iScience
·
2024
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IF 4.6
Wei Yao,Yihui Wang,Xin Zhang,Yuhe Lin
Pancreatic cancer (PC) is one of the most lethal malignancies and new therapeutic strategies are urgently needed. β1,3-N-acetylglucosaminyltransferase V (B3GNT5) may be a potential option for cancer treatment, but its role in PC remains unknown. In this study, we first demonstrated through bioinformatics analysis that B3GNT5 was high expression in PC and predicted poor prognosis. We further constructed B3GNT5 overexpression or knockdown cell lines by employing lentivirus packaging techniques and confirmed that B3GNT5 could promote tumor cell viability and autonomous growth using cultured cells and vivo xenograft models. In addition, we found that knockdown of B3GNT5 in PC cells inhibited cell migration, invasion, and angiogenesis, as well as stemness of cancer stem cells and enhanced chemotherapy sensitivity to gemcitabine. Mechanistically, overexpression of the transcription factor STAT5B in PC cells enhanced the transcriptional activity of the B3GNT5 promoter. Our work confirmed a tumor-promotive role of B3GNT5 in PC pathogenesis.
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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产品关联
DOI
PubMed
高影响因子
Portal Hypertension & Cirrhosis
·
2024
·Vol. 3
·期 2
·86-95
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IF 0
Kaibo Yang,Kunjin Wu,Zitong Lei,Tong Liu,Xing Zhang,Jing Li,Kun Yang,Qiuting Peng,Ting Lin,Chang Liu,Kai Qu
Aim Tumor budding (TB) has excellent prognostic value in many solid tumors, but there is little research on it in hepatocellular carcinoma (HCC). This study assessed the prognostic value of TB in patients with HCC who received hepatectomy. Methods This retrospective study included 210 patients with HCC who received curative hepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University, between 2016 and 2018. TB was evaluated on hematoxylin- and eosin-stained slides according to the criteria established by the 2016 International Tumor Budding Consensus Conference. t -tests, Chi-squared tests, and rank-sum tests were used to correlate the extent of TB with clinicopathological parameters. Prognostic analysis was performed using Cox regression models and the Kaplan–Meier method. Results The positive detection rate of TB was 45.2% (95/210) in 210 patients with HCC. Patients positive for TB always exhibit lower tumor differentiation, higher hepatitis B virus DNA levels, and more severe liver fibrosis. Multivariate Cox analysis identified TB (hazard ratio [HR]: 2.232, 95% confidence interval [CI]: 1.479–3.368, p < 0.001) as an independent prognostic factor for patients' recurrence-free survival (RFS), similar to tumor size (HR: 1.070, 95% CI: 1.070–1.142, p = 0.042) and satellite nodule (HR: 2.266, 95% CI: 1.298–3.956, p = 0.004). Kaplan–Meier analysis also demonstrated that TB-positive patients had a significantly worse RFS. Interestingly, subgroup analysis revealed that among HCC patients with negative microvascular invasion (MVI), TB was also strongly associated with RFS (HR: 3.206, 95% CI: 1.667–6.168, p < 0.001). These findings suggest that TB may serve as a supplemental prognostic biomarker for HCC-negative MVI. Conclusions TB is an adverse prognostic biomarker for HCC, particularly in patients negative for MVI. TB evaluation should be considered in the postoperative pathological examination of HCC in clinical practice. Graphical This study assessed tumor budding (TB) in hepatocellular carcinoma patients. TB refers to the detachment of tumor cells from the primary tumor mass, infiltrating the adjacent matrix and forming separate clusters. It may represent two distinct pathological features compared to microvascular invasion, which involves the invasion of tumor cells into microvessels. ECM: extracellular matrix. Key points Significant findings of the study This single-center study found that tumor budding (TB) positivity was significantly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). What this study adds TB could serve as a potential supplemental prognostic biomarker for HCC with negative microvascular invasion.
