Korelasi ekspresi IL-6 dengan STAT3 pada metastasis penderita KNF WHO tipe 3 LMP-1 positif

S. Soehartono, Monika Teresa Prasetyo, Hendradi Surjotomo, Hendy Setyo Yudhanto

Abstract


Latar belakang: Karsinogenesis karsinoma nasofaring sangat kompleks, dan disebabkan oleh interaksi antara infeksi kronis Epstein-Barr Virus (EBV), faktor lingkungan, dan perubahan genetik serta epigenetik. Latent Membrane Protein (LMP)-1 merupakan antigen utama EBV. LMP-1 diyakini menstimulasi ekspresi sitokin yang memengaruhi perilaku sel epitel, salah satunya adalah Interleukin (IL)- 6. IL-6 akan mengaktivasi jalur Signal Transducer and Activator of Transcription (STAT)3. Peningkatan ekspresi IL-6 dan STAT3 memiliki kaitan erat dalam lingkungan mikro tumor KNF, namun peran IL-6 dan STAT3 dalam modulasi migrasi dan invasi sel KNF masih belum jelas diketahui. Tujuan: Mengetahui korelasi antara ekspresi IL-6 dan ekspresi STAT3 di jaringan nasofaring dengan metastasis penderita KNF WHO tipe III LMP-1 positif. Metode: Penelitian observasional analitik dengan pendekatan cross-sectional yang melibatkan 15 penderita KNF WHO tipe III LMP-1 positif. Pemeriksaan ekspresi LMP-1, IL-6, dan STAT3 menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Penentuan stadium klinis metastasis berdasarkan pemeriksaan klinis dan penunjang radiologis, kemudian dievaluasi nilai TNM menggunakan AJCC 2017. Hasil: Analisis statistik ekspresi IL-6 dan STAT3 menunjukkan korelasi yang signifikan (p=0,020) dengan koefisien korelasi r=0,592. Tidak terdapat perbedaan ekspresi IL-6 yang bermakna di antara penderita stadium III, IVa, dan IVb (p=0,116). Terdapat perbedaan ekspresi STAT3 yang signifikan di antara penderita dengan stadium III, IVa, dan IVb (p=0,038). Kesimpulan: Semakin tinggi ekspresi IL-6 maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif semakin meningkat. Semakin tinggi stadium klinis, maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif akan meningkat. 

Kata kunci: karsinoma nasofaring, Virus Epstein-Barr, LMP-1, IL-6, STAT3 ABSTRACT 

Background:Carcinogenesis of NPC is complex interactions among chronic EBV infection, environmental factors, genetic and epigenetic. LMP-1 is EBV’s antigen most expressed in NPC cases. LMP-1 is believed to stimulate expression of cytokines that affect the behavior of epithelial cells, i.e. Interleukin-6 (IL-6) which will activate the STAT3 pathway. Increased expression of IL-6 and STAT3 has a close relationship in tumor microenvironment of NPC patients, but the role of IL-6 and STAT3 themselves in modulation of migration and invasion of NPC cells are not yet fully understood. Purpose: To find out the correlation between IL-6 expression and STAT3 expression in the nasopharyngeal tissue of NPC patients with LMP-1 positive metastatic WHO type III. Method: Observational analytic study with cross-sectional approach involving 15 patients WHO type III LMP-1 positive NPC patients. Examination of LMP-1, IL-6, and STAT3 using immunohistochemical, and the results were calculated using ImmunoRatio. Clinical staging of metastases based on clinical examination and radiological imaging then synchronized with AJCC 2017. Result: Expressions of IL-6 and STAT3 showed significant correlation (p=0.020) with coefficient r=0.592. There were no differences in IL-6 expression among patients with stage III, IVa, and IVb (p=0.116). There were significant differences in STAT3 expression among patients with stage III, IVa, and IVb (p=0.038). Conclusion: There was a significant positive correlation between IL-6 and STAT3 in tissue from WHO type III LMP-1 positive NPC patients. The higher the clinical stage, the expression of STAT3 in the nasopharyngeal tissue of positive WHO type III LMP-1 NPC patients will increase. 


Keywords


nasopharyngeal carcinoma, Epstein-Barr Virus, LMP-1, IL-6, STAT3

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DOI: https://doi.org/10.32637/orli.v49i20.317

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