Eşzamanlı Kemoradyoterapi ile Tedavi Edilen Evre III Küçük Hücreli Dışı Akciğer Kanserli Hastalarda NQO1’in Prognostik Önemi

Yıl 2023, Cilt: 18 Sayı: 1, 67 - 72, 16.03.2023

Celalettin Eroğlu Esin Kiraz Olgun Kontaş Ahmet Öztürk

https://doi.org/10.17517/ksutfd.1063749

Öz

Amaç: Bu çalışmada da eşzamanlı kemoradyoterapi ile tedavi edilen evre III küçük hücreli dışı akciğer kanseri (KHDAK)’li hastalarda NQO1’in prediktif
ve prognostik öneminin tespiti amaçlandı.
Gereç ve Yöntemler: Bu çalışmaya eşzamanlı cisplatin+dosetaksel kemoradyoterapisi ile tedavi edilen evre III 64 KHDAK’li olgu dahil edildi. Hastaların patoloji preparatlarında NQO1 immünohistokimyasal (İHK) boyama yapılarak negatif ve pozitiflik açısından karşılaştırıldı.
Bulgular: Medyan yaş 63 (sınırlar, 35-83) olup olguların %86 (n=55)’sı erkek idi. Olguların %27 (n=17)’si evre IIIA, %56 (n=36)’sı evre IIIB ve %17 (n=11)’si evre IIIC idi. Olgular histopatolojik olarak %47 (n=30) adenokarsinom, %47 (n=47)’si epidermoid karsinom ve %6 (n=4)’sı alt tipi belirlenemeyen KHDAK şeklinde sınıflandı. Medyan takip süresi 20 ay (sınırlar, 3-7 ay) bulundu. NQO1’in İHK boyaması sonucunda olguların 7 (%11)’si negatif, 11 (%17)’i (+) pozitif, 14 (%22)’ü (++) pozitif ve 32 (%50)’si (+++) pozitif olarak bulundu. Olguların NQO1’e göre medyan genel sağkalımı; (-)’lerde 21 ay,
(+)’lerde 19 ay, (++)’lerde 16 ay ve (+++)’lerde 19 ay bulundu. Pozitif NQO1 olan olgularda medyan genel sağkalım sayısal olarak negatif olan olgulardan daha düşük olmasına rağmen istatistiksel olarak anlamlı bulunmadı (p=0.801).
Sonuç: Eşzamanlı kemoradyoterapi ile tedavi edilen evre III KHDAK’li hastalarda NQO1 prognostik faktör olabilir ancak çok hasta sayılı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

KÜÇÜK HÜCRELİ DIŞI AKCİĞER KANSERİ, EŞZAMANLI KEMORADYOTERAPİ, NQO1

Destekleyen Kurum

Erciyes Üniversitesi BAP

Proje Numarası

ID: 8407

Teşekkür

-

Prognostic Impact of NQO1 in Patients with Stage III Non-Small Cell Lung Cancer (NSCLC) Treated with Concomitant Chemoradiotherapy

Öz

Objective: In this study, we aimed to determine the predictive and prognostic value of NQO1 in patients with stage III non-small cell lung cancers (NSCLC) treated with concomitant chemoradiotherapy.
Materials and Methods: 64 patients with stage III NSCLC treated with concomitant cisplatin + docetaxel chemoradiotherapy were enrolled to the study. NQO1 immunohistochemical (IHC) staining was performed on the pathology preparations of the patients and compared in terms of the negative and positivity.
Results: The median age was 63 (range, 35-83 years). Most of the patients (86%, n=55) were male. 27% (n=17) of the patients were stage IIIA, 56% (n=36) were stage IIIB, and 17% (n=11) were stage IIIC. The patients were histopathologically classified as 47% (n=30) adenocarcinoma, 47% (n=30) as epidermoid carcinoma, and 6% (n=4) as NSCLC, Not otherwise specified. Median follow-up was 20 months (range, 3-7 months). As a result of the IHC staining of NQO1, 7 (11%) of the 64 patients were negative, 11 (17%) of the 64 patients were (+) positive, 14 (22%) of the 64 patients were (++) positive and 32 (50%) of the 64 patients were (+++) positive. Median overall survival of patients according to NQO1; was found 21 months in (-)’s, 19 months in (+)’s, 16 months in (++)’s and 19 months in (+++)’s. Although the median overall survival in patients with positive NQO1 was numerically lower than in patients with negative NQO1, which was not statistically significant (p=0.801).
Conclusion: NQO1 may be a prognostic factor in patients with stage III NSCLC treated with concomitant chemoradiotherapy, but further studies with a larger number of patients are needed.

