Analysis of genomics and immune infiltration patterns of epithelial-mesenchymal transition related to metastatic breast cancer to bone

Liu, Shuzhong; An, Shi; Wu, Yunxiao; Yao, Siyuan; Wang, Muchuan; Niu, Tong; Gao, Chengao; Li, Ziquan; Zhou, Xi; Huo, Zhen; Yang, Bo; Liu, Yong; Wang, Yipeng

doi:10.1016/j.tranon.2020.100993

Cited by 30 publications

(27 citation statements)

References 36 publications

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“…Some of them be related to TGFB signaling pathway. Such as, FERMT2 (FERM domain containing kindlin 2), have TGFBR1 binding activity, 42 Involved in cell surface receptor signaling pathway. 42 DIXDC1 (DIX domain containing 1), is a positive regulator of the Wnt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Such as, FERMT2 (FERM domain containing kindlin 2), have TGFBR1 binding activity, 42 Involved in cell surface receptor signaling pathway. 42 DIXDC1 (DIX domain containing 1), is a positive regulator of the Wnt signaling pathway. 43 ABCC9 (ATP binding cassette subfamily C member 9), is a member of the MRP subfamily which is involved in multi-drug resistance.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Characterization of Transforming Growth Factor Beta Receptor 1 in Stomach Adenocarcinoma Identifies a Prognostic Signature for Predicting Clinical Outcomes and Immune Infiltrates

He¹,

Zhang²,

Zhang³

et al. 2022

IJGM

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Background Stomach adenocarcinoma (STAD) ranks as the third leading cause of cancer death worldwide. TGF‑β receptor 1 (TGFBR1), serving important roles in the TGF‑β family, the mechanisms whereby TGFBR1 governs tumor progression, immune cell infiltration in STAD remains unintelligible. Methods We used the TCGA, GEPIA, and HPA databases to explore TGFBR1 expression in STAD, the correlation between TGFBR1 expression and the clinical features. A receiver operating characteristic (ROC) curve and nomogram were constructed, and LASSO (the Least Absolute Shrinkage and Selection Operator)-selected features were used to build the TGFBR1 prognostic signature. GSEA is used to find the potential mechanism of TGFBR1 to promote the malignant process of STAD. We explored the influence of the TGFBR1 on the immune microenvironment of STAD through the TIMER2.0 and GEPIA database. Results In our study, TGFBR1 expression was significantly elevated in STAD and positively co-expression with pathologic stage, lymph node metastases (LNM) stage and histopathological grade. Nine factors with non-zero coefficients were identified by LASSO-selected features. Survival analysis revealed that patients with high TGFBR1 had shorter OS, FP, and PPS. Multivariate Cox analysis revealed that TGFBR1 was an independent prognostic factor for OS in STAD. The ROC analysis suggested that high diagnostic value with the AUC of TGFBR1 was 0.739. GSEA revealed that high TGFBR1 expression was correlated with pathway in cancer, MAPK signaling pathway, NOTCH signaling pathway, and VEGF-C production. ssGSEA showed that TGFBR1 is correlated with NK cells, Tem and Th17 cells. Furthermore, elevated TGFBR1 expression was found to be significantly correlated with several immune checkpoint and immune markers associated with immune cell subsets. Conclusion In summary, TGFBR1 could be a prognostic biomarker and an important regulator of immune cell infiltration in STAD. The present study revealed the probable underlying molecular mechanisms of TGFBR1 in STAD and provided a potential target for improving the prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive Characterization of Transforming Growth Factor Beta Receptor 1 in Stomach Adenocarcinoma Identifies a Prognostic Signature for Predicting Clinical Outcomes and Immune Infiltrates

He¹,

Zhang²,

Zhang³

et al. 2022

IJGM

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“…Estrogens reduce the cytotoxic activity (production of granzymes and FasL) of mature NK cells, likely through the down-regulation of their activation receptors (NKp46, NKG2D/L) and the increased expression of the inhibiting receptor CD94 ( 106 ). However in the bone, no effect of NK on BMet progression has clearly been documented ( 107 ). Hence, the reduced cytotoxic function of NK cells in response to estrogens likely increases the number of disseminated cells in the blood that could reach the bone, but do not contribute to the metastasis immune escape once settled in the bone.…”

Section: Estrogen and Lymphoid Cellsmentioning

confidence: 99%

Effects of Estrogens on Osteoimmunology: A Role in Bone Metastasis

Marie

Bonnelye

2022

Front. Immunol.

