Scientific Reports
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2024
·Vol. 14
·期 1
·1-12
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IF 3.8
Li Chao,Xiong Zhen,Han Jinxin,Nian Weiqi,Wang Zheng,Cai Kailin,Gao Jinbo,Wang Guobin,Tao Kaixiong,Cai Ming
Gastric cancer (GC) is one of the most common and deadliest cancers worldwide. Lipid homeostasis is essential for tumour development because lipid metabolism is one of the most important metabolic reprogramming pathways within tumours. Elucidating the mechanism of lipid homeostasis in GC might significantly improve treatment strategies and patient prognosis. GSE62254 was applied to construct a lipid homeostasis-related gene signature score (HGSscore) by multiple bioinformatic algorithms including weighted gene coexpression network analysis (WGCNA) and LASSO-Cox regression. A nomogram based on HGSscore and relevant clinical characteristics was constructed to predict the survival of patients with GC. TIMER and xCell were used to evaluate immune and stromal cell infiltration in the tumour microenvironment. Correlations between lipid homeostasis-related genes and chemotherapeutic efficacy were analysed in GSCAlite. RT‒qPCR and cell viability assays were applied to verify the findings in this study. HGSscore was constructed based on eighteen lipid homeostasis-related genes that were selected by WGCNA and LASSO-Cox regression. HGSscore was strongly associated with advanced TNM stage and showed satisfactory value in predicting GC prognosis in three independent cohorts. Furthermore, we found that HGSscore was associated with the tumour mutation burden (TMB) and immune/stromal cell infiltration, which are related to GC prognosis, indicating that lipid homeostasis impacts the formation of the tumour microenvironment (TME). With respect to the GSCAlite platform, PLOD2 and TGFB2 were shown to be positively related to chemotherapeutic resistance, while SLC10A7 was a favourable factor for chemotherapy efficacy. Cell viability assays showed that disrupted lipid homeostasis could attenuate GC cell viability. Moreover, RT‒qPCR revealed that lipid homeostasis could influence expression of specific genes. We identified a lipid homeostasis-related gene signature that correlated with survival, clinical characteristics, the TME, and chemotherapeutic efficacy in GC patients. This research provides a new perspective for improving prognosis and guiding individualized chemotherapy for patients with GC.
研究领域:
肿瘤学
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生物信息学
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分子生物学
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DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Weiliang Xiong,Wanli Peng,Yali Fu,Zixin Deng,Shuangjun Lin,Rubing Liang
Environmental estrogen contamination poses severe threat to wildlife and human. Biodegradation is an efficient strategy to remove the wide-spread natural estrogen, while strains suitable for hostile environments and fit for practical application are rare. In this work, Microbacterium hominis SJTG1 was isolated and identified with high degrading efficiency for 17β-estradiol (E2) and great environment fitness. It could degrade nearly 100% of 10 mg/L E2 in minimal medium in 6 days, and remove 93% of 1 mg/L E2 and 74% of 10 mg/L E2 in the simulated E2-polluted solid soil in 10 days. It maintained stable E2-degrading efficiency in various harsh conditions like non-neutral pH, high salinity , stress of heavy metals and surfactants. Genome mining and comparative genome analysis revealed that there are multiple genes potentially associated with steroid degradation in strain SJTG1. One 3β/17β-hydroxysteroid dehydrogenase HSD-G129 induced by E2 catalyzed the 3β/17β-dehydrogenation of E2 and other steroids efficiently. The transcription of hsd-G 129 gene was negatively regulated by the adjacent LysR-type transcriptional regulator LysR-G128, through specific binding to the conserved site. E2 can release this binding and initiate the degradation process. This work provides an efficient and adaptive E2-degrading strain and promotes the biodegrading mechanism study and actual remediation application.