研究领域:
病理学
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肿瘤学
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外科学
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DOI
Frontiers in Oncology
·
2025
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IF 3.3
Shuming Chen,Xiaoxi Han,Yangyang Lu,Shasha Wang,Yuanyuan Fang,Chuanyu Leng,Xueying Sun,Xin Li,Wensheng Qiu,Weiwei Qi
Background The process of human aging is accompanied by an increased susceptibility to various cancers, including gastric cancer. This heightened susceptibility is linked to the shared molecular characteristics between aging and tumorigenesis. Autophagy is considered a critical mediator connecting aging and cancer, exerting a dynamic regulatory effect in conjunction with cellular senescence during tumor progression. In this study, a combined analysis of autophagy- and senescence-related genes was employed to comprehensively capture tumor heterogeneity. Methods The gene expression profiles and clinical data for GC samples were acquired from TCGA and GEO databases. Differentially expressed autophagy- and senescence-related genes (DEASRGs) were identified between tumor and normal tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to provide insights into biological significance. A prognostic signature was established using univariate Cox and LASSO regression analyses. Furthermore, consensus clustering analyses and nomograms were employed for survival prediction. TME and drug sensitivity analyses were conducted to compare differences between the groups. To predict immunotherapy efficacy, the correlations between risk score and immune checkpoints, MSI, TMB, and TIDE scores were investigated. Results A fourteen-gene prognostic signature with superior accuracy was constructed. GC patients were stratified into three distinct clusters, each exhibiting significant variations in their prognosis and immune microenvironments. Drug sensitivity analysis revealed that the low-risk group demonstrated greater responsiveness to several commonly used chemotherapeutic agents for gastric cancer, including oxaliplatin. TME analysis further indicated that the high-risk group exhibited increased immune cell infiltration, upregulated expression of ICs, and a higher stromal score, suggesting a greater capacity for immune evasion. In contrast, the low-risk group was characterized by a higher proportion of microsatellite instability-high (MSI-H) cases, an elevated TIDE score, and a greater TMB, indicating a higher likelihood of benefiting from immunotherapy. In addition, Single-cell sequencing demonstrated that TXNIP was expressed in epithelial cells. Cellular experiments preliminarily verified that TXNIP could promote the proliferation and migration of gastric cancer cells. Conclusion This study presents a robust predictive model for GC prognosis using autophagy- and senescence-related genes, demonstrating its ability to predict immune infiltration, immunotherapy effectiveness, and guide personalized treatment.
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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产品关联
DOI
PubMed
高影响因子
Nature Machine Intelligence
·
2021
·Vol. 3
·期 3
·199-217
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IF 15.508
Roberts Michael,Driggs Derek,Thorpe Matthew,Gilbey Julian,Yeung Michael,Ursprung Stephan,Aviles-Rivero Angelica I.,Etmann Christian,McCague Cathal,Beer Lucian,Weir-McCall Jonathan R.,Teng Zhongzhao,Gkrania-Klotsas Effrossyni,Rudd James H. F.,Sala Evis,Schönlieb Carola-Bibiane
Machine learning methods offer great promise for fast and accurate detection and prognostication of coronavirus disease 2019 (COVID-19) from standard-of-care chest radiographs (CXR) and chest computed tomography (CT) images. Many articles have been published in 2020 describing new machine learning-based models for both of these tasks, but it is unclear which are of potential clinical utility. In this systematic review, we consider all published papers and preprints, for the period from 1 January 2020 to 3 October 2020, which describe new machine learning models for the diagnosis or prognosis of COVID-19 from CXR or CT images. All manuscripts uploaded to bioRxiv, medRxiv and arXiv along with all entries in EMBASE and MEDLINE in this timeframe are considered. Our search identified 2,212 studies, of which 415 were included after initial screening and, after quality screening, 62 studies were included in this systematic review. Our review finds that none of the models identified are of potential clinical use due to methodological flaws and/or underlying biases. This is a major weakness, given the urgency with which validated COVID-19 models are needed. To address this, we give many recommendations which, if followed, will solve these issues and lead to higher-quality model development and well-documented manuscripts.
