Nivoi cirkulišuće lncRNA GAS5 kod obolelih od karcinoma prostate: iskustvo jednog centra
Sažetak
Uvod/Cilj. Karcinom prostate (KP) je po učestalosti drugi karcinom u muškoj populaciji. Premda je incidenca obolevanja od KP visoka, kod najvećeg broja bolesnika prognoza je povoljna, sa zadovoljavajućim kvalitetom života dugoročno. Cilj rada bio je da se utvrde razlike u nivoima long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) u plazmi zdravih ispitanika i bolesnika sa KP, kao i između obolelih od KP u različitim prognostičkim stadijumima. Metode. U studiju je bilo uključeno 40 bolesnika sa KP i 20 zdravih osoba (kontrolna grupa). Bolesnici sa KP su, na osnovu prognostičkih kriterijuma American Joint Committee on Cancer, bili podeljeni u dve podgrupe (u svakoj po 20 bolesnika). Podaci o bolesnicima su prikupljeni i analizirani, a lncRNA GAS5 je kvantifikovan korišćenjem metode lančane reakcije polimeraze u realnom vremenu. Statistička analiza podataka izvršena je pomoću programa IBM SPSS Statistics 26.0 (IBM, USA, 2019). Rezultati. Izmereni nivo ekspresije lncRNA GAS5 bio je niži kod obolelih od KP u odnosu na zdrave osobe, mada granično statistički značajan (p = 0,056). Daljom analizom dobijenih podataka, utvrđeno je da razlika u nivou ekspresije lncRNA GAS5 u prvoj podgrupi bolesnika i zdravih osoba nije bila statistički značajna (p = 0,268). Bolesnici iz druge podgrupe imali su značajno niže vrednosti lncRNA GAS5 u odnosu na zdravu populaciju (p = 0,033). Razlika u nivou ekspresije lncRNA GAS5 između bolesnika sa povoljnijom prognozom (Grupa 1) i bolesnika sa lošom prognozom (Grupa 2) nije bila statistički značajna (p = 0,275). U oba slučaja, u Grupi 1 (p = 0,805) i u Grupi 2 (p = 0,454), vrednosti lncRNA GAS5 u plazmi nisu pokazale razliku u odnosu na starost bolesnika (≤ 65 vs. > 65 godina). Zaključak. Jedan od glavnih ciljeva u istraživanju KP je pronalaženje novih i efikasnijih biomarkera. Sprovedeno istraživanje pruža jake dokaze o značaju lncRNAs GAS5 u KP, kao i o povezanosti niskih vrednosti ekspresije lncRNA GAS5 sa lošom prognozom kod različitih tumora.
Reference
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71(3): 209‒49.
2. Rawla P. Epidemiology of Prostate Cancer. World J Oncol 2019; 10(2): 63‒89.
3. Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, et al. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 1994; 54(10): 2577‒81.
4. Houédé N, Rébillard X, Bouvet S, Kabani S, Fabbro-Peray P, Trétarre B, et al. Impact on quality of life 3 years after diagnosis of prostate cancer patients below 75 at diagnosis: an observational case-control study. BMC Cancer 2020; 20(1): 757.
5. Siegel DA, O'Neil ME, Richards TB, Dowling NF, Weir HK. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity - United States, 2001-2017. MMWR Morb Mortal Wkly Rep 2020; 69(41): 1473‒80.
6. Dimakakos A, Armakolas A, Koutsilieris M. Novel tools for Prostate Cancer Prognosis, Diagnosis, and Follow-Up. BioMed Res Int 2014; 2014: 890697.
7. Andriole GL Jr. PSA screening and prostate cancer risk reduction. Urol Oncol 2012; 30(6): 936‒7.
8. Gasic V, Stankovic B, Zukic B, Janic D, Dokmanovic L, Krstovski N, et al. Expression Pattern of Long Non-coding RNA Growth Arrest-specific 5 in the Remission Induction Therapy in Childhood Acute Lymphoblastic Leukemia. J Med Biochem 2019; 38(3): 292‒8.
9. Vesovic N, Tosic N, Karan Djurasevic T, Andrić Z, Zdravković D, Pavlović S, et al. Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients. Arch Med Sci 2020: doi:10.5114/aoms.2020.98815.
10. Yang X, Xie Z, Lei X, Gan R. Long non‑coding RNA GAS5 in human cancer (Review). Oncol Lett 2020; 20(3): 2587‒94.
11. Kornienko AE, Guenzl PM, Barlow DP, Pauler FM. Gene regulation by the act of long non-coding RNA transcription. BMC Biol 2013; 11: 59.
12. Pickard MR, Williams GT. Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA. Genes (Basel) 2015; 6(3): 484‒99.
13. Guzel E, Okyay TM, Yalcinkaya B, Karacaoglu S, Gocmen M, Akcakuyu MH. Tumor suppressor and oncogenic role of long non-coding RNAs in cancer. North Clin Istanb 2019; 7(1): 81‒6.
14. Nadhan R, Dhanasekaran DN. Decoding the Oncogenic Signals from the Long Non-Coding RNAs. Onco 2021; 1(2): 176‒206.
15. Ji J, Dai X, Yeung SJ, He X. The role of long non-coding RNA GAS5 in cancers. Cancer Manag Res 2019; 11: 2729‒37.
16. Weber DG, Casjens S, Brik A, Raiko I, Lehnert M, Taeger D, et al. Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies. Biomark Res 2020; 8: 15.
17. Li J, Wang Y, Zhang CG, Xiao HJ, Xiao HJ, Hu JM, et al. Effect of long non-coding RNA GAS5 on proliferation, migration, invasion and apoptosis of colorectal cancer HT-29 cell line. Cancer Cell Int 2018; 18: 4.
18. Smith CM, Steitz JA. Classification of GAS5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5'-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol 1998; 18(12): 6897‒909.
19. Tan Q, Zuo J, Qiu S, Yu Y, Zhou H, Li N, et al. Identification of circulating long non-coding RNA GAS5 as a potential biomarker for non-small cell lung cancer diagnosis non-small cell lung cancer, long non-coding RNA, plasma, GAS5, biomarker. Int J Oncol 2017; 50(5): 1729‒38.
20. Xue D, Zhou C, Lu H, Xu R, Xu X, He X. LncRNA GAS5 inhibits proliferation and progression of prostate cancer by targeting miR-103 through AKT/mTOR signaling pathway. Tumor Biol 2016; doi: 10.1007/s13277-016-5429-8.
21. Fine SW. Evolution in Prostate Cancer Staging: Pathology Updates From AJCC 8th Edition and Opportunities That Remain. Adv Anat Pathol 2018; 25(5): 327‒32.
22. Liang W, Lv T, Shi X, Liu H, Zhu Q, Zeng J, et al. Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of nonsmall cell lung cancer. Medicine (Baltimore) 2016; 95(37): e4608.
23. du Breuil RM, Patel JM, Mendelow BV. Quantitation of beta-actin-specific mRNA transcripts using xeno-competitive PCR. PCR Methods Appl 1993; 3(1): 57‒9.
24. Han L, Ma P, Liu SM, Zhou X. Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects. Tumor Biol 2016; 37: 6847‒54.
25. Senousy MA, El-Abd AM, Abdel-Malek RR, Rizk SM. Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness. Sci Rep 2021; 11: 2095.
26. Carter G, Miladinovic B, Patel AA, Deland L, Mastorides S, Patel NA. Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus. BBA Clin 2015; 4: 102‒7.
27. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11(6): 426‒37.