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Bone loss associated with estrogen deficiency indicates a fundamental role of these hormones in skeletal growth and bone remodeling. In the last decades, growing recent evidence demonstrated that estrogens can also affect the immune compartment of the bone. In this review, we summarize the impacts of estrogens on bone immune cells and their consequences on bone homeostasis, metastasis settlement into the bone and tumor progression. We also addressed the role of an orphan nuclear receptor ERRalpha (“Estrogen-receptor Related Receptor alpha”) on macrophages and T lymphocytes, and as an immunomodulator in bone metastases. Hence, this review links estrogens to bone immune cells in osteo-oncology.

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“…P <0.05 was considered statistically signi cant. WGCNA WGCNA is a systemic method that uses gene expression data to build a scale-free network [13]. A weighted co-expression network with the expression pro le data of the DEGs was built using the WGCNA package of R. Following this, we screened the key module related to BC bone metastasis and prognosis, and then extracted the genes for further analysis.…”

Section: Identi Cation and Functional Enrichment Analysis Of Degsmentioning

confidence: 99%

Nomogram Models Based on Gene Expression in Prediction of Breast Cancer Bone Metastasis

Fan

Bei

2021

Preprint

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Objective: To design a weighted co-expression network and build gene expression signature-based nomogram (GESBN) models for predicting the likelihood of bone metastasis in breast cancer (BC) patients. Methods: Dataset GSE124647 was used as a training set, and GSE14020 was taken as a validation set. In the training cohort, limma package in R was adopted to obtain differentially expressed genes (DEGs) between BC non-bone metastasis and bone metastasis patients, which were used for functional enrichment analysis. After weighted co-expression network analysis (WGCNA), univariate Cox regression and Kaplan-Meier plotter analyses were performed to screen potential prognosis-related genes. Then, GESBN models were constructed and evaluated. Further, the expression levels of genes in the models were explored in the training set, which was validated in GSE14020. Finally, the prognostic value of hub genes in BC was explored. Results: A total of 1858 DEGs were obtained. WGCNA result showed that the blue module was most significantly related to bone metastasis and prognosis. After survival analyses, GAJ1, SLC24A3, ITGBL1, and SLC44A1 were subjected to construct a GESBN model for overall survival. While GJA1, IGFBP6, MDFI, ITGFBI, ANXA2, and SLC24A3 were subjected to build a GESBN model for progression-free survival. Kaplan-Meier plotter and receiver operating characteristic analyses presented the reliable prediction ability of the models. Besides, GJA1, IGFBP6, ITGBL1, SLC44A1, and TGFBI expressions were significantly different between the two groups in GSE124647 and GSE14020. The hub genes had a significant impact on patient prognosis. Conclusion: Both the four-gene signature and six-gene signature could accurately predict patient prognosis, which may provide novel treatment insights for BC bone metastasis.

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Analysis of genomics and immune infiltration patterns of epithelial-mesenchymal transition related to metastatic breast cancer to bone

Cited by 30 publications

References 36 publications

Comprehensive Characterization of Transforming Growth Factor Beta Receptor 1 in Stomach Adenocarcinoma Identifies a Prognostic Signature for Predicting Clinical Outcomes and Immune Infiltrates

Comprehensive Characterization of Transforming Growth Factor Beta Receptor 1 in Stomach Adenocarcinoma Identifies a Prognostic Signature for Predicting Clinical Outcomes and Immune Infiltrates

Effects of Estrogens on Osteoimmunology: A Role in Bone Metastasis

Nomogram Models Based on Gene Expression in Prediction of Breast Cancer Bone Metastasis

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