ONCOLOGY / BASIC RESEARCH
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5 (growth arrest-specific transcript 5) lncRNA in non-small cell lung cancer (NSCLC) patients and its association with clinicopathological characteristics.

Material and methods:
Expression pattern of circulating GAS5 was analyzed in 58 plasma samples of NSCLC patients, and 15 healthy controls. Quantitative assessment was performed using the real-time PCR method and TaqMan chemistry.

Results:
Circulating GAS5 expression level in NSCLC patients was not significantly decreased compared to control samples (p = 0.081). Statistically significant difference in GAS5 expression was found in relation to TNM stage of the tumor (p < 0.001), decreasing with progression of the tumor stage. Lower GAS5 expression was detected in patients with larger tumors (p = 0.006), and in patients with lymph node metastasis (p = 0.001). Receiver operating characteristic curve analysis was used to evaluate the diagnostic potential of circulating GAS5 expression, showing the highest predictive power in distinguishing between stage III/IV patients and control samples (AUC = 0.8; sensitivity 53%, specificity 93%), and also for separating patients between TNM stage I/II and stage III/IV (AUC = 0.82; sensitivity 73%, specificity 79%).

Conclusions:
Our study suggests that decreased expression of circulating GAS5 is closely related to the tumor size and TNM stage. Therefore the measurement of GAS5 expression level in plasma could be a promising noninvasive diagnostic molecular biomarker in NSCLC patients.
REFERENCES (25)
1.
Ettinger DS, Akerley W, Bepler G, et al. Non-small cell lung cancer. J Natl Compr Cancer Netw 2010; 8: 740-801.
 
2.
Goldstraw P, Ball D, Jett JR, et al. Non-small-cell lung cancer. Lancet 2011; 378: 1727-40.
 
3.
DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics. CA Cancer J Clin 2014; 64: 252-71.
 
4.
Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet 2013; 382: 720-31.
 
5.
Rapisuwon S, Vietsch EE, Wellstein A. Circulating biomarkers to monitor cancer progression and treatment. Comput Struct Biotechnol J 2016; 4: 211-22.
 
6.
Jiang L, Hong L, Yang W, Zhao Y, Tan A, Li Y. Co-expression network analysis of the lncRNAs and mRNAs associated with cervical cancer progression. Arch Med Sci 2019; 15: 754-64.
 
7.
Gasic V, Stankovic B, Zukic B, 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: 292-8.
 
8.
Peng Z, Zhang C, Duan C. Functions and mechanisms of long noncoding RNAs in lung cancer. Onco Targets Ther 2016; 9: 4411-24.
 
9.
Xu R, Han Y. Long non-coding RNA FOXF1 adjacent non-coding developmental regulatory RNA inhibits growth and chemotherapy resistance in non-small cell lung cancer. Arch Med Sci 2019; 15: 1539-46.
 
10.
Schmitz SU, Grote P, Herrmann BG. Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci 2016; 73: 2491-509.
 
11.
Fila M, Pawłowska E, Blasiak J. Mitochondria in migraine pathophysiology – does epigenetics play a role? Arch Med Sci 2019; 15: 944-56.
 
12.
Liu X, Wang M, Cui Y. LncRNA TP73-AS1 interacted with miR-141-3p to promote the proliferation of non-small cell lung cancer. Arch Med Sci 2019; 15: 1547-54.
 
13.
Liu H, Zhang Q, Lou Q, et al. Differential analysis of lncRNA, miRNA and mRNA expression profiles and the prognostic value of lncRNA in esophageal cancer. Pathol Oncol Res 2020; 26: 1029-39.
 
14.
Hu X, Bao J, Wang Z, et al. The plasma lncRNA acting as fingerprint in non-small-cell lung cancer. Tumour Biol 2016; 37: 3497-504.
 
15.
Lin Y, Leng Q, Zhan M, Jiang F. A plasma long noncoding RNA signature for early detection of lung cancer. Transl Oncol 2018; 11: 1225-31.
 
16.
Liang W, Lv T, Shi X, et al. Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of non-small cell lung cancer. Medicine (Baltimore) 2016; 95: e4608.
 
17.
Tan Q, Zuo J, Qiu S, et al. Identification of circulating long non-coding RNA GAS5 as a potential biomarker for non-small cell lung cancer diagnosis, long non-coding RNA, plasma, GAS5, biomarker. Int J Oncol 2017; 50: 1729-38.
 
18.
Williams GT, Mourtada-Maarabouni M, Farzaneh F. A critical role for non-coding RNA GAS5 in growth arrest and rapamycin inhibition in human T-lymphocytes. Biochem Soc Trans 2011; 39: 482-6.
 
19.
Fleming JV, Hay SM, Harries DN, Rees WD. Effects of nutrient deprivation and differentiation on the expression of growth-arrest genes (gas and gadd) in F9 embryonal carcinoma cells. Biochem J 1998; 330: 573-9.
 
20.
Ma C, Shi X, Zhu Q, et al. The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers. Tumour Biol 2016; 37: 1437-44.
 
21.
Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog 2015; 54: E1-12.
 
22.
Wu Y, Lyu H, Liu H, Shi X, Song Y, Liu B. Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer. Sci Rep 2016; 6: 31093.
 
23.
Dong L, Li G, Li Y, Zhu Z. Upregulation of long noncoding RNA GAS5 inhibits lung cancer cell proliferation and metastasis via miR-205/PTEN axis. Med Sci Monit 2019; 25: 2311-9.
 
24.
Laurent LC, Abdel-Mageed AB, Adelson PD, et al. Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium. J Extracell Vesicles 2015; 4: 26533.
 
25.
Kamel LM, Atef DM, Mackawy AMH, Shalaby SM, Abdelraheim N. Circulating long non-coding RNA GAS5 and SOX2OT as potential biomarkers for diagnosis and prognosis of non-small cell lung cancer. Biotechnol Appl Biochem 2019; 66: 634-42.
 
eISSN:1896-9151
ISSN:1734-1922
Journals System - logo
Scroll to top