الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Malignant pleural effusion (MPE) is a frequent complication of advanced NSCLC which severely compromises patient quality of life and significantly shortens the overall survival (OS). Non-small-cell lung cancer (NSCLC) is the most common among all lung malignancies. Moreover, it is the leading cause of cancer related deaths.
MPE can originate from direct and indirect involvement of NSCLC. Direct causes include direct involvement of the pleura or as a result of disrupting the integrity of the lymphatics. An indirect cause of pleural effusion (PE) formation includes increased capillary permeability caused by local inflammatory changes that brought on by tumor invasion. The major risk factors for NSCLC are tobacco smoking, asbestos exposure and genetic predisposition.
To establish the diagnosis of MPE on top of NSCLC, a combined approach should be performed depending on detailed clinical examination, laboratory, pathological and radiological assessment. Standard thoracocentesis is an essential preliminary step to identify the nature of pleural fluid (PF). Exudative effusion in old age dyspneic patients usually raises the suspicion of an underlying malignancy. Accordingly, radiological assessment is mandatory to confirm the presence of a pulmonary mass or to demonstrate other suspicious findings. This goes hand in hand with pathological diagnosis and immunohistochemistry to identify the primary site and verify the histopathological type. Pleural cytology, cell block and pleural biopsy are different modalities for diagnosing MPE. To the moment, pleural biopsy remains the gold standard diagnostic tool with adequate sensitivity. However, it’s considered an invasive procedure.
Circular RNAs (circRNAs) are a member of the noncoding RNAs that exhibit a lot of properties. CircRNAs have a special closed loop structure, and therefore tend to be more stable than linear RNAs and resist degradation by RNases. Mounting evidence has indicated that circRNA expression is altered in various human cancers demonstrating their key role in tumorigenesis. Based on these features, circRNAs can be used as effective biomarkers.
hsa_circ_0067705, a novel circRNA, was found to be upregulated in MPE associated with NSCLC contributing to cancer development and progression. However, a little is documented about how this circRNA regulates the progression of other cancer types. Besides, circRNAs were considered as miRNA sponges. Therefore, it is reasonable to presume that hsa_circ_0067705 might be involved in NSCLC progression despite the fact that the detailed mechanism remains unknown to the current moment.
The aims of the present study were to evaluate the potential role of hsa_circ_0067705 as a novel pleural fluid biomarker for NSCLC diagnosis and to compare between NSCLC-MPE and non-MPE patients regarding the expression level of hsa_circ_0067705.
This study was conducted on PF samples collected from 25 NSCLC patients were confirmed by clinical, radiological and histopathological diagnosis and 25 patients were confirmed by cytology and histopathology to be malignant free effusion having TB or any other condition. Every patient was subjected to complete history taking, physical examination, radiological examination, pathological diagnosis and routine laboratory investigation including liver function tests, renal function tests and complete blood count. PF samples were subjected to routine PF chemical, microscopic and molecular analysis including total RNA extraction and complementary DNA (cDNA) synthesis. Subsequently, relative quantification of hsa_circ_0067705 expression was performed using qRT-PCR.
In the current study, males represented 44% of the NSCLC-MPE patients and 56% of the non-MPE patients. Females represented 56% of NSCLC-MPE and 44% of non-MPE patients. The greater incidence of NSCLC in female gender may be explained by the fact that males tend to have asymptomatic effusion greater than females.
Regarding the smoking status, no statistically significant difference between NSCLC-MPE and non-MPE patients was found (p = 0.244). This may be explained by the fact that smoking is considered an equivalent risk factor for both groups.
As for the clinical manifestations, there was a statistically significant difference between NSCLC-MPE and non-MPE patients regarding cough (p = 0.005). However, no significant difference was found regarding other clinical manifestations (chest pain and weight loss) (p > 0.05).