Abstract
Amaç: Akciğer, Anjiotensin konverting enzim 2 (ACE-2) reseptörünü en çok bulunduran organlardan birisidir. Literatürde ACE-2 ekspresyonunakciğer kanseri ile ilişkisini gösteren çok az sayıda çalışma bulunmaktadır. Bu çalışmanın amacı, akciğer kanserinde (adenokarsinom ve skuamöz hücreli akciğer karsinomunda) ve sağlıklı akciğer dokusunda ACE-2 ekspresyon düzeyini araştırmaktır.
Gereç ve Yöntem: Dokuz Eylül Üniversitesi Temel Onkoloji Anabilim Dalı Biyoarşivinde bulunan 2013-2014 yılları arasında tanı almış 67 hasta dokusunda immünohistokimya (IHC) yöntemiyle ACE-2 reseptörleri çalışılmıştır. Ekspresyon yüzde (%) olarak ışık mikroskobunda değerlendirilmiştir. Klinik bulgular ile ACE2ekspresyonu sonuçları istatistiksel yöntemle p<0,05 üzerinden değerlendirilmiştir.
Bulgular: Normal doku ile kıyaslandığı zaman akciğer kanserli dokularda ACE-2 ekspresyonunun arttığını kanıtladık. Sağlıklı akciğer dokusunda ortalama ACE-2 ekspresyon yüzdesi %2.24±6.39 (%95 CI: 0.68 – 3.80), tümör dokusunda ortalama ACE-2 ekspresyon yüzdesi 9.52 ±17.14 (%95 CI: 5.34– 13.70) idi, tümör dokusunda ACE-2 ekspresyonunda anlamlı artış gözlendi (p=0.049). Tümör dokusunda ACE-2 ekspresyonu skuamöz hücreli akciğer kanserinde sağlıklı dokuya göre anlamlı olarak arttı (p=0.002) (Normal dokuda: %2.31 ±7.198, Tümöral dokuda: %15.06±21.139). ACE-2 ekspresyonunun ileri evre akciğer adenokarsinomu olgularında erken evredeki olgulara göre daha yüksek olduğu saptanmıştır. ACE-2 ile EFS (Event-Free Survival; Hastalıksız Sağkalım) ve OS (overall Survival; Genel Sağkalım) arasında anlamlı bir ilişki gösterilememiştir.
Sonuç: ACE-2 ekspresyonu akciğer kanseri tümör dokusunda sağlıklı dokuya kıyasla önemli ölçüde artmıştır. Ayrıca, skuamöz hücreli akciğer kanseri ve ileri evre akciğer adenokarsinomunda erken evreye kıyasla artmış ACE-2 ekspresyonu, potansiyel olarak tanısal veya prognostik bir akciğer kanseri biyobelirteci olabileceğini düşünmemize yol açtı. Ancak daha fazla bilimsel çalışmaya ihtiyaç vardır.
Keywords
ACE-2 akciğer kanseri skuamöz hücreli akciğer kanseri akciğer adenokarsinom immunhistokimya.
References
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Abstract
Objective: The lung is one of the organs that contain the most angiotensin-converting enzyme 2 (ACE-2) receptor. There are very few studies in the literature showing the association between ACE-2 expression and lung cancer. This study aims to investigate the expression of ACE-2 in lung cancer (adenocarcinoma and squamous cell lung carcinoma) and healthy lung tissue.
Material and Method: ACE-2 receptors were studied by immunohistochemistry (IHC) method in 67 patient tissues diagnosed between 2013 and 2014 in the Bioarchive of Dokuz Eylul University Department of Basic Oncology. ACE-2 expressions were evaluated under a light microscope. Expression values were expressed as percentages (%). Clinical findings and ACE-2 expression results were evaluated with the statistical method over p<0.05. The Kaplan- Meier test evaluated the effect of ACE-2 expression on lung cancer survival.
Results: We showed that ACE-2 expression was increased in lung cancer tissues compared to healthy tissues. 2.24±6.39 (95% CI: 1.85 – 8.39) in healthy tissue, 9.52 ±17.14 (95% CI: 5.90 – 14.07) in tumor tissue (Wilcoxon test; p=0.049). ACE2 was highly expressed in lung squamous cell carcinoma (LUSC) (p=0.002). (Healthy tissue: 2.31%±7.198%, Tumor tissue: 15.06±21.139%). ACE-2 expression was higher in advanced lung adenocarcinoma cases compared to early-stage cases. There was no significant correlation between ACE-2 and EFS (event-free survival) and OS (overall survival).
Conclusion: ACE-2 expression was significantly increased in lung cancer tumor tissue compared to healthy tissue. Furthermore, increased ACE-2 expression in squamous cell lung cancer and advanced-stage lung adenocarcinoma compared to early-stage led us to suggest it can potentially be a diagnostic or prognostic lung cancer biomarker. However, more scientific studies are needed
References
- Duruisseaux M, Esteller M. Lung cancer epigenetics: From knowledge to applications. Seminars in Cancer Biology. 2018 2018/08/01/; 51:116- 28. doi: 10.1016/j.semcancer.2017.09.005.
