Sep 30, 2020
DOI: https://doi.org/10.18097/BMCRM00133
Keywords:
saliva; neuroendocrine cancer; squamous cell carcinoma; adenocarcinoma; prognosis; overall survival; lung cancer; biochemical composition

Main Article Content

L.V. Bel’skaya
Biochemistry Research Laboratory, Omsk State Pedagogical University, 14 Tukhachevsky str, Omsk, 644043 Russia
V.K. Kosenok
Department of Oncology, Omsk State Medical University, 12 Lenina str, Omsk, 644099 Russia

Abstract

The aim of this work was to determine the potential prognostic role of the biochemical parameters of saliva in lung cancer. The study included 425 patients with lung cancer of various histological types. Saliva samples were collected before treatment and 34 biochemical parameters were determined. Prognostic factors were analyzed by multivariate analysis using Cox’s proportional hazard model. Results have shown that for squamous cell carcinoma, LDH activity below 1748 U/L was an independent prognostically unfavorable factor (HR = 2.89; 95% CI 1.28 – 6.46; р = 0.00330). For adenocarcinoma, there was a combination of factors: the content of imidazole compounds above 0.311 mmol/L, seromucoids below 0.098 c.u. and uric acid less than 83 nmol/mL (HR = 7.91; 95% CI 2.52 – 24.11; р = 0.00004). For neuroendocrine lung cancer, an unfavorable prognosis was associated with the urea content below 8 mmol/L, NO below 24 nmol/mL and ALP activity below 74 E/L (HR = 12.50; 95% CI 1.09 – 138.7; р = 0.01184). For radical surgery, an unfavorable prognosis was associated with LDH activity below 545 U/L (HR = 7.20; 95% CI 2.13 – 23.70; p = 0.00968), for combined treatment, with the NO level below 15 nmol/mL (HR = 5.64; 95% CI 1.89 – 16.46; p = 0.02797). The worst prognosis for palliative treatment was observed at the NO level below 24 nmol/mL and the imidazole compound content above 0.311 mmol/L (HR = 2.73; 95% CI 1.07 – 12.92; р = 0.01827). The identified parameters can be used to predict lung cancer and personalized patient’s treatment.

Article Details

How to Cite
Bel’skaya, L., & Kosenok, V. (2020). A New Field of Application of Saliva Tests for Prognostic Purpose: Focus on Lung Cancer. Biomedical Chemistry: Research and Methods, 3(3), e00133. https://doi.org/10.18097/BMCRM00133
Issue
Vol. 3 No. 3 (2020)
Section
CLINICAL STUDIES

References

  1. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, 68(6), 394–424. DOI
  2. Global Burden of Disease Cancer Collaboration. (2019) Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017. A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncology, DOI
  3. Okiror, L., Harling, L., Toufektzian L., King J., Routledge T., Harrison-Phipps K., Pilling, J., Veres, L., Lal, R., Bille, A. (2018) Prognostic factors including lymphovascular invasion on survival for resected non-small cell lung cancer. The Journal of Thoracic and Cardiovascular Surgery, 156(2), 785–93. DOI
  4. Molinier, O., Goupil, F., Debieuvre, D., Auliac, J-B., Jeandeau, S., Lacroix, S., Martin, F. Grivaux, M. (2019) Five-year survival and prognostic factors according to histology in 6,101 Non-Small-Cell Lung Cancer patients. Respir Med Res, 77, 46–54. DOI
  5. Grosu, H.B., Manzanera, A., Shivakumar, S., Sun, S., Gonzalez Graciela, N., Ost, E. (2020) Survival disparities following surgery among patients with different histological types of non-small cell lung cancer. Lung Cancer, 140, 55–8. DOI