研究领域:
环境科学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
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2025
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IF 3.3
Chen Dai,Rishun Su,Zhenzhen Zhao,Yangyang Guo,Wenbin Hou,Yulong He,Guangyao Liu,Songcheng Yin,Changhua Zhang
Background Gastric cancer (GC) is a very aggressive, with extreme heterogeneity and rapid growth, most frequently manifested histologically as stomach adenocarcinoma (STAD). Current evidence suggests that histone acetylation is critical for the origin and development of tumors. However, the significance of histone acetylation-related gene signatures for prognosis of STAD patients and mechanisms of histone acetylation in STAD therapy remains unclear. Methods We identified histone acetylation-related genes in STAD from TCGA and constructed eight-gene signatures by utilizing a univariate Cox regression model with the Least Absolute Shrinkage and Selection Operator (LASSO). In addition, a nomogram was plotted to predict the prognostic significance of the established risk model. We examined associations between our gene signature and somatic mutation, immune subtype, clinicopathological features, tumor microenvironment, immune cell infiltration and immune activity, immunotherapy prediction and drug sensitivity. Cell-based assays were performed to determine the relationship between Doublecortin Like Kinase 1 (DCLK1) and the proliferation, migration and oxaliplatin resistance of GC cells in vitro . Immunohistochemical experiments were used to explore the relationship between DCLK1 and clinicopathological parameters. Results A prognostic model composed of eight histone acetylation-related genes in STAD was developed. Based on median risk score, the STAD patients were equally assigned into two groups of high- and low-risk, where high-risk represented a less favorable prognosis than low-risk. The two groups showed significant differences with respect to somatic mutation, immune subtype, clinicopathological features, tumor microenvironment, immune cell infiltration and immune activity, immunotherapy prediction and drug sensitivity. The results generated during Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that Differentially Expressed Genes (DEGs) in the two groups were involved in cancer-related processes and pathways. Cell-based assays indicated that DCLK1 is a promoting factor in gastric cancer and can promote oxaliplatin resistance in gastric cancer cells. Increased DCLK1 expression was also associated with Borrmann’s Type, depth of invasion, lymph node metastasis, and TNM stage in GC patients. Conclusion A novel histone acetylation-related gene signature, which possesses potential value in predicting the prognosis and immunotherapy effectiveness regarding STAD patients, was developed. This signature may serve as a reliable biomarker for prognosis of STAD and promote the identification of novel treatment targets for STAD. Furthermore, DCLK1 exhibited oncogenic roles and may be a new target for STAD therapy.
研究领域:
肿瘤学
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分子生物学
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免疫治疗
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生物信息学
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癌症基因组学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-15
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IF 3.8
Ding Yangyang,Huang Keke,Sun Cheng,Liu Zelin,Zhu Jinli,Jiao Xunyi,Liao Ya,Feng Xiangjiang,Guo Jingjing,Zhu Chunhua,Zhai Zhimin,Xiong Shudao
Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL.
研究领域:
肿瘤学
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分子生物学
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免疫学
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癌症治疗
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基因组学
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DOI
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-18
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IF 3.9
Su Rishun,Chen Jia,Dai Chen,Yin Songcheng,Chen Haoming,Sun Xuezeng,Fang Zhaoxin,Zhang Changhua,Chen Jingyao,Gu Liang
G2/M checkpoint and P53 pathway are essential in regulating the cell cycle and proliferation of cells, which is related to the progress of tumors. Here, we carried out an integrative analysis of the prognostic genes of these pathways in gastric cancer (GC) and thus developed a molecular subtype. We identified prognostic differential expression genes (PDEGs) of G2/M checkpoint and P53 pathways between normal and tumor tissue in TCGA-STAD and developed a molecular subtype based on PDEGs. Meanwhile, the clinical significance of the molecular subtype was further explored. In addition, a comprehensive model and nomogram based on PDEGs score were constructed and validated by GSE26901 and GSE13861. Gastric cancer cell lines and patients’ specimens were used to validate the expression of selected genes.19 PDEGs were identified from these pathways in TCGA-STAD. Ulteriorly, a PDEGs score model consisting of 4 genes (PVT1, F2R, INCENP, IRAK1) was generated to classify patients into high- and low- PDEGs score subgroups. Patients in low PDEGs score groups had a better prognosis and a higher tumor mutational burden and may be more sensitive to chemotherapy and immunotherapy. Notably, the combination of PDEGs score and clinical features showed a pleasing survival prediction ability. In the GSE13861 cohort, the PDEGs score and its derivative model were confirmed with significant predictive effects in overall survival. Furthermore, these genes were significantly upregulated in both GC cell lines and tumor tissues and F2R was the hub gene resulting in poor survival. This paper has provided a distinct insight for tumor classification predicting prognosis more accurately and having the potential to instruct the use of chemotherapy and immunotherapy for patients with GC.
