Scientific Reports
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2015
·Vol. 5
·期 1
·1-11
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IF 5.578
Yang Ting,Xu Feifei,Fang Danjun,Chen Yun
The distinct roles of protein isoforms in cancer are becoming increasingly evident. FRα and FRβ, two major isoforms of the folate receptor family, generally have different cellular distribution and tissue specificity. However, the presence of FRβ in breast tumors, where FRα is normally expressed, complicates this situation. Prior to applying any FR isoform-based diagnosis and therapeutics, it is essential to monitor the expression profile of FR isoforms in a more accurate manner. An LC-MS/MS-based targeted proteomics assay was developed and validated in this study because of the lack of suitable methodology for the simultaneous and specific measurement of highly homologous isoforms occurring at low concentrations. FRα and FRβ monitoring was achieved by measuring their surrogate isoform-specific peptides. Five human breast cell lines, isolated macrophages and 60 matched pairs of breast tissue samples were subjected to the analysis. The results indicated that FRβ was overexpressed in tumor-associated macrophages (TAMs) but not epithelial cells, in addition to an enhanced level of FRα in breast cancer cells and tissue samples. Moreover, the levels of the FR isoforms were evaluated according to the histology, histopathological features and molecular subtypes of breast cancer. Several positive associations with PR/ER and HER2 status and metastasis were revealed.
研究领域:
癌症生物学
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蛋白质组学
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临床肿瘤学
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DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-18
·
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
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Shichao Zhang,Yijiang Liu,Yuhan Xie,Chenchun Ding,Renjie Zuo,Zhenzhen Guo,Shiyong Qi,Tingting Fu,Weibin Chen
Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein–protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.
研究领域:
癌症生物学
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分子生物学
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免疫学
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生物信息学
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基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Wu Min,Wang Tingting,Ji Nan,Lu Ting,Yuan Ran,Wu Lingxiang,Zhang Junxia,Li Mengyuan,Cao Penghui,Zhao Jiarui,Li Guanzhang,Li Jianyu,Li Yu,Tang Yujie,Gao Zhengliang,Wang Xiuxing,Cheng Wen,Ge Ming,Cui Gang,Li Rui,Wu Anhua,You Yongping,Zhang Wei,Wang Qianghu,Chen Jian
Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.
研究领域:
肿瘤学
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基因组学
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药理学
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神经科学
✓ 已验证
DOI
PubMed
高影响因子
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