  6. Soliman, S.E., Alhanafy, A.M., Habib, M.S.E., Hagag, M., Ibrahem, R.A.L. (2018) Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non-small cell lung cancer. Biochemistry and Biophysics Reports, 15, 45–51. DOI
  7. Sandfeld-Paulsen, B., Aggerholm-Pedersen, N., Bæk, R., Jakobsen, K.R., Meldgaard, P., Folkersen, B.H., Rasmussen, T.R., Varming, K., Jørgensen, M.M., Sorensen, B.S. (2016) Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Molecular Oncology, 10, 1595–602. DOI
  8. Pérez-Ramírez, C., Cańadas-Garre, M., Alnatsha, A., Molina, M.Á., Robles, A.I., Villar, E., Delgado, J.R., Faus-Dáder, M.J., Calleja-Hernández, M.Á. (2017) Interleukins as new prognostic genetic biomarkers in non-small cell lung cancer. Surgical Oncology, 26, 278–85. DOI
  9. Targowski, T., Jahnz-Rozyk, K, Owczarek, W, Raczka, A, Janda, P, Szkoda, T, Płusa, T. (2010) Telomerase activity and serum levels of p53 protein as prognostic factors of survival in patients with advanced non-small cell lung cancer. Respiratory Medicine, 104, 1356–61. DOI
  10. Chen, S., Yan, H., Du, J., Li, J., Shen, B., Ying, H., Zhang, Y., Chen, S. (2018) Prognostic significance of pre-resection albumin/fibrinogen ratio in patients with non-small cell lung cancer: A propensity score matching analysis. Clinica Chimica Acta, 482, 203–8. DOI
  11. Koh, Y.W., Lee, S.J., Park, S.Y. (2017) Prognostic significance of lactate dehydrogenase B according to histologic type of non-small-cell lung cancer and its association with serum lactate dehydrogenase. Pathology – Research and Practice, 213(9), 1134–8. DOI
  12. Hermes, A., Gatzemeier, U., Waschki, B., Reck, M. (2010) Lactate dehydrogenase as prognostic factor in limited and extensive disease stage small cell lung cancer - A retrospective single institution analysis. Respiratory Medicine, 104, 1937–42. DOI
  13. Li, S-J., Lv, W-Y., Du, H., Li, Y-J., Zhang, W-B., Che, G-W., Liu, L.X. (2019) Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database. International Journal of Surgery, 69, 32–42. DOI
  14. Yang, Z., Li, S., Zhao, L., Lv, W., Ju, J., Zhang, W., Li, J., Che, G. (2020) Serum uric acid to lymphocyte ratio: a novel prognostic biomarker for surgically resected early-stage lung cancer. A propensity score matching analysis. Clinica Chimica Acta, 503, 35-44. DOI
  15. Tanriverdi, O., Cokmert, S., Oktay, E., Pilanci, K.N., Menekse, S., Kocar, M., Sen, C.A., Avci, N., Akman, T., Ordu, C., Goksel, G. Meydan, N. (2014) Prognostic significance of the baseline serum uric acid level in non-small cell lung cancer patients treated with first-line chemotherapy: a study of the Turkish Descriptive Oncological Researches Group. Med Oncol, 31(10), 217. DOI
  16. Pietrzak, S., Wojcik, J., Scott, R.J., Kashyap, A., Grodzki, T., Baszuk, P., Bielewicz, M., Marciniak, W., Wójcik, N., Dębniak, T., Masojć, B., Pieróg, J., Cybulski, C., Gronwald, J., Wojtyś, M., Kubisa, B., Sukiennicki, G., Deptuła, J., Waloszczyk, P., Jakubowska, A., Lubiński, J., Lener, M.R. (2019) Influence of the selenium level on overall survival in lung cancer. Journal of Trace Elements in Medicine and Biology, 56, 46–51. DOI
  17. Liu, Y., Gu, X., Lin, Q., Tian, T., Shao, L., Yuan, C., Zhang, B., Fan, K. (2015) Prognostic significance of osteopontin in patients with non-small cell lung cancer: results from a meta-analysis. Int J Clin Exp Med, 8(8), 12765–73.
