ABSTRACT
Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.
Subject(s)
Humans , Female , Ovarian Neoplasms/genetics , Cell Proliferation , Cytokines , Endoplasmic Reticulum Stress/geneticsABSTRACT
The data of a patient with autosomal dominant optic atrophy (ADOA) and chronic renal insufficiency caused by SSBP1 gene mutation in the Children′s Hospital Affiliated to Zhengzhou University in July 2021 was analyzed retrospectively.Literature was reviewed.The patient was a 10-year-old girl, who visited the hospital due to " growth retardation for the past 3 years and elevated serum creatinine (Scr) for the past 2 years" . On admission, the patient′s height was 130 cm (<10 th percentile of the same sex of healthy age) and her weight was 22 kg (<3 rd precentile of the same sex of healthy age). Lab examination showed that the level of blood urea nitrogen (BUN) was 16.3 mmol/L, Scr was 115.4 μmol/L, and the estimated glomerular filtration rate was 41 mL/(min·1.73 m 2). The patient was complicated with metabolic acidosis and mild anemia.Imaging findings showed small volume of both kidneys, increased background parenchymal enhancement, scattered spot-like hyperechoes and unclear boundary between the cortex and medulla.Additionally, the patient had a history of optic atrophy.Both the father and mother of the patient had no related phenotypes.The genetic test of the patient showed that c. 320G>A (p.R107Q) was a heterozygous missense mutation, which was spontaneous.A total of 5 English papers were retrieved.There were 8 kinds of SSBP1 gene mutations reported, including 7 heterozygous missense mutations [c.320G>A (p.Arg107Gln), c.119G>T (p.Gly40Val), c.331G>C (p.Glu111Gln), c.184A>G (p.Asn62Asp), c.113G>A (p.Arg38Gln), c.422G>A (p.Ser141Asn), c.79G>A (p.Glu27Lys)] and 1 homozygous mutation [c.394A>G (p.Ile132Val)]. Studies have established that almost all patients carrying SSBP1 mutations have manifestations of eye involvement, and that some patients are complicated with progressive deterioration of renal function, sensorineural deafness, growth retardation, and hypothyroidism.It suggests that SSBP1 gene mutation can cause ADOA.For patients with optic atrophy, whether they are complicated with hearing loss and growth retardation, renal morphology and renal function evaluation are recommended.Early genetic examination is helpful for diagnosis and treatment.
ABSTRACT
Objective To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor on peritoneal lymphangiogenesis and peritoneum function in uremic rat.Methods Uremic rats treated by peritoneal dialysis were intragastric administration celecoxib.Structures of peritoneum,peritoneal function,peritoneal lymphatic vessel density (LVD) were detected in every group.The mRNA of vascular endothelial growth factor-C (VEGF-C),lymphatic vessel endothelial hyluronan receptor-1 (LYVE-1) and COX-2 were tested by RT-PCR.The protein expressions of LYVE-1,VEGF-C,COX-2 were tested by western blot.Results With the extension of the duration of dialysis,the peritoneum thickness was increasing,inflammatory cell infiltrated obviously,uhrafiltration volume decreased significantly.But the celecoxib could increase uhrafiltration volume and reduce the glucose transport rate(P ＜0.05).Compared with the normal group,the levels of LVD,COX-2,VEGF-C,and LYVE-1 mRNA and protein were significantly up-regulated in uremic and dialysis groups (P ＜0.05).Compared with the uremic dialysis group,the levels of LVD,COX-2,VEGFC and LYVE-1 mRNA and protein were significantly down-regulated in the celecoxib group.There was a positive correlation between COX-2 and VEGF-C,LVD in protein levels,as well as VEGF-C and LVD (all P values ＜ 0.05).Conclusions Hyper glucose dialysis solution and uremic condition could up-regulate the expression of COX-2,VEGF-C,LYVE-1 in gene and protein level and stimulate lymphangiogenesis.COX-2 inhibitor could delay the change of peritoneal structures and function.COX-2 inhibitor could prevem the lymphangiogenesis in uremic rat treated by peritoneal dialysis,which might down-regulate the expression of VEGF-C by COX-2 depended manner.
ABSTRACT
Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats.Methods Forty-eight male SD rats were selected,and they were randomly divided into five groups:normal control group(n =8),sham operation group(n =8),uremia group(5/6 nephrectomy,n =8),PD group [4.25％ PD solution,2 weeks PD model(n =8) and 4 weeks PD model(n =8)],PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage,n =8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures,functions,peritoneal tissue capillary density (microvessel density,MVD) and COX-2,vascular endothelial growth factor (VEGF) expression level,and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study.Results With the conduct of the peritoneal dialysis,peritoneal thickness increased,the inflammatory cells infiltrated,peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P ＜ 0.05),the amount of glucose transport rate rised significantly (P ＜ 0.05),but the celecoxib could improve net ultrafiltration volume (P ＜ 0.05),and reduce the glucose transport rate (P ＜ 0.05).The peritoneal tissue MVD and COX-2,VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P ＜ 0.05),were significantly lower in PD + Celecoxib intervention group than that in uremia group (P ＜ 0.05).The correlation analysis showed that the level of COX-2 protein expression with MVD,VEGF protein expression was positively correlated (both P ＜ 0.05),the level of VEGF protein expression and MVD was positively correlated (P ＜ 0.05).Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised,and the capillaries production increased in peritoneal tissue.Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats.Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats,possibly through inhibition of COX-2 expression to reduce the production of VEGF.