Anahtar Kelimeler

NON SMALL CELL CANCER, CONCOMİTANT CHEMORADİOTHERAPY, NQO1

Proje Numarası

ID: 8407

Kaynakça

• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer istatistics, CA Cancer J Clin. 2021;71:7–33.
• Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383:640–649.
• Jordan AT, Jeffrey MC, Betty CT, and Joseph KS. Non–Small Cell Lung Cancer. In: L.L. Gunderson, J.E. Teper. Clinical Radiation Oncology. 5th ed. Philadelphia, Churchill Livingstone, Elsevier; 2021, p.836-867.
• Jayanthi M K, Prathima C, SubbaRao MVSST. NQO1, Role in Lung Cancer: A Review. J. Pharm. Sci. Res. 2015;7(6):319-323.
• Zhang K, Chen D, Ma K, Wu X, Hao H, Jiang S. NAD(P)H:quinoneoxidoreductase 1 (NQO1) as a therapeutic and diagnostic target in cancer. J MedChem. 2018;61:6983-7003.
• Santanu B. Evaluation of the risk of lung cancer associated with NAD(P)H: quinoneoxidoreductase 1 (NQO1) C609T polymorphism in male current cigarette smokers from the Eastern India. Molecular Biology Research Communications 2020;9(3):111-115.
• Hong Y, Hong-ying G, Hua G, Gui-zhen W, Yi-qing Yang, Qian H et al. Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells. Acta Pharmacologica Sinica 2022;43(3):692-702.
• Garate M, Aijaz AW, Gang L. The NAD(P)H:quinoneoxidoreductase 1 induces cell cycle progression and proliferation of melanoma cells. FreeRadic. Biol. Med. 2010;48:1601–1609.
• Li Z, Zhang Y, Jin T, Men J, Lin Z, Qi P et al. NQO1 protein expression predicts poor prognosis of non-small cell lung cancers. BMC Cancer 2015 Mar 31;15:207.
• Ji M, Jin A, Sun J, Cui X, Yang Y, Chen L et al. Clinicopathological implications of NQO1 overexpression in theprognosis of pancreatic adenocarcinoma. OncolLett. 2017;13(5):2996-3002.
• Liu HY, Li QR, Cheng XF, Wang GJ, Hao HP. NAMPT inhibition synergizes with NQO1-targeting agents in inducing apoptotic cell death in non-small cell lung cancer cells. Chin J NatMed. 2016;14(8):582-589.
• Yen-Chi T, Yu-Jung C, Chun-Hsien W, Linyi C. Discovery of Isoplumbagin as a Novel NQO1 Substrateand Anti-Cancer Quinone. Int. J. Mol. Sci. 2020;21:4378.
• Edward AM, Xiumei H, Naveen S, Jessica K, Noelle W, Xian-Jin X, et al. NQO1-dependent, tumor-selective radiosensitization of non small cell lung cancer. ClinCancerRes. 2019 April 15;25(8):2601–2609.
• Zeekpudsa P, Kukongviriyapan V, Senggunprai L, Sripa B, Prawan A. Suppression of NAD(P)H-quinoneoxidoreductase 1 enhanced the susceptibility of cholangiocarcinoma cells to chemotherapeutic agents. J ExpClinCancerRes. 2014;33:11.
• Özkan K. Akciğer kanserli hastalarda NQO1 gen polimorfizminin araştırılması. Yrd. Doç. Dr. Tammam Sipahi, EDİRNE-2008. (Tez çalışması).