الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Summary
Lung cancer is an important public health problem. It accounted for 17% and 9% of all cancers among males and females, respectively and representing 19% of all cancer-related deaths. In Egypt, the 4th most common cancer in male (8.2%) is lung cancer representing nearly 5.7% of all cancers among both Sexes.
It is divided histologically into small cell lung cancer and non-small cell lung cancer (70-80%) which is further subdivided into adenocarcinoma, squamous cell lung cancer and large cell lung cancer.
Nowadays, exosomes were discovered, they were referred to as vesicles ranging from 40–100-nm released as a result of multivesicular endosome (MVE) fusion with the plasma membrane. It contains various types of molecules as proteins, MHC, lncRNA, miRNA, lipids. Their main function was intercellular communication and transfer of molecules between cells. The attention was paid to exosomes because of their important role in cancer development, angiogenesis, progression and metastasis, which make exosomes an important therapeutic target for cancer.
In this study, we detected the role of RAB27A mRNA and LncRNA RP11-510M2.10 obtained from serum exosomes in the non-small cell lung cancer.
By applying real time PCR using SYBER green, differential expression of RAB27A mRNA and LncRNA RP11-510M2.10 were detected. It was found that there was highly statistical difference in the differential expression of RAB27A mRNA among study groups where the mean rank was 29.5 among malignant group, 14.5 among COPD and 8.5 among controls.
ROC curve was constructed to determine the best cutoff value for serum exosomal RAB27A mRNA (RQ value) to discriminate the malignant group from the control groups. Accordingly, the best cutoff value for serum exosomal RAB27A mRNA (RQ value) was ≥ 2.51. The AUC was 0.950. By applying this cutoff value, the overall sensitivity was 95% and the specificity was 100%, positive predictive value 100%, negative predictive value 95.24 % and accuracy 97.5%.
As regard to LncRNA -RP11-510M2.10, it was found that there was highly statistical difference in its differential expression where the mean rank was 12.15 among malignant group, 25.30 among COPD and 32.40 among controls.
ROC curve was constructed to determine the best cutoff value for serum exosomal Lnc-RNA -RP11-510M2.10 (RQ value) to discriminate the malignant group from the control groups. Accordingly, the best cutoff value for serum exosomal Lnc-RNA -RP11-510M2.10 (RQ value) was ≤ 0.745. The AUC was 0.918. By applying this cutoff value, the overall sensitivity was 95% and the specificity was 90%, positive predictive value 90.48%, negative predictive value 94.74 % and accuracy 92.5%.
from both ROC curve, we obtained the positivity rate of serum exosomal investigated biomarkers among the different study groups Concerning serum exosomal RAB27A mRNA, no. of cases ≥ cut off (≥ 2.51) = positive cases were 19/20 representing 95% of the malignant group (P=0.00, <0.01).
Concerning serum exosomal Lnc-RNA-RP11-510M2.10, no. of cases ≤ cut off (≤ 0.745) = positive cases (n=21) representing 95% of the malignant group (n=20), 10% of COPD group (n=10) and 10% of the control group (n=10), (P=0.00, <0.01).
There was a highly statistical significance (P=0.00, <0.01) negative correlation between both markers among all study groups.
Also, bronchoalveolar lavage (BAL) sample were collected from some malignant group patients to detect correlation between the two malignant BAL samples and control ones, and to confirm that our results were attributed to lung cancer, there was a highly statistical significance (P=0.00, <0.01) positive correlation between serum exosomal and BAL exosomal RAB27A mRNA expression among malignant group.
Combined serum exosomal RAB27A mRNA and LncRNA RP11-510M2.10 showed 100% sensitivity, 90% specificity, 90.91%, positive predictive value, 100% negative predictive value and 95% accuracy.
Hence, this study suggests that serum exosomal RAB27A mRNA and LncRNA RP11-510M2.10 (RQ value) may serve as a potential diagnostic biomarker for lung cancer, and introduces it as a novel non-invasive marker for diagnosis of lung cancer.