Exploring Collagen Parameters in Pure Special Types of Invasive Breast Cancer

Natal, Rodrigo de Andrade; Paiva, Geisilène Russano de; Pelegati, Vitor B.; Marenco, Ludwing; Alvarenga, César Augusto; Vargas, Renato Flora; Derchain, Sophie; Sarian, Luís Otávio; Franchet, Camille; César, Carlos L.; Schmitt, Fernando; Weigelt, Britta; Vassallo, José

doi:10.1038/s41598-019-44156-9

Cited by 30 publications

(26 citation statements)

References 61 publications

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“…[25][26][27] Furthermore, PPEF1 is involved in a variety of molecular functions related to tumor microenvironment, such as proteases, 28 platelet-derived growth factors and collagen. 29,30 Third, we have innovatively predicted the potential signaling pathways underlying the oncogenic activity of PPEF1 in BC by GSEA. The high expression of PPEF1 is mainly enriched in EMT, angiogenesis, TGF-β pathway, Focal adhesion and ECM receptor interaction (Figure 4, Table 3).…”

Section: Dovepressmentioning

confidence: 99%

The Clinical Significance of PPEF1 as a Promising Biomarker and Its Potential Mechanism in Breast Cancer

Ye¹,

Wan²,

Li³

et al. 2020

OTT

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Background: Breast cancer (BC) is the leading cause of malignancy death in females worldwide. While intense efforts have been made to elucidate the pathogeny, the molecular mechanism of BC remains elusive. Thus, this study aimed to investigate the role of PPEF1 in the progression of BC and further explore the better clinical significance. Methods: The diagnostic and prognostic values of elevated PPEF1 expression in BC were unveiled via public databases analysis. In addition, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and Protein-protein interaction (PPI) analysis were performed to explore the potential functions and molecular mechanisms of PPEF1 in BC progression. Experimentally, transwell and CCK-8 assays were carried out to estimate the effects of PPEF1 on the BC metastasis. Meanwhile, the differential expressions of PPEF1 in paraffin-embedded tissues and serum samples were, respectively, analyzed by Immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) kit. Results: The transcriptional levels of PPEF1 were higher in BC than in normal breast tissues or adjacent normal tissues. Moreover, survival analysis revealed that higher PPEF1 expression was negatively associated with overall survival (OS), all events-free (AE-free) and metastatic recurrence-free (MR-free) survival, and further was an independent risk factor of unfavorable prognosis in BC patients. Additionally, the present study provided the first evidence that PPEF1 participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Furthermore, PPEF1 promotes the BC progression and can be used as a noninvasive diagnostic marker. Noteworthy, the combined determination of serum PPEF1 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of BC. Conclusion: PPEF1 exerted a tumorigenic role and involved in molecular mechanism of tumorigenesis in BC which served as a promising biomarker for prognosis and diagnosis.

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Section: Dovepressmentioning

confidence: 99%

The Clinical Significance of PPEF1 as a Promising Biomarker and Its Potential Mechanism in Breast Cancer

Ye¹,

Wan²,

Li³

et al. 2020

OTT

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“…Little is known about the involvement of CAFs in the biology of ILC, although one study has reported an increased CAF density in ILC compared to matched IDC samples [27], while differences in collagen deposition and alignment have also been reported [28,29]. Our analysis of primary CAFs from ILC and IDC shows differences in a number of genes involved in ECM interactions and signaling pathways, indicating that CAFs are able to differentially in uence the TME in ILC compared to IDC.…”

Section: Discussionmentioning

confidence: 66%

Stromal Transcriptome Analysis of Human Lobular Breast Cancer Identifies a Role for Pregnancy-Associated-Plasma Protein-A

Gómez-Cuadrado

Zhao

Souleimanova

et al. 2020

Preprint

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Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer and exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). Despite these differences, ILC is treated in the same way as IDC. We set out to identify alterations in the tumor microenvironment (TME) of ILC with potential clinical significance.Methods: We used laser-capture microdissection (LCM) to separate tumor epithelium from stroma in 23 ER+ ILC samples. Gene expression analysis was used to identify genes enriched in the stroma of ILC, but not IDC or normal breast. Results: 45 genes involved in regulation of the extracellular matrix (ECM) were enriched in the stroma of ILC, but not stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets. PAPPA was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. PAPPA encodes pregnancy-associated plasma protein-A (PAPP-A), a metalloproteinase that cleaves insulin-like growth factor-binding protein-4 (IGFBP-4), increasing IGF-1 bioavailability and downstream signaling. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. Comprehensive survival analysis across 3,000 breast cancers identified PAPPA as a potential ILC-specific prognostic marker.Conclusions: This is the first study to demonstrate molecular differences in the TME between ILC and IDC, and it identifies PAPP-A, a CAF-derived proteinase, as a potential prognostic marker.

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“…CAFs are an important component of the TME that regulate ECM deposition and secrete cytokines and growth factors to control metastatic spread and therapeutic response [26]. However, little is known about the involvement of CAFs in the biology of ILC, although one study has reported an increased CAF density in ILC compared to matched IDC samples [27], while differences in collagen deposition and alignment have also been reported in ILC [28,29]. Our analysis of primary CAFs from ILC and IDC shows differences in a number of genes involved in ECM interactions and signaling pathways indicating that CAFs are able to differentially influence the TME in ILC compared to IDC.…”

Section: Discussionmentioning

confidence: 99%

Identification of stromal genes differentially expressed in lobular breast cancer highlights role for pregnancy-associated-plasma protein-A

Gómez-Cuadrado

Zhao

Souleimanova

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer and exhibits a number of clinico-pathological characteristics that are distinct from the more common invasive ductal carcinoma (IDC). Despite these differences, ILC is treated in the same way as IDC. We set out to identify alterations in the tumor microenvironment (TME) of ILC with potential clinical significance. Methods:We used laser-capture microdissection (LCM) to separate tumor epithelium from stroma in 23 ER+ ILC samples. Gene expression analysis was used to identify genes that are enriched in the stroma of ILC, but not IDC or normal breast.Results: 45 genes involved in regulation of the extracellular matrix (ECM) were enriched in the stroma of ILC, but not stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets. PAPPA was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. PAPPA encodes pregnancy-associated plasma protein-A (PAPP-A), a metalloproteinase that cleaves insulin-like binding protein-4 (IGFBP-4) increasing IGF-1 bioavailability and subsequent downstream signaling. Analysis of PAPPA and IGF1 associated genes identified a paracrine signaling pathway and active PAPP-A was shown to be secreted from primary CAFs. Comprehensive survival analysis across 3000 breast cancers identified PAPPA as a potential ILC-specific prognostic marker.Conclusions: This is the first study to demonstrate molecular differences in the TME between ILC and IDC and identifies PAPP-A, a CAF-derived proteinase, as a potential prognostic marker.

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Exploring Collagen Parameters in Pure Special Types of Invasive Breast Cancer

Cited by 30 publications

References 61 publications

<p>The Clinical Significance of <em>PPEF1</em> as a Promising Biomarker and Its Potential Mechanism in Breast Cancer</p>

<p>The Clinical Significance of <em>PPEF1</em> as a Promising Biomarker and Its Potential Mechanism in Breast Cancer</p>

Stromal Transcriptome Analysis of Human Lobular Breast Cancer Identifies a Role for Pregnancy-Associated-Plasma Protein-A

Identification of stromal genes differentially expressed in lobular breast cancer highlights role for pregnancy-associated-plasma protein-A

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