The Differences in Urokinase Plasminogen Activator System in Lung Cancer Patients Before and After Chemotherapy

Authors

  • Tri Wahju Astuti Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya
  • Agustin Iskandar Universitas Brawijaya
  • Mufidatun Hasanah Universitas Brawijaya
  • Lindayanti Sumali Universitas Brawijaya
  • Dian Nugrahenny Universitas Brawijaya

DOI:

https://doi.org/10.36497/jri.v41i4.214

Keywords:

Lung cancer, Chemotherapy, uPA, suPAR, PAI-1

Abstract

Background: Lung cancer is still the leading cause of death for malignancies worldwide. Urokinase plasminogen activator (uPA), its soluble receptor (suPAR), and its inhibitor (PAI-1) play an important role in tumor invasion and metastasis. This study aimed to evaluate the differences in the urokinase plasminogen activator system (uPA, suPAR, and PAI-1) in lung cancer patients before and after chemotherapy.

Methods: This research was an observational analytical study with a cross-sectional design. The subjects were 30, consisting of 17 lung cancer patients before chemotherapy and 13 lung cancer patients after chemotherapy for 4 or 6 cycles. The levels of serum uPA, suPAR, and PAI-1 were measured by enzyme-linked immunosorbent assay (ELISA).

Results: In lung cancer patients before chemotherapy, there were no significant (p>0.05) differences in levels of serum uPA, suPAR, and PAI-1 between patients with stage III and IV. The highest serum uPA and suPAR levels were found in adenocarcinoma cell types and the highest serum PAI-1 level in adenoepidermoid cell types. After chemotherapy, serum suPAR and PAI-1 were significantly (p < 0.05) decreased in lung cancer patients. However, there were no significant (p>0.05) differences in the levels of serum uPA, suPAR, and PAI-1 between patients with chemotherapy responses for stable and progressive diseases.

Conclusion: This study revealed that suPAR and PAI-1 levels were decreased in lung cancer patients who had received chemotherapy. This can occur due to decreased tumor cells activity. 

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Author Biographies

  • Tri Wahju Astuti, Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya
    Program Studi Pulmonologi dan Kedokteran Respirasi Fakultas Kedokteran
  • Agustin Iskandar, Universitas Brawijaya
    Department of Parasitology/Clinical Pathology, Faculty of Medicine
  • Mufidatun Hasanah, Universitas Brawijaya
    Department of Pulmonology, Faculty of Medicine
  • Lindayanti Sumali, Universitas Brawijaya
    Department of Pulmonology, Faculty of Medicine
  • Dian Nugrahenny, Universitas Brawijaya
    Department of Pharmacology, Faculty of Medicine

References

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer. 2013. Available from: http://globocan.iarc.fr, accessed on August 30, 2020.

World Health Organization. Cancer. Geneva: World Health Organization. 2018. Available from: http://www.who.int/news-room/fact-sheets/detail/cancer, accessed on August 30, 2020.

Mason RJ, Broaddus VC, Martin T, King T, Schraufnagel D, Murray J, et al. Murray and Nadel's textbook of respiratory medicine. 5th ed. Philadelphia: Saunders-Elseviers Inc.; 2011.

Binder BR, Mihaly J, Prager GW. uPAR-uPA-PAI-1 interactions and signaling: a vascular biologist’s view. Thromb Haemost 2007;97(3):336-42.

Minisini AM, Fabbro D, Di Loreto C, Pestrin M, Russo S, Cardellino GG, et al. Markers of the uPA system and common prognostic factors in breast cancer. Am J Clin Pathol 2007;128:112-7.

Taubert H, Wu P, Greither T, Kappler M, et al. Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients. Br J Cancer 2010;102(4):731-7.

Barnes PJ. Chronic obstructive pulmonary disease: effects beyond the lungs. PloS Med 2010;7(3):e1000220.

Romer J, Nielsen BS, and Ploug M. The urokinase receptor as a potential target in cancer therapy. Curr Pharm Des 2004;10(19):2359-76.

World Health Organization. Cancer country profiles, 2014. Geneva: World Health Organization. 2014. Available online, http://www.who.int/cancer/country-profiles/idn_en.pdf, accessed on August 31, 2020.

Mandal SK, Singh TT, Sharma TD, and Amrithalingam V. Clinico-pathology of lung cancer in a regional cancer center in Northeastern India. Asian Pac J Cancer Prev 2013;14(12):7277-81.

Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, et al., editors. SEER Cancer Statistics Review, 1975-2014. Bethesda: National Cancer Institute; 2017. Available online, https://seer.cancer.gov/csr/1975_2014/, accessed on August 30, 2020.

Wong MCS, Lao XQ, Ho KF, Goggins WB, and Tse SLA. Incidence and mortality of lung cancer: global trends and association with socioeconomic status. Sci Rep 2017;7(1):14300.

Didkowska J, Wojciechowska U, Mańczuk M, and Łobaszewski J. Lung cancer epidemiology: contemporary and future challenges worldwide. Ann Transl Med 2016;4(8):150.

Kristina SA, Endarti D, Prabandari YS, Ahsan A, and Thavorncharoensap M. Burden of cancers related to smoking among the indonesian population: premature mortality costs and years of potential life lost. Asian Pac J Cancer Prev 2015;16(16):6903-8.

Fosella FV, Komaki R, and Putnam JB. Lung cancer. 1st ed. New York: Springer-Verlag; 2003.

Lee DS, Kim SJ, Kang JH, Hong SH, Jeon EK, Kim YK, et al. Serum carcinoembryonic antigen levels and the risk of whole-body metastatic potential in advanced non-small cell lung cancer. J Cancer 2014;5(8):663-9.

Brambilla E and Lantuejoul S. Histopathology of lung tumors. In: Textbook of Lung Cancer. 2nd ed. Hansen H, editor. London: CRC Press; 2008.

Midthun DE. Early diagnosis of lung cancer. F1000Prime Rep 2013;5:12.

Holst-Hansen C, Hamers MJAG, Johannessen BE, Brünner N, and Stephens RW. Soluble urokinase receptor released from human carcinoma cells: a plasma parameter for xenograft tumour studies. Br J Cancer 1999;81(2):203-11.

Robert C, Bolon I, Gazzeri S, Veyrenc S, Brambilla C, and Brambilla E. Expression of plasminogen activator inhibitors 1 and 2 in lung cancer and their role in tumor progression. Clin Cancer Res 1999;5(8):2094-102.

Werle B, Kotzsch M, Lah TT, Kos J, Gabrijelcic-Geiger D, Spiess E, et al. Cathepsin B, plasminogen activator-inhibitor (PAI-1) and plasminogen activator-receptor (uPAR) are prognostic factors for patients with non-small cell lung cancer. Anticancer Res 2004;24(6):4147-61.

Myrnasari RS, Astuti T, Pratiwi SD. Preliminary Study: Increased Profile of PAI-1 in Lung Cancer Patients Receiving Chemotherapy. J Respir Indo 2018;38(1):48-56.

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Published

2021-11-27

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