研究领域:
医学影像学
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人工智能
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流行病学
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DOI
高影响因子
Frontiers in Oncology
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2025
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IF 3.3
Xiaocui Zhong,Mamona Bilal,Yanqiu Zhou,Xiaojia Yang,Zuchao Qin,Qibing Li,Yang Yang,Ting-Li Han,Min Li
Introduction Aberrant fatty acid (FA) metabolism is increasingly recognized as a significant factor in ovarian cancer (OC) progression, although the comprehensive metabolic alterations across different body tissues remain unclear. Methods In this study, sixteen OC patients and twenty-nine non-cancer (NC) patients were recruited for metabolic profiling using a global and targeted metabolomic strategy based on a gas chromatography-hydrogen flame ionization detector (GC-FID). The patient survival was followed up to 3 years, and PFS was calculated. Results Our findings revealed distinct metabolite profiles that differentiate OC from NC groups across all sample types. We found seven, nine, and thirteen significant metabolites in subcutaneous fat, plasma, and ovarian tissue respectively. In particular, docosahexaenoic acid (DHA) and arachidonic acid (AA) levels were notably elevated in all sample types of OC patients. Furthermore, receiver operating characteristic (ROC) analysis highlight that three plasma FA showed the best specificity and sensitivity in differentiating the OC group from the NC group (Area Under The Curve, AUC > 0.89), including caprylic acid, myristoleic acid, and tetracosaenoic acid. Most of the significant FA in subcutaneous fat and ovarian tissue showed a high risk of OC. However, caprylic acid and tetracosanoic acid were identified as protective factors in the plasma sample. We also found that high levels of linoelaidic acid in subcutaneous fat and palmitelaidic acid in ovarian tissue were associated with poor prognosis. Pathway analysis indicated upregulation of fatty acid synthesis, inflammatory signaling, and ferroptosis pathways in OC patients. Discussion This study reveals a coordinated reprogramming of FA metabolism across multiple biospecimens in OC patients. Our results suggest that specific fatty acids may contribute to OC progression through dysregulation of fatty acid synthesis, inflammatory signaling, and ferroptosis. These findings offer mechanistic insights into OC progression and highlighting potential biomarkers and targeted therapeutic interventions.
研究领域:
肿瘤学
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代谢组学
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生物化学
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DOI
PubMed
高影响因子
Cancer Biomarkers
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2018
·Vol. 23
·期 4
·603-613
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IF 2.392
Liu Zhi-Biao,Tang Chen,Jin Xin,Liu Shou-Hou,Pi Wen
BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) has been shown to be a long noncoding RNA (lncRNA) that facilitates the progression of a number of malignancies. However, the expression pattern and biological function of SNHG12 in nasopharyngeal carcinoma (NPC) have not been investigated. OBJECTIVE: The aim of our study is to investigate the expression, clinical significance and function of SNHG12 in NPC. METHODS: RT-PCR was used to detect the expression of SNHG12 in NPC cell lines and primary tumor tissues. The correlation of SNHG12 with clinicopathological features and patient prognosis was analyzed. The biologic functions of SNHG12 in NPC were explored by MTT assay, colony formation assay, wound healing assays, transwell assay and flow cytometric analysis in vitro. The expression of EMT markers and Notch signal pathway markers were determined by western blotting. RESULTS: The expression levels of SNHG12 were up-regulated in both NPC tissues and cell lines. High SNHG12 expression was significantly associated with clinical stage, grade and poor prognosis. Multivariate analysis demonstrated that high lncRNA SNHG12 expression was an independent poor prognostic factor for NPC patients. Functionally, knockdown of SNHG12 suppressed NPC cells proliferation, migration and invasion. Mechanistic investigations showed that knockdown of SNHG12 suppressed the activation of EMT and Notch-1 signal pathway. CONCLUSIONS: Our data suggest that SNHG12 promotes the progression of NPC and is a potential therapeutic target for NPC intervention.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2022
·Vol. 12
·期 1
·1-13
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IF 4.996
Zhou Bin,Sha Shanshan,Tao Juan,Li Jun,Shen Chen,Zhu Jinjin,Tan Lulu,Dong Liyun,Huang Changzheng
Cutaneous melanoma (CM, hereafter referred to as melanoma) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in melanoma has not been fully elucidated. In this study, we examined the relationship between pyroptosis and the prognosis of melanoma through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with melanoma prognosis. A higher pyroptosis score was associated with a more favorable overall survival. We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively evaluate the prognosis of melanoma. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4 + T cells, CD8 + T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of melanoma to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified solute carrier family 31 member 2 ( SLC31A2 ) and collagen type 4 alpha 5 chain ( COL4A5 ) as being associated with resistance to most of these drugs. In conclusion, this PGS is an effective and novelty prognostic indicator in melanoma, and also has an association with the melanoma immune microenvironment and melanoma treatment decision-making.
