Assessment of Circulating miRNA-17 and miRNA-222 Expression Profiles as Non-Invasive Biomarkers in Egyptian Patients with Non-Small-Cell Lung Cancer.

Background: Lung cancer is one of the main human health threats. Survival of lung cancer patients depends on the timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs). This study aimed to assess the plasma level of circulating miRNA-17 and miRNA-222 as non-invasive markers in non-small-cell lung cancer (NSCLC) patients. Patients and methods: A total of 40 patients with NSCLC and 20 healthy controls who were matched in terms of age and sex with the patient group were included in this case-control study.. Estimation of miRNA-17 and miRNA-222 expression profiles in the plasma was done using quantitative real-time PCR (qRT-PCR). The relationship between both markers and their clinicopathological features were also determined. Receiver operating characteristic (ROC) curve analysis was done to evaluate the role of these microRNAs in NSCLC diagnosis and follow-up. Results: MiRNA-17 and miRNA-222 levels were significantly upregulated in NSCLC patients compared with controls (48.32±12.35 vs 1.16±0.19 and 34.53±3.1 vs 1.22±0.14) (P=0.000). Plasma miRNA-17 level was increased, and the miRNA-222 level was decreased across different stages of the disease; however, these differences d were not statistically significant (P=0.4, P=0.5, respectively). The miRNA-17 levels were higher in the lung cancer patients with metastasis , but miRNA-222 levels were lower patients without metastasis. We found no statistically significant difference in this regard(P=0.4 vs P=0.3, respectively). ROC curve analysis showed that the sensi¬tivity and specificity of miRNA-17 were 77.78% and 87.50% , and of miRNA-222 were 50% and 88.89%. Conclusion: MiRNA-17 and miRNA-222 can be considered as non-invasive biomarkers for detection of early lung carcinogenesis and metastasis in patients with NSCLC, hence providing a basis for the development of novel therapeutic approaches.

Circulating miRNA-21 and miRNA-23a Expression Signature as Potential Biomarkers for Early Detection of Non-Small-Cell Lung Cancer.

BACKGROUND AND AIM: Lung Cancer (LC) is a major cancer killer worldwide, and 5-yr survival is extremely poor (≤15%), accentuating the need for more effective diagnostic and therapeutic strategies. Studies have shown cell-free microRNAs (miRNAs) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study aimed to identify differentially-expressed two miRNAs in the plasma of Non-Small Cell Lung Cancer (NSCLC) patients that might be a clinically useful tool for lung cancer early detection. miRNA-21 is one of the most abundant oncomirs. miRNA-23a functions as an oncogene in several human cancers, however, its clinical value has not been investigated in NSCLC. MATERIALS AND METHODS: A case-control study was conducted in Assiut University Hospital, Egypt, from 2017 to 2018. Plasma samples were obtained from 45 NSCLC patients. The expression level of miR-21 and miRNA-23a was detected by qRT-PCR and compared to 40 healthy control subjects. The relation between both miRNAs and clinicopathological parameters was evaluated. RESULTS: The expression level of miR-21 and miRNA-23a was significantly up-regulated (36.9 ± 18.7 vs. 1.12 ± 0.84 and 24.7 ± 19.09 vs. 1.16 ± 0.45) in NSCLC compared to matched controls (P<0.0001each). There was a significant difference in the level of plasma miRNA-21 and miRNA- 23a expression between the different grades of the disease (P = 0.032 and P = 0.001, respectively). The plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with distant metastasis (n = 20) were significantly higher than those in the patients without metastasis (n = 25) (P<0.0001 each), the expression of miR-21 and miRNA-23a was significantly associated with tumor size (P = 0.001, P = 0.0001, respectively), but not significantly related to lymph node metastasis (P = 0.687 and 0.696, respectively). A positive correlation was observed between miRNA-21 and miRNA-23a (r = 0.784, P<0.01), There was no significant difference in the plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with different histopathological types. CONCLUSION: miR-21 and miR-23a might play an oncogenic role in LC and is a poor prognostic factor. Switching off miRNA-21 and miRNA-23a may improve the treatment of LC. Our results must be verified by large-scale prospective studies with standardized methodology.

Upper Egypt experience in bladder preservation using concurrent chemoradiotherapy.

OBJECTIVE: To share our experience in bladder preservation in Upper Egypt, Assiut and Sohag Universities, using different treatment protocols. In Sohag study patients with operable muscle invasive bladder cancer were included and underwent transurethral resection followed by radiochemotherapy (5- fluorouracil and Cisplatin) for bladder preservation. In Assiut study after maximum safe resection of bladder tumor, patients received combined chemo-radiotherapy, 60 Gy of fractionated radiotherapy over 6 weeks, with Cisplatin and Gemcitabine. RESULTS: In Sohag study the age of patients ranged from 35-72ys with Median 56 years, 24 patients were male (80%) and 6 patients were female (20%). In Assiut study the mean of age was 57.30 years, median 58.5 years with peak incidence in 7th decade (9 cases) then in 6th decade 7 cases (23.33%). Performance status was represented as following, 23 patients (76.6%) were scale 1 and seven patients (23.3%) were scale 2. In Assiut study, 90% of patients were disease free at the time of cystoscopic reevaluation. Of concern is that within 18 months of follow up in Assiut study, 7 of 27 (74%) complete responding patients have had local recurrence and 66.7% of all cases. The recurrence free survival in Sohag study at the median follow up (17 months) was 84% and at the end of follow up (30 months) was 70%. The overall survival at the median follow up was 95%, and at the end of follow up was 84%. The disease free survival in Assiut study was 66.7% and the overall Survival in Assiut study was 76.7. CONCLUSION: Three significant prognostic factors were detected for overall survival, performance status, tumor size and residual of tumor and two significant prognostic factors were detected for disease free survival, tumor size and residual of tumor in Assiut study. And it was nearly similar to that reported by Sohag study as they found the completeness of TUR and early stage of the tumor had the strongest impact in response to treatment.