Penetrance of <i>MYOC</i> gene mutation in primary open-angle glaucoma: A systematic review and meta-analysis

To investigate the penetrance of MYOC gene mutation in primary open-angle glaucoma (POAG) through systematic review and meta-analysis. To explore the factors affecting the penetrance of MYOC and provide evidence-based medical evidence for clinical work. We searched all studies that reported the penetrance of MYOC mutation in PubMed, Embase, Web of Science, and Chinese databases including Wanfang, CNKI (China National Knowledge Infrastructure), and CBM (China Bio-Med). Random effects meta-analysis was conducted to estimate the penetrance of MYOC mutation in POAG. Fifty-two studies were included in this analysis after screening. Meta-analysis of the penetrance of MYOC mutation showed that the penetrance of MYOC mutation in POAG was 60% (95% CI: 51.0% to 68.0%) and the penetrance of MYOC mutation in POAG and suspected POAG was 68% (95% CI: 60.0% to 75.0%). The penetrance of MYOC mutation increases with age. Among Caucasians, Asians, and Africans, the penetrance of MYOC mutation in POAG was 55%, 71%, 54%, respectively, and the penetrance of MYOC mutation in POAG and suspected POAG was 64%, 83%, and 57%, respectively. Besides, the penetrance of different MYOC mutation sites was significantly discrepant. The penetrance of MYOC mutation in POAG ranged from 10.3% to 100% depending on the mutation sites. Some MYOC mutation sites have a certain population specificity, which is only pathogenic in Caucasians or Asians. The penetrance of MYOC mutation in POAG showed significant differences due to different mutation sites. The penetrance increased with the accrescent of age. Ethnic difference was an important factor affecting the penetrance of MYOC mutation. Knowing the rules and influencing factors of the penetrance of MYOC mutations is significant for the assessment of the risk of POAG in carriers with the MYOC mutation.</p

Table1_Roles and Clinical Significances of ATF6, EMC6, and APAF1 in Prognosis of Pancreatic Cancer.DOCX

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients.Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to evaluate prognosis value of ATF6, EMC6, XBP1, CHOP, and APAF1 in PC. Clinical data from 69 PC patients were retrospectively analyzed. Immunohistochemistry, Western blotting, and qRT-PCR were used for the assessment of gene or protein expression. The cell counting kit-8 (CCK-8) and the Transwell invasion assays were, respectively, used for the assessment of the proliferative and invasive abilities of PC cells. The prognostic values of ATF6, XBP1, CHOP, EMC6, and APAF1 in PC patients were evaluated using Kaplan–Meier and Cox regression analyses.Results: XBP1 and CHOP expressions were not associated with PC recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). ATF6 upregulation and EMC6 and APAF1 downregulations significantly correlated with the poor RFS, OS, and DSS of PC patients. ATF6 promoted PC cell proliferation and invasion, while EMC6 and APAF1 inhibited these events.Conclusion: ATF6 upregulation and EMC6 and APAF1 downregulations may be valid indicators of poor prognosis of PC patients. Moreover, ATF6, EMC6, and APAF1 may constitute potential therapeutic targets in PC patients.</p