الفهرس 
Immune system and tumors
Cancer stem cells in lung cancer patientsOnly 14 pages are availabe for public view
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Abstract
Non-small cell lung cancer (NSCLC) represents the foremost frequent kind of carcinoma that considers one of the most common cancers within the world. NSCLC consists primarily of glandular carcinoma, epithelial cell malignant neoplastic disease and to a lesser extent large-cell carcinoma. Non-small cell microscopic anatomy accounts for 70–80% of carcinoma diagnosis and it is usually diagnosed at a complicated stage. Although the various treatments are applied to clinical practice, NSCLC patients still have poor survival rates because of the resistance to therapy, which places a large health burden on society. Also, the current understanding of biologic determinants of treatment failure in lung cancer patients is limited and the treatment of refractory or relapsed patients remains a major challenge. Therefore, it is important to find effective tumor markers to judge the prognosis of NSCLC clinically. We have a tendency to analyze twenty NSCLC patients (10, before treatment and 10 after treatment), in addition to healthy control volunteers (n=20). Identification of differentially expressed miRNAs in NSCLC patients versus control was done exploitation microarray. Analysis of CD45-, CD133+ and Epcam+ cancer stem cells CD4, CD8, and IFN-ɣ was done by exploitation flow cytometry. In the present study, there were no statistically significant distinction in age and gender between NSCLC patients (before and after treatment) and healthy management volunteers. CBC analysis showed that there was a marked increase in WBCs count and monocytes, however there was a relative decrease in granulocyte in NSCLC patients before treatment. Additionally, there was no significant difference within the smoking index between control smokers and smokers among carcinoma patients. Furthermore, the parentage of CD133+ and Epcam+ CSCs revealed a significant increase in early diagnosed NSCLC patients compared to healthy control volunteers and these results were related to a marked increase in the numbers of CD4+, CD8+ T-cells populations as well as IFN-ɣ expression in NSCLC patients. Also, the CD4+/CD8+ ratio was reduced in in NSCLC patients compared to healthy control volunteers. After treatment, there was a major decrease in the absolute number and relative percentage of CD133+ and Epcam+ CSCs associated with a marked decrease in the numbers of CD4+ and CD8+ T-cells in NSCLC patients. MiRNAs profile analysis indicated that there were 618 miRNAs that were differentially expressed in NSCLCs patients compared to healthy controls. 618 expressed miRNAs, 270 miRNAs are up-regulated and 348 miRNAs were down-regulated. These findings support that the incidence of lung cancer may collaborate in a dysregulation of miRNAs expression levels in cancer patients compared to healthy individuals. - The expression of four miRNAs was confirmed by RT-qPCR (miRNA-181a, miRNA-21, miRNA-145 and miRNA-155). The results revealed that the expression levels of miRNA-181a, miRNA-145 and miRNA-155 were down-regulated; however, miRNA-21 expression was up-regulated before chemotherapy in NSCLCs patients compared to healthy control volunteers. After chemotherapeutic treatments, the expression level of miRNA-155 was increased in NSCLCs patients in comparison to that of NSCLCs patients without treatment and healthy control volunteers. In conclusion, miRNAs analysis in twenty NSCLC patients and 20 normal samples led to the identification of 4 miRNAs whose expression is significantly dysregulated. The most aberrantly expressed miRNAs are miR-181a, miR-145, miR-21 and miR-155 in NSCLC, as shown by microarray and then confirmed by qRT-PCR. And these findings were correlated with a high number of CD4+ and CD8+ T cells and CD133+ Epcam+ CSCs. In this regard, miRNAs, CD4+ and CD8+ T cells and CD133+ Epcam+ CSCs could be potential biomarkers for the incidence of NSCLC and might predict a response to systemic therapy and prognosis in clinical settings. Conclusions Our findings support the idea that lung cancer may lead to a deregulation of miRNA expression in cancer patients compared to healthy individuals. With the recent advancement in gene profiling techniques, miRNAs in different samples may be used as novel biomarkers in early diagnosis of lung cancer. We used a microarray platform to detect specific miRNA expression in NSCLC patients, verification of the results using next-generation sequencing and real-time PCR will help a better understanding of the specific panel of miRNAs in lung cancer. To the best of our knowledge, this is the first study on Egyptian lung cancer patients using microarray. This can be a good step to determine a specific miRNA expression profile in Egyptian lung cancer patients and guide future studies on the diagnostic role of miRNA in lung cancer. Limitations: This study was limited by the relatively high cost and the small number of patients, future studies on a large scale will provide better identification of the specific miRNA expression profile in different subtypes of lung cancer. This is in addition to the limited scope as all the patients were Egyptians, and miRNA expression might differ in lung cancer patients from other countries and other races.