الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 111 |  |  |
| | | from | 111 | | |
Abstract
Lung cancer is the major cause of cancer deaths worldwide and has the highest morbidity among all cancers. Cancer, as an incurable and multi-factors disease, is caused by early chromosomal modulation and induces cellular transmutation. LncRNAs in lung cancer can manipulate a variety of signalling pathways and play a crucial role in the initiation and progression of lung cancer disease.
LncRNA GIAT4RA is ubiquitination regulator, it is essential for the progress of lung cancer by suppressing LSH at the protein level. LncRNA GIAT4RA interferes with UCHL3-mediated LSH deubiquintination in a way that is UCHL3-dependent. The expression of lncRNA GIAT4RA trended to be upregulated with the stage of lung cancer.
LncRNA AATBC gene expression was upregulated in various types of cancer tissues. LncRNA AATBC may act as a competitive endogenous to influence the expression of downstream target gene through tumor suppressor miR-1237-3p sponging in NPC or YBX1 scaffold in breast cancer.
LncRNA Sirt1-AS is ncNATs interact and stabilize Sirt1-mRNA. Sirt1 may be act as a tumor suppressor gene in various human and animal malignancies. Sirt1 is crucial for maintaining the heterochromatin architecture in vivo by deacetylating histones.
Mutation of SMARCB1 was repeatedly presented in sinonasal, gastrointestinal and pancreatic cancers, however, rarely noticed in lung cancer.
NSE is a traditional biomarker that directly assesses functional damage to neurons since it is up-regulated to preserve homeostasis when axons are damaged. NSE is important in the detection, monitoring, and prediction of different neuroendocrine tumours, particularly lung carcinoma.
The present study evaluated the expression levels of lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt-AS and SMARCB1 by real-time PCR and NSE enzyme levels by ECLIA as biomarkers in a case-control study with 20 apparently healthy controls, 30 non-cancer patients with chronic inflammatory diseases, and 50 newly diagnosed lung cancer patients and correlated those biomarkers with clinical characteristics of chronic inflammatory and lung cancer patients.
In the present study, expression levels of lncRNA GIAT4RA, lncRNA AATBC and NSE enzyme levels were significantly increased in lung cancer group in comparison to control group, while lncRNA Sirt1-AS gene expression was significantly downregulated in lung cancer group when compared to control group.
Statistical analyses showed that there might be a close correlation between these studied parameters and lung cancer incidence based on these findings, our results appear to suggest a possibility that high levels of the lncRNA GIAT4RA, lncRNA AATBC genes expression, NSE concentrations and lower levels of the lncRNA Sirt1-AS gene expression could be new biomarkers for lung cancer and provide a new concept for understanding the association between lncRNAs and lung cancer incidence.
Our study revealed significant relations between lung cancer stages and each of lncRNA GIAT4RA, as well as lncRNA AATBC.
The present study, SMARCB1 expression was significantly downregulated in chronic inflammatory patients as compared to control group as well as lung cancer patients.
The current study showed significant correlations between lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt-AS, SMARCB1 genes expression and tumor size, lymphnode metastasis, stages, grades, smoking, and gender in lung cancer patients. Furthermore, there were significant correlations between lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt-AS and SMARCB1 genes expression and smoking in chronic inflammatory patients.
This study showed that, ROC curve analysis indicated the validity of using lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt1-AS, NSE enzyme as diagnostic markers for lung cancer patients.
In the present study, survival analysis revealed that lower lncRNA Sirt1-AS gene expression was related to lung cancer patients’ worse disease-free survival and shorter overall survival. Furthermore, higher expression of lncRNA AATBC, SMARCB1 genes expression and NSE enzyme levels predicted poor prognosis and metastasis development in lung cancer patients. These findings suggested that lncRNA Sirt1-AS, lncRNA AATBC, SMARCB1 genes expression and NSE enzyme levels may be considered prognostic indicators for lung cancer.