Impact of Vitamin D on Expression of SIRT7 and CYP24A1 in Human Breast Cancer Cells

Objectives: Impact of vitamin D (1, 25 dihydroxy vitamin D3) (calcitriol) in the regulation of different genes has been investigated in different cancers including breast cancer (BC). Material and Methods: In the current study, we analyzed the expression levels of the CYP24A1 and SIRT7 genes and their relationship with patients’ clinical data in BC using polymerase chain reaction (PCR). Afterward, we tend to analyze the effect of vitamin D on the expression of these genes in cell lines (MCF7 and MDAMB231) to find the regulatory role of vitamin D in BC. Results: Our results showed that the CYP24A1 and SIRT7 were increased by vitamin D treatment and CYP24A1 levels were related to tumors stages (p = 0.03) and up-regulation of CYP24A1, SIRT7 had the distinguish potential for breast cancer detection based on their receiver operative characteristic (ROC) curve results (0.77, 0.84, respectively). Conclusion: In summary, CYP24A1, SIRT7 may be used as a possible diagnostic biomarker in BC treatment.

Plasma circN4BP2L2 is a promising novel diagnostic biomarker for epithelial ovarian cancer

Background Circular RNAs (circRNAs) are more stable than linear RNA molecules, which makes them promising diagnostic biomarkers for diseases. By circRNA-sequencing analysis, we previously found that circN4BP2L2 was significantly decreased in epithelial ovarian cancer (EOC) tissues, and was predictive of disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 in EOC. Methods Three hundred seventy-eight plasma samples were acquired prior to surgery. Samples were obtained from 126 EOC patients, 126 benign ovarian cyst patients, and 126 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). EOC cells were transfected with small interference RNAs (siRNAs) and cell proliferation, migration, invasion, cell cycle and cell apoptosis were performed to assess the effect of circN4BP2L2 in EOC. Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. Results Plasma circN4BP2L2 was significantly downregulated in EOC patients. Decreased circN4BP2L2 was significantly associated with advanced tumor stage, worse histological grade, lymph node metastasis and distant metastasis in EOC. CircN4BP2L2 inhibited tumor cell migration and invasion in vitro. CircN4BP2L2 could significantly separate EOC from benign (AUC = 0.82, P < 0.01) or normal (AUC = 0.90, P < 0.01) cohort. Early stage EOC vs benign (AUC = 0.81, P < 0.01) or normal (AUC = 0.90, P < 0.01) cohort could also be distinguished by circN4BP2L2. In discrimination between EOC cohort and benign or normal cohort, circN4BP2L2 performed equally well in both pre- and post-menopausal women. The combination of circN4BP2L2, CA125 and HE4 showed high sensitivity and specificity in detecting EOC cases. Conclusions Plasma circN4BP2L2 is significantly downregulated in EOC and might serve as a promising novel diagnostic biomarker for EOC patients, especially in early stage EOC cases. CircN4BP2L2 might act as an adjunct to CA125 and HE4 in detecting EOC. Further large-scale studies are warranted to verify our results.

Elevated Interleukin-6 Levels in the Circulation and Peritoneal Fluid of Patients with Ovarian Cancer as a Potential Diagnostic Biomarker: A Systematic Review and Meta-Analysis

Ovarian cancer (OC) is one of the most lethal cancers, largely due to a late diagnosis. This study aimed to provide a comprehensive meta-analysis on the diagnostic performance of IL6 in the blood and ascites separately for advanced and early-stage OC. We included 37 studies with 6948 participants detecting serum or plasma IL6. The plasma/serum IL6 mean level in the late-stage OC was 23.88 pg/mL (95% CI: 13.84–41.23), and the early-stage OC was 16.67 pg/mL (95% CI: 510.06–27.61), significantly higher than the healthy controls at 3.96 pg/mL (95% CI: 2.02–7.73), but not significantly higher than those found in the controls with benign growths in the ovary, which was 9.63 pg/mL (95% CI: 4.16–22.26). To evaluate IL6 in ascites as a diagnostic marker, we included 26 studies with 1590 participants. The mean level of ascitic IL6 in the late-stage OC was 3676.93 pg/mL (95% CI: 1891.7–7146.7), and the early-stage OC was 1519.21 pg/mL (95% CI: 604.6–3817.7), significantly higher than the benign controls at 247.33 pg/mL (95% CI: 96.2–636.0). There was no significant correlation between the levels of circulating and ascitic IL6. When pooling all OC stages for analysis, we found that serum/plasma IL6 provided 76.7% sensitivity (95% CI: 0.71–0.92) and 72% specificity (95% CI: 0.64–0.79). Ascitic IL6 provided higher sensitivity at 84% (95% CI: 0.710–0.919) and specificity at 74% (95% CI: 0.646–0.826). This study highlights the utility of ascitic IL6 for early detection of OC.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients

Background. Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). Methods. In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. Results. CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. Conclusions. CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.