Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma

Zhang, Jie; Gu, Chaoyu; Song, Qisheng; Zhu, Mengqi; Xu, Yuqing; Xiao, Mingbing; Zheng, Wenjie

doi:10.1186/s13578-020-00488-y

Cited by 58 publications

(56 citation statements)

References 134 publications

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“…The tumor microenvironment (TME) is a sophisticated organizational structure that refers to the intracellular milieu produced by tumor cells and required for tumor cells to survive, including fibroblasts, tumor cells, inflammatory and immune cells and other types of cells around them, as well as intercellular stroma, extracellular matrix (ECM), microvessels and signaling biomolecules in nearby areas [ 9 ]. Tumor development and progression are affected by changes in the TME, which is produced by the dynamic interaction between malignant cells and normal cells.…”

Section: Introductionmentioning

confidence: 99%

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang

Zhu³

et al. 2021

Cancer Cell Int

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Methyltransferase-like 7B (METTL7B) is a member of the methyltransferase-like protein family that plays an important role in the development and progression of tumors. However, its prognostic value and the correlation of METTL7B expression and tumor immunity in some cancers remain unclear. By analyzing online data, we found that METTL7B is abnormally overexpressed in multiple human tumors and plays an important role in the overall survival (OS) of patients with 8 cancer types and disease-free survival (DFS) of patients with 5 cancer types. Remarkably, METTL7B expression was positively correlated with the OS and DFS of patients with lower-grade glioma (LGG). In addition, a positive correlation between METTL7B expression and immune cell infiltration in LGG was observed. Moreover, we identified a strong correlation between METTL7B expression and immune checkpoint gene expression in kidney chromophobe (KICH), LGG and pheochromocytoma and paraganglioma (PCPG). Furthermore, METTL7B was involved in the extracellular matrix (ECM) and immune-related pathways in LGGs. Finally, in vitro experiments showed that knockdown of METTL7B inhibited the growth, migration, invasion and the epithelial–mesenchymal transition (EMT) of LGG cells. METTL7B expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in LGG.

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Section: Introductionmentioning

confidence: 99%

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang

Zhu³

et al. 2021

Cancer Cell Int

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“…Although epithelial cell signaling in Helicobacter pylori infection and oocyte meiosis are not associated with HCC progression, evidence suggests that TLR is involved in modulating the previous pathways ( Smith et al, 2011 ; Gilbert, 2019 ). The tumor microenvironment including fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix plays a critical role in the initiation, growth, and dissemination of HCC ( Zhang et al, 2020 ). Here, we observed that high RS was characterized by a high immune score, immune checkpoint expression, and immune cell infiltration in HCC.…”

Section: Discussionmentioning

confidence: 99%

Development of a Toll-Like Receptor-Based Gene Signature That Can Predict Prognosis, Tumor Microenvironment, and Chemotherapy Response for Hepatocellular Carcinoma

Liu

et al. 2021

Front. Mol. Biosci.

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Objective: Emerging evidence highlights the implications of the toll-like receptor (TLR) signaling pathway in the pathogenesis and therapeutic regimens of hepatocellular carcinoma (HCC). Herein, a prognostic TLR-based gene signature was conducted for HCC.Methods: HCC-specific TLRs were screened in the TCGA cohort. A LASSO model was constructed based on prognosis-related HCC-specific TLRs. The predictive efficacy, sensitivity, and independency of this signature was then evaluated and externally verified in the ICGC, GSE14520, and GSE76427 cohorts. The associations between this signature and tumor microenvironment (stromal/immune score, immune checkpoint expression, and immune cell infiltrations) and chemotherapy response were assessed in HCC specimens. The expression of TLRs in this signature was verified in HCC and normal liver tissues by Western blot. Following si-MAP2K2 transfection, colony formation and apoptosis of Huh7 and HepG2 cells were examined.Results: Herein, we identified 60 HCC-specific TLRs. A TLR-based gene signature (MAP2K2, IRAK1, RAC1, TRAF3, MAP3K7, and SPP1) was conducted for HCC prognosis. High-risk patients exhibited undesirable outcomes. ROC curves confirmed the well prediction performance of this signature. Multivariate Cox regression analysis demonstrated that the signature was an independent prognostic indicator. Also, high-risk HCC was characterized by an increased immune score, immune checkpoint expression, and immune cell infiltration. Meanwhile, high-risk patients displayed higher sensitivity to gemcitabine and cisplatin. The dysregulation of TLRs in the signature was confirmed in HCC. MAP2K2 knockdown weakened colony formation and elevated apoptosis of Huh7 and HepG2 cells.Conclusion: Collectively, this TLR-based gene signature might assist clinicians to select personalized therapy programs for HCC patients.

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“…The main pathological type of NPC is squamous cell carcinoma, but cell cycle genes have been reported to affect the differentiation of squamous cells 25,26 . ECM-related genes play an indispensable role in the tumor microenvironment, and their potential as target genes and biomarkers has been described in many studies 27 . The susceptibility to NPC in the Chinese population is closely related to the interleukin (IL)-13 gene 28 , while IL-4 has been shown to affect the progression of NPC by affecting the signal transducer and activator of transcription (STAT) pathway 29 .…”

Section: Discussionmentioning

confidence: 99%

miRNAs Associated with Nasopharyngeal Carcinoma: New Prognostic Biomarkers and Therapeutic Targets

Zhu

et al. 2021

Preprint

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Background: Most of the studies included in this analysis highlighted miRNAsrole in the prognosis of nasopharyngeal carcinoma (NPC) patients. Our aim in this bioinformatics study was to synthesize relevant data associated with NPC to identify new prognostic markers. Methods: miRNA and mRNA data related to NPC were downloaded from the Gene Expression Omnibus (GEO) database. A variety of online analytical tools (starBase, TargetScanHuman7.2, Metascape, Cytoscape_v3.6.0, and GEPIA) were used to analyze the downloaded data to identify biomarkers with extremely high sensitivity and further research value. Results: Changes in the expression levels of 13 miRNAs played crucial roles in the overall survival of NPC patients (miR-375 was down-regulated, miR-96-5p, miR-155-5p, miR-320a, miR-378a-3p, miR-15b-5p, miR-21-5p, miR-25-3p, miR-93-5p, miR-493-3p, miR-493-5p, miR-494-3p, and let-7i-5p were up-regulated). Additionally, eight central genes (CDK1, CCNB1, CCNA2, TOP2A, AURKA, MAD2L1, CDC6, and CHEK1) were identified as target genes for further NPC therapy. Conclusions: Our findings further elucidate the underlying relationship between miRNAs and prognosis in NPC. The identified miRNAs are closely related to NPC prognosis and have extremely high research value for future medical treatment.

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Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma

Cited by 58 publications

References 134 publications

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Development of a Toll-Like Receptor-Based Gene Signature That Can Predict Prognosis, Tumor Microenvironment, and Chemotherapy Response for Hepatocellular Carcinoma

miRNAs Associated with Nasopharyngeal Carcinoma: New Prognostic Biomarkers and Therapeutic Targets

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