Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(E...Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.展开更多
Cytochrome P450 （CYP） superfamily is one of the membership largest and function most diverse protein superfamily recogniozed among living beings. Members of this superfamily were further assigned to different famili...Cytochrome P450 （CYP） superfamily is one of the membership largest and function most diverse protein superfamily recogniozed among living beings. Members of this superfamily were further assigned to different families and subfamilies based on their amino acid similarities. According to their phylogenetic relationships, the CYP genes which likely diverged from common ancestor gene and may share common functions were grouped into one clan. Widely distributing scallops are a group of the most conspicuous bivalve; however the studies on their CYP is acarce. In this study, we searched the genome and expressed sequence tags of Zhikong scallop （Chlamysfarreri） for CYP genes. In total, 88 non-redundant CIfP were identified, which were homed in 13 CYPs gene families. Phylogenetic analysis divided these genes into 4 CYP clans. As in deuterostomes, Clan 2 was the largest, which contained 33 genes belonging to CYP1, CYP2, CYP17 and CYP356 families. Clan 3 contgained 19 genes belonging to CYP3, CYP5 and CYP30 families. Clan 4 contained 23 genes, all belonging to CYP4 family. The mitochondrial CYP clan contained 9 genes belonging to CYPIO and CYP24 families. In comparison, protostomes （C. farreri, D. pluex, D. melanogaster） contained more CYP genes than deuterostomes （S. purpuratus and vertebrates） in Clan 2 but less genes in Clan 3 and Clan 4. Our findings will aid to deciphering CYP function and evolution in scallops and bivalves.展开更多
基金Natural Science Foundation of Liaoning Province(2022-MS-083)Application Basic Research Plan of Liaoning Province(2023JH2/101300084).
文摘Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.
基金supported by National Natural Science Foundation of China (30972239)National High-Tech R&D Program (863 Program, 2012AA092204, 2012AA-10A401 and 2012AA10A402)+2 种基金Doctoral Fund of Ministry of Education of China (20100132110014)Earmarked Fund for Modern Agro-industry Technology Research System, Natural Science Foundation of Shandong Province (ZR2009DM019)Seed Improvement Project of Shandong Province
文摘Cytochrome P450 （CYP） superfamily is one of the membership largest and function most diverse protein superfamily recogniozed among living beings. Members of this superfamily were further assigned to different families and subfamilies based on their amino acid similarities. According to their phylogenetic relationships, the CYP genes which likely diverged from common ancestor gene and may share common functions were grouped into one clan. Widely distributing scallops are a group of the most conspicuous bivalve; however the studies on their CYP is acarce. In this study, we searched the genome and expressed sequence tags of Zhikong scallop （Chlamysfarreri） for CYP genes. In total, 88 non-redundant CIfP were identified, which were homed in 13 CYPs gene families. Phylogenetic analysis divided these genes into 4 CYP clans. As in deuterostomes, Clan 2 was the largest, which contained 33 genes belonging to CYP1, CYP2, CYP17 and CYP356 families. Clan 3 contgained 19 genes belonging to CYP3, CYP5 and CYP30 families. Clan 4 contained 23 genes, all belonging to CYP4 family. The mitochondrial CYP clan contained 9 genes belonging to CYPIO and CYP24 families. In comparison, protostomes （C. farreri, D. pluex, D. melanogaster） contained more CYP genes than deuterostomes （S. purpuratus and vertebrates） in Clan 2 but less genes in Clan 3 and Clan 4. Our findings will aid to deciphering CYP function and evolution in scallops and bivalves.