研究领域:
癌症研究
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分子生物学
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生物信息学
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基因组学
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肿瘤学
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计算生物学
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医学遗传学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-22
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IF 3.9
Bai Guannan,Zhao Shaobo,Chen Lushan,Zhao Manli,Chen Wenhao
Osteosarcoma (OS) is the most common bone malignancy in children and adolescents. The 5-year survival rate is only approximately 20% in patients with metastatic and recurrent OS. There is an urgent need to explore novel therapeutic targets to improve the survivorship of OS patients. It has been reported that dysfunction of programmed cell death (PCD) plays an essential role in tumor malignancy. In this study, differentially expressed PCD genes (PCD-DEGs) in OS were identified. Functional enrichment and somatic mutation analysis were performed. Then we established a novel indicator, the cell death index (CDI), to predict therapeutic interventions, immunity responses, and prognosis concerning OS. The expression of PCD genes in osteosarcoma and normal tissues was determined by immunohistochemistry assays. A total of 265 PCD-DEGs were identified in OS, with 141 genes upregulated and 124 genes downregulated. After functional enrichment and somatic mutation analysis, a final PCD-related gene signature, involving the expression levels of CLTCL1, FADS2, and PLEKHF1, demonstrated significant predictive value. A nomogram including clinical characteristics and CDI was developed, which was verified to perform well. Further investigation showed CDI was strongly correlated with immunomodulators, tumor microenvironment, and drug sensitivity in OS. Immunohistochemistry assays illustrated that FADS2, CLTCL1, and PLEKHF1 were suppressed in OS tissues. Further experiments demonstrated that FADS2 inhibits migration and invasion of osteosarcoma cells, while FADS2 induces ferroptosis collaborating with Erastin in osteosarcoma cells. In conclusion, the PCD-related gene signature proposed in this study is a practical prognostic predictor for OS patients, which can make a notable difference in the assessment of clinical outcomes.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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遗传学
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病理学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2023
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IF 10
Xiaofen Wang,Menglu Jiao,Fangzhen Tian,Xuan Lu,Huihuang Xiong,Fan Liu,Yiqun Wan,Xiaodong Zhang,Hao Wan
Ulcerative colitis (UC), a refractory disease, has become a global problem. Herein, a biomimetic nanoplatform (AU-LIP-CM) comprising Au cluster enzymes (AU)-loaded liposomes (AU-LIP) camouflaged with the fusion membrane (CM) consisting of neutrophil (NC) and red blood cell (RBC) membrane was designed for the treatment of UC. Briefly, revealed by second near-infrared (NIR-II) imaging through collection of fluorescence emitting > 1200 nm from AU, the improved inflammatory targeting behavior contributed by CM cloaking, which inherited abilities of inflammatory targeting and immune escape from NC and RBC, respectively, promoted specific accumulation of AU within inflammatory intestines with up to ∼11.5 times higher than that of bare AU. Afterwards, AU possessing superoxide dismutase- and catalase-like activities realized high-efficiency scavenging of reactive oxygen species (ROS), leading to repair of intestinal barriers, regulation of the immune system, and modulation of gut microbiota, which surpassed first-line UC drug. In addition, study of underlying therapeutic mechanism demonstrated the treatment with AU-LIP-CM could alter the gene signature associated with response to ROS for UC mice to a profile similar to that of healthy mice, deciphering related signal pathways. The strategy developed here provided insights of learning from properties of natural bio-substances to empower biomimetic nanoplatform to confront diseases. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
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生物医学工程
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药学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
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