Turning up a new pattern: Identification of cancer-associated fibroblast-related clusters in TNBC

Xie, Jun; Zheng, Shaoquan; Zou, Yutian; Tang, Yuhui; Tian, Wenwen; Wong, Chau‐Wei; Wu, Song; Ou, Xueqi; Zhao, W.; Cai, Manbo; Xie, Xiaoming

doi:10.3389/fimmu.2022.1022147

Cited by 35 publications

(24 citation statements)

References 44 publications

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“… 77 Besides, we also reported a novel CAFs‐related pattern in TNBC. 78 Indeed, in the pan‐cancer cohort analyses of this study, CAFs correlated with poor OS in most cancers. The result remained constant regardless of whether CAFs infiltration was estimated using the EPIC algorithms or the clustering method.…”

Section: Discussionmentioning

confidence: 69%

Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

Zheng

Liang

Tang

et al. 2023

Clinical & Translational Med

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Introduction Cancer‐associated fibroblasts (CAFs) are correlated with the immunotherapy response. However, the culprits that link CAFs to immunotherapy resistance are still rarely investigated in real‐world studies. Objectives This study aims to systematically assess the landscape of fibroblasts in cancer patients by combining single‐cell and bulk profiling data from pan‐cancer cohorts. We further sought to decipher the expression, survival predictive value and association with immunotherapy response of biglycan (BGN), a proteoglycan in the extracellular matrix, in multiple cohorts. Methods Pan‐cancer tumor bulks and 27 single‐cell RNA sequencing cohorts were enrolled to investigate the correlations and crosstalk between CAFs and tumor or immune cells. Specific secreting factors of CAFs were then identified by expression profiling at tissue microdissection, isolated primary fibroblasts and single‐cell level. The role of BGN was further dissected in additional three bulk and five single‐cell profiling datasets from immunotherapy cohorts and validated in real‐world patients who have received PD‐1 blockade using immunohistochemistry and immunofluorescence. Results CAFs were closely correlated with immune components. Frequent crosstalk between CAFs and other cells was revealed by the CellChat analysis. Single‐cell regulatory network inference and clustering identified common and distinct regulators for CAFs across cancers. The BGN was determined to be a specific secreting factor of CAFs. The BGN served as an unfavourable indicator for overall survival and immunotherapy response. In the real‐world immunotherapy cohort, patients with high BGN levels presented a higher proportion of poor response compared with those with low BGN (46.7% vs. 11.8%) and a lower level of infiltrating CD8+ T cells was also observed. Conclusions We highlighted the importance of CAFs in the tumor microenvironment and revealed that the BGN, which is mainly derived from CAFs, may be applicable in clinical practice and serve as a therapeutic target in immunotherapy resistance.

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Section: Discussionmentioning

confidence: 69%

Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

Zheng

Liang

Tang

et al. 2023

Clinical & Translational Med

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“…Once successful, it will herald the possibility of g_ Fusobacterium DNA as a prognostic biomarker in OSCC. This is similar to identifying markers of cell death to predict the clinical treatment of tumors ( Zou et al, 2019 ), such as breast cancer ( Huang et al, 2019 ; Xie et al, 2019 ). In addition, our population-based statistics may provide insights to develop strategies to prevent and treat oral cancer by targeting the oral microbiota for future studies.…”

Section: Discussionmentioning

confidence: 90%

The significant clinical correlation of the intratumor oral microbiome in oral squamous cell carcinoma based on tissue-derived sequencing

Wen

et al. 2023

Front. Physiol.

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Background: The microbiota is a critical component of the complex human microenvironment, impacting various physiological processes and disease development via the microbe–host interaction. In particular, the oral microbiota profoundly affects tumor development and progression. There is increasing evidence that oral microbiota is associated with the development of oral cancer, especially oral squamous cell carcinoma (OSCC).Methods: We comprehensively analyzed the oral microbiota in 133 OSCC samples worldwide. Subsequently, we evaluated the microbial compositions between OSCC patients and healthy people and their correlation with clinical parameters. The value of the oral microbiota as a diagnostic and prognostic biomarker was also determined.Results: This study found differences in critical oral microbiota between OSCC and normal controls. The most notable differences are present in p_Firmicutes, p_Actinobacteria, c_Fusobacteriia, o_Fusobacteriales, f_Fusobacteriaceae, and g_Fusobacterium. All six-level oral microorganisms were also associated with the clinical characteristics of OSCC, particularly with the clinical outcomes (survival time and status). We developed a predictive model based on this. We found that five different oral microorganisms have high confidence and can be used for clinical diagnosis and prognostic prediction, except for p_Actinobacteria.Conclusion: This study revealed that the intratumor oral microbiota of OSCC patients worldwide and the microbial signatures of OSCC patients possess similar properties in different regions, further refining the shortcomings of the current research field. We revealed that the oral microbiota could be used as a biomarker to reflect human health and disease progression status. This will provide new directions for tumor microbiome research. This means we can develop strategies through diet, probiotics, and antibiotics for cancer prevention and treatment.

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“…An established consensus in the perception of tumors is that neoplastic tissue is likely to act as an organ of greater complexity than otherwise healthy tissue, building up its own microenvironment to boost its varied properties (38,45). Immune cells and stromal cells constitute the mainstay of TME with significant roles in a broad range of aggressive malignant progressions including the proliferation and invasion of tumors and drug resistance (45). A better deciphering of the biological code underlying TME could facilitate better and more precise tumor immunotherapy, which is considered to be a practical and powerful weapon against many refractory malignancies.…”

Section: Discussionmentioning

confidence: 99%

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation

Wang

Zhou

et al. 2023

Front. Immunol.

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More recently, NCAPG2 has emerged as an intrinsically essential participant of the condensin II complex involved in the process of chromosome cohesion and stabilization in mitosis, and its position in particular tumours is now being highlighted. Simultaneously, the genetic properties of NCAPG2 hint that it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. Yet, at present, this recognition remains merely superficial and there is a lack of more detailed studies to explore the underlying pathogenesis. To meet this need, the current study was undertaken to comprehensively elucidate the potential functions of NCAPG2 in pan-cancer, based on a combination of existing databases like TCGA and GTEx. NCAPG2 was identified to be overexpressed in almost every tumor and to exhibit significant prognostic and diagnostic efficacy. Furthermore, the correlation between NCAPG2 and selected immune features, namely immune cell infiltration, immune checkpoint genes, TMB, MSI, etc. also indicates that NCAPG2 could potentially be applied in guidance of immunotherapy. Subsequently, in pancreatic cancer, this study further clarified the utility of NCAPG2 that downregulation of its expression could result in reduced proliferation, invasion and metastasis of pancreatic cancer cells, among such phenotypical changes, the epithelial-mesenchymal transition disruption could be at least one of the possible mechanisms raising or enhancing tumorigenesis. Taken above, NCAPG2, as a member of pan-oncogenes, would serve as a biomarker and potential therapeutic target for a range of malignancies, sharing new insights into precision medicine.

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Turning up a new pattern: Identification of cancer-associated fibroblast-related clusters in TNBC

Cited by 35 publications

References 44 publications

Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

The significant clinical correlation of the intratumor oral microbiome in oral squamous cell carcinoma based on tissue-derived sequencing

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation

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