研究领域:
肿瘤学
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生物信息学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-12
·
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
Metabolites
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2025
·Vol. 15
·期 4
·228
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IF 3.7
Zhuo-Min Zhu,Huan-Yu Liu,Na An,An-Ling Li,Jia Li,Sai-Jun Wang,Gui Yang,Yong-Wei Duan,Ying Yang,Mei Zhang,Quan-Fei Zhu,Song-Mei Liu,Yu-Qi Feng
Background/Objectives:Severe fever with thrombocytopenia syndrome (SFTS) is a viral infection primarily found in Asia, with a case fatality rate of about 10%. Despite its increasing prevalence, the underlying pathogenic mechanisms remain poorly understood, limiting the development of effective therapeutic interventions.Methods:We employed an untargeted metabolomics approach using liquid chromatography–mass spectrometry (LC-MS) to analyze serum samples from 78 SFTS patients during the acute phase of their illness. Differential metabolic features between survival and fatal cases were identified through multivariate statistical analysis. Furthermore, we constructed a metabolic prognostic model based on these biomarkers to predict disease severity.Results:Significant alterations were observed in four key metabolic pathways: sphingolipid metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, primary bile acid biosynthesis, and phenylalanine metabolism. Elevated levels of phenyllactic acid and isocitric acid were strongly associated with adverse outcomes and demonstrated high discriminatory power in distinguishing fatal cases from survivors. The metabolic prognostic model incorporating these biomarkers achieved a sensitivity of 75% and a specificity of 90% in predicting disease severity.Conclusions:Our findings highlight the pivotal role of metabolic dysregulation in the pathogenesis of SFTS and suggest that targeting specific metabolic pathways could open new avenues for therapeutic development. The identification of prognostic biomarkers provides a valuable tool for early risk stratification and timely clinical intervention, potentially improving patient outcomes.
研究领域:
传染病学
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代谢组学
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病毒学
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产品关联
DOI
PubMed
高影响因子
DNA AND CELL BIOLOGY
·
2022
·Vol. 41
·期 4
·424-436
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IF 3.55
Feng Chi,Fang Qiu,Xiaoming Jin,Long Chen,Guijin He,Sijia Han
Breast cancer (BC) is one of the most frequently occurring malignant tumors in female adults. The long intergenic nonprotein coding RNA 00982 (LINC00982) has been regarded as a cancer suppressor in several human cancers. However, the function and the underlying mechanisms of LINC00982 have not been studied in BC. The present study found that LINC00982 was significantly downregulated in BC tumor tissues, and the low LINC00982 level predicts a poor prognosis of BC. Through the overexpression and suppression of LINC00982 in two BC cell lines, we found that LINC00982 could inhibit cell proliferation, migration, and invasion by suppressing the activity of the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF-κB) signal pathway. Furthermore, luciferase reporter assay has been used to verify that LINC00982 functions as a molecular sponge for miR-765, which could target DPF3. The relative expression of miR-765 decreased with LINC00982 overexpressing, and DPF3 increased at the same time.In addition, the suppression of cell malignant phenotype caused by overexpression of LINC00982 can be reversed by inhibition of DPF3. To verify the function of LINC00982 in vivo, the BC cells were implanted in nude mice and the results suggested the tumor growth and malignant phenotype were suppressed by LINC00982. In this study, we prove that LINC00982 regulates the growth and development of BC through STAT3/NF-κB signal pathway, mediated by the miR-765/DPF3 axis. LINC00982 may function as a target molecule to take part in the prognosis and therapy of BC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR PROBES
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2025
·
IF 3
Xin Song,Sihao Chen,Junning Cheng,Haiyu Li,Ruixin Wu,Min Yan,Min Wang,Jie Li,Aishun Jin,Wang Wang
Purpose Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS. Methods The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells. Result CD8 + T cells, activated memory CD4 + T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes CCL5 , CXCL9 , CXCL13 , and HTRA1 , exhibited positive correlation with the infiltration of both CD8 + T cells and CD4 + T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics. Conclusion CCL5 , CXCL9 , CXCL13, and HTRA1 were OS hub genes positively correlate with CD8 + T cell and CD4 + T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.
研究领域:
肿瘤学
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免疫学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2022
·
IF 4.145
Wuguang Liu,Xiaolong Liu,Ying Liu,Ting Ling,Di Chen,Wuxiyar Otkur,Hailong Zhao,Ming Ma,Kexin Ma,Bing Dong,Zexuan Yang,Hai-long Piao,Rui Liang,Chengyong Dong
PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC. In HCC cells, overexpressing PLIN2 promoted cell proliferation , PLIN2-deficiency inhibited cell vitality. Mechanistically, silencing of PLIN2 expression downregulated hypoxia inducible factor 1-α (HIF1α) expression and this downregulation in turn inhibited the targeting genes of HIF1α. Furthermore, we found that PLIN2 stabilized and retarded the degradation of the HIF1α through autophagy-lysosomal pathway by inhibiting AMPK/ULK1. Collectively, we clarified the carcinogenic role of PLIN2 in HCC and suggested a prognostic biomarker for diagnosis and clinical therapy in the future.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）