Background: Numerous studies reported RAS-association domain family 1 isoform A ( RASSF1A ) methylation might act as diagnostic biomarker for breast cancer (BC), this meta-analysis aimed to evaluate the value of RASSF1A methylation for diagnosing BC. Methods: Such databases as PubMed, Cochrane Library and Web of Science databases were searched for literatures until May 2019. A meta-analysis was performed utilizing STATA and Revman softwares. Furthermore, subgroup analysis was adopted to determine likely sources of heterogeneity. Results: Totally 19 literatures with 1849 patients and 1542 controls were included in this study. Sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic curve (AUC) of RASSF1A methylation for diagnosing BC was 0.49, 0.95, 19.0 and 0.83, respectively. The sensitivity (0.54 vs 0.43) , DOR (30.0 vs 10.0) and AUC (0.84 vs 0.81) of RASSF1A methylation in Caucasian were higher than other ethnicities. The sensitivity (0.64 vs 0.57), DOR (21.0 vs 14.0) and AUC (0.89 vs 0.86) of methylation-specific PCR (MSP) were superior to other methods (q-MSP, OS-MSP and MethyLight). The sensitivity, DOR and AUC of serum RASSF1A methylation vs RASSF1A methylation in other samples (tissue or plasma) were 0.55 vs 0.40, 22.0 vs 14.0 and 0.86 vs 0.74, respectively. Conclusions: RASSF1A methylation might be a potential diagnostic biomarker for BC. Considering its low sensitivity and high specificity, it should combine with others to upgrade the sensitivity. Besides, under such conditions as MSP detection, serum RASSF1A methylation and in Caucasian it shown more effective and suitable for diagnosing BC.

Background: SphK1 is a conserved lipid kinase, which can catalyze the formation of tumorpromoting factor sphingosine phosphate-1 (S1P). Objective: This study aimed to investigate the effect of SphK1 on the proliferation/migration of colon cancer cells and associated mechanisms. Methods: Transcription of the SphK1 gene in colon cancer cells was detected. Gene transcription of SphK1 was inhibited by transfecting with the si-SphK1 gene in colon cancer cells. Effects of SphK1 inhibition (si-SphK1) on cell migration/proliferation were detected using the transwell system and MTS. Gene transcription of SIP, S1PR1, S1PR2, S1PR3, and activation of JAK/STAT3 pathway were examined using RT-PCR and western blot assay. S1PR1 over-expressing plasmid was constructed and transfected into cells. Effects of S1PR1 overexpression on migration/proliferation of si-SphK1 transfected colon cancer cells and activation of JAK/STAT3 pathway were determined using RT-PCR and western blotting. Results: Gene transcription of SphK1 in SW480 and HT-29 colon cancer cells was significantly inhibited by transfection of the si-SphK1 gene. Transwell migration and MTS findings showed that si-SphK1 transfection (si- SphK1 group) could reduce migration quantity and cell viability of colon cancer cells compared to the negative control (NC) (p<0.0001). SphK1 inhibition (si-SphK1 group) significantly down-regulated S1PR1 and S1PR3 gene transcription in SW480 and HT-29 cells (p<0.0001) and decreased activation level of JAKSTAT3 signaling pathway compared to NC group (p<0.05). Over-expression of S1PR1 reversed inhibitory effects of si-SphK1 on migration/proliferation of SW480 and activation of JAK/Stat3. Conclusion: SphK1 promoted proliferation and migration of colon cancer cells through promoting JAK/STAT activation and up-regulating S1PR1 expression.