- Zhang Y, Simoff MJ, Ost D, Wagner OJ, Lavin J, Nauman B, et al. Understanding the patient journey to diagnosis of lung cancer. BMC Cancer. 2021 Apr 14;21(1):402. doi: 10.1186/s12885-021-08067-1.
- Gupta I, Rizeq B, Elkord E, Vranic S, Al Moustafa AE. SARS-CoV-2 Infection and Lung Cancer: Potential Therapeutic Modalities. Cancers (Basel). 2020 Aug 5;12(8):2186. doi: 10.3390/cancers12082186.
- Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C. The protein expression profile of ACE2 in human tissues. Mol Syst Biol. 2020 Jul;16(7): e9610. doi: 10.15252/msb.20209610.
- Turner AJ. ACE2 Cell Biology, Regulation, and Physiological Functions. The Protective Arm of the Renin Angiotensin System (RAS). 2015:185–9. doi: 10.1016/B978-0-12-801364-9.00025-0.
- Chung MK, Karnik S, Saef J, Bergmann C, Barnard J, Lederman MM, et al. SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. EBioMedicine. 2020 Aug; 58:102907. doi: 10.1016/j.ebiom.2020.102907.
- Samad A, Jafar T, Rafi JH. Identification of angiotensin-converting enzyme 2 (ACE2) protein as the potential biomarker in SARS-CoV-2 infection-related lung cancer using computational analyses. Genomics. 2020 Nov;112(6):4912-4923. doi: 10.1016/j.ygeno.2020.09.002.
- Zhang H, Quek K, Chen R, Chen J, Chen B. Expression of the SAR2- Cov-2 receptor ACE2 reveals the susceptibility of COVID-19 in non-small cell lung cancer. J Cancer. 2020 Jul 9;11(18):5289-5292. doi: 10.7150/ jca.49462.
- Garcia-Garduño TC, Padilla-Gutierrez JR, Cambrón-Mora D, Valle Y. RAAS: A Convergent Player in Ischemic Heart Failure and Cancer. International Journal of Molecular Sciences. 2021;22(13):7106. doi:10.3390/ijms22137106.
- Smith JC, Sausville EL, Girish V, Yuan ML, Vasudevan A, John KM, et al. Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE-2 in the Respiratory Tract. Dev Cell. 2020;53(5):514-29.e3. doi: 10.1016/j.devcel.2020.05.012.
- Pinto BGG, Oliveira AER, Singh Y, Jimenez L, Gonçalves ANA, Ogava RLT, et al. ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19. J Infect Dis. 2020 Jul 23;222(4):556-563. doi: 10.1093/infdis/jiaa332.
- Jose A, Shenoy GG, Sunil Rodrigues G, Kumar NAN, Munisamy M, Thomas L, et al. Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy. Cancers (Basel). 2020 Jul 31;12(8):2121. doi: 10.3390/ cancers12082121.
- Gottschalk G, Knox K, Roy A. ACE2: At the crossroad of COVID-19 and lung cancer. Gene Rep. 2021 Jun; 23:101077. doi: 10.1016/j. genrep.2021.101077.
- Cardenas MG, Oswald E, Yu W, Xue F, MacKerell AD Jr, Melnick AM. The Expanding Role of the BCL6 Oncoprotein as a Cancer Therapeutic Target. Clin Cancer Res. 2017 Feb 15;23(4):885-893. doi: 10.1158/1078- 0432.
- Tong M, Wang J, Jiang N, Pan H, Li D. Correlation between p-STAT3 overexpression and prognosis in lung cancer: A systematic review and meta-analysis. PLoS One. 2017 Aug 10;12(8): e0182282. doi: 10.1371/ journal.pone.0182282.
- Hashiguchi T, Miyoshi H, Nakashima K, Yokoyama S, Matsumoto R, Murakami D, et al. Prognostic impact of GATA binding protein-3 expression in primary lung adenocarcinoma. Hum Pathol. 2017 May; 63:157-164. doi: 10.1016/j.humpath.2017.02.024.
- Chai P, Yu J, Ge S, Jia R, Fan X. Genetic alteration, RNA expression, and DNA methylation profiling of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignancies: a pan-cancer analysis. J Hematol Oncol. 2020 May 4;13(1):43. doi: 10.1186/s13045-020-00883-5.
- Kong Q, Xiang Z, Wu Y, Gu Y, Guo J, Geng F. Analysis of the susceptibility of lung cancer patients to SARS-CoV-2 infection. Mol Cancer. 2020;19(1):80. Published 2020 Apr 28. doi:10.1186/s12943-020- 01209-2.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Araştırma Makaleleri |
| Authors | |
| Publication Date | January 30, 2024 |
| Submission Date | January 17, 2023 |
| Published in Issue | Year 2024 Volume: 9 Issue: 1 |
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