  18. Ilie, M., Mazure, N.M., Hofman, V., Ammadi, R.E., Ortholan, C., Bonnetaud, C., Havet, K., Venissac, N., Mograbi, B., Mouroux, J., Pouysségur, J., Hofman, P. (2010) High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer. Br J Cancer, 102, 1627–35. DOI
  19. Dehing-Oberije, C., Aerts, H., Yu, S., De Ruysscher, D., Menheere, P., Hilvo, M.,van der Weide, H., Rao, B., Lambin, P. (2011) Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys, 81(2), 360-368. DOI
  20. Gomes, M., Coelho, A., Araujo, A., Azevedo, A., Teixeira, A.L., Catarino, R., Medeiros, R. (2015) IL-6 polymorphism in non-small cell lung cancer: a prognostic value? Tumour Biol, 36, 3679–84. DOI
  21. Sanmamed, M.F., Carranza-Rua, O., Alfaro, C., Onate, C., Martin-Algarra, S., Perez, G., Landazuri, S.F., Gonzalez, A., Gross, S., Rodriguez, I., Muñoz-Calleja, C., Rodríguez-Ruiz, M., Sangro, B., López-Picazo, J.M., Rizzo, M., Mazzolini, G., Pascual, J.I., Andueza, M.P., Perez-Gracia, J.L., Melero I. (2014) Serum interleukin-8 reflects tumor burden and treatment response across malign ancies of multiple tissue origins. Clin Cancer Res, 20, 5697–707. DOI
  22. De Vita, F., Orditura, M., Galizia, G., Romano, C., Roscigno, A., Lieto, E., Catalano, G. (2000) Serum Interleukin-10 Levels as a Prognostic Factor in Advanced Non-small Cell Lung Cancer Patients. CHEST, 117(2), 365–73. DOI
  23. Fiala, O., Pesek, M., Finek, J., Topolcan, O., Racek, J., Minarik, M., Benesova, L., Bortlicek, Z., Poprach, A. Buchler, T. (2015) High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. Tumour Biol, 36, 9215–22. DOI
  24. Machado, D., Marques, C., Dias, M., Campainha, S., Barroso, A. (2019) Inflammatory prognostic biomarkers in advanced non-small cell lung cancer. Pulmonology, 25(3), 181–3. DOI
  25. Zhang, Z.H., Han, Y.W., Liang, H., Wang, L.M. (2015) Prognostic value of serum CYFRA21-1 and CEA for non-small-cell lung cancer. Cancer Med, 4, 1633–8. DOI
  26. Hanagiri, T., Sugaya, M., Takenaka, M., Oka, S., Baba, T., Shigematsu, Y., Nagata, Y., Shimokawa, H., Uramoto, H., Takenoyama, M., Yasumoto, K., Tanaka, F. (2011) Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer. Lung Cancer, 74, 112–7. DOI
  27. Carvalho, S., Troost, E.G.C., Bons, J., Menheere, P., Lambin, P., Oberije, C. (2016) Prognostic value of blood-biomarkers related to hypoxia, inflammation, immune response and tumour load in non-small cell lung cancer – A survival model with external validation. Radiotherapy and Oncology, 119(3), 487–94. DOI
  28. Chiappin, S., Antonelli, G., Gatti, R., De Palo, E.F. (2007) Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clinica Chimica Acta, 383, 30-40. DOI
  29. Punyadeera, C., Slowey, P.D. (2019) Saliva as an emerging biofluid for clinical diagnosis and applications of MEMS/NEMS in salivary diagnostics. Nanobiomaterials in Clinical Dentistry, 22, 543-65. DOI
  30. Roblegg, E., Coughran, A., Sirjani, D. (2019) Saliva: An all-rounder of our body. European Journal of Pharmaceutics and Biopharmaceutics, 142, 133–41. DOI
  31. Bel’skaya, L.V. (2019) Possible applications of saliva for the diagnosis of cancer. Russian Сlinical Laboratory Diagnostics, 64(6), 333-6. DOI
  32. Zhang, L., Xiao, H., Zhou, H., Santiago, S., Lee, J.M., Garon, E.B., Yang, J., Brinkmann, O., Yan, X., Akin, D., Chia, D., Elashoff, D., Park, N., Wong, D.T.W. (2012) Development of transcriptomic biomarker signature in human saliva to detect lung cancer. Cellular and Molecular Life Sciences, 69(19), 3341–50. DOI
