Eşzamanlı Kemoradyoterapi ile Tedavi Edilen Evre III Küçük Hücreli Dışı Akciğer Kanserli Hastalarda NQO1’in Prognostik Önemi
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.
Prognostic Impact of NQO1 in Patients with Stage III Non-Small Cell Lung Cancer (NSCLC) Treated with Concomitant Chemoradiotherapy
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.
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- 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).