The Effect of Thiol-Disulfide Homeostasis on Prognosis in Patients with Early-Stage Non-Small Cell Lung Cancer

Abstract

Objective: Lung cancer has a poor prognosis. Thiol groups with high antioxidant capacity are converted to disulfide bonds through biochemical reactions that neutralize different oxidant compounds. The thiol-disulfide (SH-SS) homeostasis has significant effects on cell mechanisms, transcription, and apoptosis. Here we present the prognostic role of dynamic SH-SS homeostasis in patients operated for NSCLC. Materials and Methods: Patients operating for early-stage NSCLC were prospectively analyzed. SH-SS homeostasis tests were measured using the automated spectrophotometric method. Results: This study enrolled 138 subjects, including 77 patients and 61 healthy controls. Native thiol and total thiol levels were significantly lower in the patient group. The disulfide-to-native thiol ratio, which is an indicator of oxidative stress in SH-SS homeostasis, also reached a level of statistical significance in the patient group (p<0.001). According to the cut-off values (305 and 326.3), the median overall survival rate was significantly shorter in patients with low native thiol and total thiol levels (p<0.001). Conclusions: This study demonstrated decreased native thiol and total thiol levels as well as decreased disulfide levels and SS/SH ratio in early-stage NSCLC. Impaired SH-SS homeostasis may contribute to lung cancer pathogenesis and poor prognosis because of enhanced oxidative stress.

Keywords

• oxidative stress
• thiol
• disulphide
• NSCLC
• early stage lung cancer

Erken Evre Küçük Hücreli Dışı Akciğer Kanserli Hastalarda Tiyol-Disülfid Homeostazisin Prognoz Üzerine Etkisi

Öz

Amaç: Akciğer kanseri kötü prognoza sahiptir. Antioksidan kapasitesi yüksek olan tiyol grupları, farklı oksidan bileşikleri nötralize eden biyokimyasal reaksiyonlarla disülfid (SS) gruplarına dönüşürler. Tiyol/Disülfid homeostazı (TDH) hücre mekanizmaları, transkripsiyon ve apoptoz üzerinde önemli etkilere sahiptir. KHDAK nedeniyle ameliyat edilen hastalarda dinamik TDH'nin prognozunun rolünü sunuyoruz. Materyal ve Metot: KHDAK ile erken evre opere edilen hastalarda prospektif olarak analiz edildi. TDH testleri otomatik spektrofotometrik yöntemle ölçüldü. Bulgular: Bu çalışmaya 77 hasta, 61 sağlıklı olmak üzere toplam 138 kişi katıldı. Native tiyol (NT) ve total tiyol (TT) düzeyleri hasta grubunda anlamlı olarak düşüktü. TDH'nin oksidatif stres göstergesi olan SS/NT oranı da hastalarda istatistiksel olarak anlamlı bulunmuştur (p<0,001). Medyan OS, NT ve TT düzeyi düşük olan hastalarda cut-off değerine göre (305 ve 326,3) anlamlı olarak daha kısaydı (p<0,001). Sonuç: Bu sonuçlar erken evre KHDAK'de; doğal tiyol ve toplam tiyol seviyeleri azaldığını, disülfid seviyeleri ve disülfid/NT oranının da bozulduğunu göstermektedir. Bozulmuş tiyol/disülfid homeostazı, artan oksidatif stresin bir sonucu olarak akciğer kanseri patogenezine ve kötü prognoza katkıda bulunabilir.

Anahtar Kelimeler

• Disülfid
• erken evre akciğer kanseri
• KHDAK
• oksidatif stres
• tiyol

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