  33. Kisluk, J., Ciborowski, M., Niemira, M., Kretowski, A., Niklinski, J. (2014) Proteomics biomarkers for non-small cell lung cancer. Journal of Pharmaceutical and Biomedical Analysis, 101, 40-9. DOI
  34. Sun, Y., Liu, S., Qiao, Z., Shang, Z., Xia, Z., Niu, X., Qian L., Zhang Y., Fan L., Cao C.-X., Xiao H. (2017) Systematic comparison of exosomal proteomes from human saliva and serum for the detection of lung cancer. Anal Chim Acta, 982, 84-95. DOI
  35. Bel’skaya, L.V., Kosenok, V.K., Massard, G. (2016) Endogenous Intoxication and Saliva Lipid Peroxidation in Patients with Lung Cancer. Diagnostics, 6(4), 39. DOI
  36. Bel’skaya, L.V., Kosenok, V.K., Sarf, E.A. (2017) Chronophysiological features of the normal mineral composition of human saliva. Arch. Oral Biol, 82, 286–92. DOI
  37. Dos Santos, D.R., Souza, R.O., Dias, L.B., Ribas, T.B., Farias de Oliveira, L.C., Sumida, D.H., Dornelles, R.C.M., de Melo, A.C., Nakamune, S., Chaves-Neto, A.H. (2018) The effects of storage time and temperature on the stability of salivary phosphatases, transaminases and dehydrogenase. Arch. Oral Biol, 85, 160–5. DOI
  38. Bel’skaya, L.V., Sarf, E.A., Solonenko, A.P. (2019) Morphology of Dried Drop Patterns of Saliva from a Healthy Individual Depending on the Dynamics of Its Surface Tension. Surfaces, 2(2): 395-414. DOI
  39. Bel’skaya, L.V., Kosenok, V.K., Massard, G. (2019) Antioxidant protection system in the saliva of patients with non-small cell lung cancer. Biomedical Chemistry: Research and Methods, 2(1), e00061. DOI
  40. Bel’skaya, L.V., Kosenok, V.K. (2017) The activity of metabolic enzymes in the saliva of lung cancer patients. Natl J Physiol Pharm Pharmacol, 7(6), 646-53. DOI
  41. Savchenko, A.A., Lapeshin, P.V., Dykhno Y.A. (2004) Dependence of the activity of metabolic enzymes of blood lymphocytes in the cells of healthy and tumor lung tissue in patients with lung cancer. Russian Biotherapeutic Journal, 4(3), 70-75. DOI
  42. Wang, Z-X., Yang, L-P., Qiu, M-Z., Wang, Z-Q., Zhou, Y-X., Wang, F., Zhang, D-S., Wang, F-H., Li, Y-H., Xu, R-H. (2016) Prognostic value of preoperative serum lactate dehydrogenase levels for resectable gastric cancer and prognostic nomograms. Oncotarget, 26(7), 945-56. DOI
  43. Yao, F., Zhao, T., Zhong, C., Zhu, J., Zhao, H. (2013) LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma. Tumor Biology, 34, 25-31. DOI
  44. Huijgen, H.J., Sanders, G., Koster, R.W., Vreeken, J., Bossuyt, P. (1997) The clinical value of lactate dehydrogenase in serum: a quantitative review. Eur Clin Chem Clin Biochem, 35(8), 569-79.
  45. Bel’skaya, L.V., Sarf, E.A., Kosenok, V.K. (2018) Correlation interrelations between the composition of saliva and blood plasma in norm. Russian Clinical Laboratory Diagnostics, 63(8), 477-482.
  46. Fleming, M.V., Klimov, V.V., Cherdyntseva, N.V. (2005) On the interaction of allergic reactions and malignant processes. Siberian Oncology Journal, 13(1), 96-101.
  47. Keskinege, A., Elgun, S., Yitmaz, E. (2001) Possible implications of arginase and diamine oxidase in prostatic carcinoma. Cancer Detect. Prev, 25 (1), 76-9.
  48. Manina, I.V., Peretolchina, N.M., Saprykina, N.S., Kozlov, A.M., Mikhailova, I.N., Zhordania, K.I., Barishnikov, A.Y. (2010) Prospects for the use of an H2-histamine receptor antagonist (cimetidine) as an adjuvant of melanoma biotherapy. Immunopathology, allergology, infectology, 4, 42-51.
  49. Faverio, F., Guzzetti, A., Mereghetti, A., Jemoli, R. (1982) Hiperhistaminemia nelle neoplasie della mammilla. Chirurgia Italiana, 34(5), 727-34.
  50. Bel’skaya, L.V., Kosenok, V.K. (2018) The level of sialic acids and imidazole compounds in the saliva of patients with lung cancer of different histological types. Siberian journal of oncology, 17(6), 84-91. DOI
  51. Schuurbiers, O., Meijer, T., Kaanders, J., Looijen-Salamon, M.G., de Geus-Oei, L.F., van der Drift, M.A., van der Heijden, E.H.F.M., Oyen, W.J., Visser, E.P., Span, P.N., Bussink, J. (2014) Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma. J Thorac Oncol., 9, 1485–93. DOI
  52. Swinson, D.E., Jones, J.L., Cox, G., Richardson, D., Harris, A.L., O’Byrne, K.J. (2004) Hypoxia-inducible factor-1 alpha in non-small cell lung cancer: relation to growth factor, protease and apoptosis pathways. Int J Cancer., 111, 43–50. DOI
  53. Stotz, M., Szkandera, J., Seidel, J., Stojakovic, T., Samonigg, H., Reitz, D., Gary, T., Kornprat, P., Schaberl-Moser, R., Hoefler, G., Gerger, A., Pichler, M. (2014) Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients. PLoS One, 9(8), e104730. DOI
  54. Chen, Y.F., Li, Q., Chen, D.T., Pan, J.H., Chen, Y.H., Wen, Z.S., Zeng, W.A. (2016) Prognostic value of pre-operative serum uric acid levels in esophageal squamous cell carcinoma patients who undergo R0 esophagectomy. Cancer Biomark, 17(1), 89–96. DOI
  55. Galunska, B., Paskalev, D., Yankova, T., Chankova, P. (2004) Two-faced Janus biochemistry: uric acid - an oxidant or an antioxidant? Nefrologiya, 4(8), 25–31.
  56. Christen, S., Bifrare, Y., Siegenthaler, C., Leib, S.L., Tauber, M.G. (2001) Marked elevation in cortical urate and xanthine oxidoreductase activity in experimental bacterial meningitis. Brain Res., 900, 244–51.
  57. Kopprash, S., Richter, K., Leonardt, W. (2000) Urate attenuates oxidation of native low-density lipoprotein by hydrochlorite and the subsequent lipoprotein-induced respiratory burst activities of polymorphonuclear leukocytes. Molec Cell Biochem, 206, 51–6.
  58. Malathi, M., Shrinivas, B.R. (2001) Relevance of serum alkaline phosphatase as a diagnostic aid in lung pathology. Indian J Physiol Pharmacol., 45(1), 119–21.
  59. Dokic-Lisanin, M., Pantovic, V., Jovanovic, Z., Samardzic, G., Jurisic, V. (2013) Values of alkaline phosphatase and their isoenzyme profiles in patients with cancer in respect to bone and liver metastasis. Arch. Oncol., 21(1), 14–6. DOI
  60. Bel’skaya, L.V., Kosenok, V.K., Massard, G. (2018) Activity of metabolic enzymes of saliva with neuroendocrine tumors of the lung of various degrees of malignancy. Russian Clinical Laboratory Diagnostics, 63(11), 677–82.
  61. Hussain, S.P., Trivers, G.E., Hofseth, L.J., He, P., Shaikh, I., Mechanic, L.E., Doja, S., Jiang, W., Subleski, J., Shorts, L., Haines, D., Laubach, V.E., Wiltrout, R.H., Djurickovic, D., Harris, C.C. (2004) Nitric oxide, a mediator of inflammation, suppresses tumorigenesis. Cancer Res, 64(19), 6849–53. DOI
  62. Cheng, H., Wang, L., Mollica, M., Re, A.T., Wu, S., Zuo, L. (2014) Nitric oxide in cancer metastasis. Cancer Letters, 353, 1–7. DOI
  63. Chanvorachote, P., Pongrakhananon, V., Chaotham, C. (2016) Roles of nitric oxide on cancer stemness and metastasis in lung cancer cells. Asian journal of pharmaceutical sciences, 11, 24–5. DOI
  64. Thomas, D.D., Heinecke, J.L., Ridnour, L.A., Cheng, R.Y., Kesarwala, A.H., Switzer, C.H., McVicar, D.W., Roberts, D.D., Glynn, S., Fukuto, J.M., Wink, D.A., Miranda, K.M. (2015) Signaling and stress: the redox landscape in NOS2 biology. Free Radic Biol Med, 87, 204–25. DOI
  65. Heinecke, J.L., Ridnour, L.A., Cheng, R.Y., Switzer, C.H., Lizardo, M.M., Khanna, C., Glynn, S.A., Hussain, S.P., Young, H.A., Ambs, S., Wink, D.A. (2014) Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression. Proc Natl Acad Sci USA, 111(17), 6323–8. DOI
  66. Cardnell, R.J., Mikkelsen, R.B. (2011) Nitric oxide synthase inhibition enhances the antitumor effect of radiation in the treatment of squamous carcinoma xenografts. PloS One, 6(5), e20147. DOI