Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

Zehni, Alaleh Zati; Batz, Falk; Cavaillès, Vincent; Sixou, Sophie; Kaltofen, Till; Keckstein, Simon; Heidegger, H; Ditsch, Nina; Mahner, Sven; Jeschke, Udo; Vilsmaier, Theresa�

doi:10.3390/cancers13153756

Cited by 7 publications

(10 citation statements)

References 66 publications

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“…Within this study, we combined the analysis of TIL levels (following Salgado’s guidelines), peritumoral inflammation (adapted from Klintrup criteria), and nuclear receptor expression in a cohort of BC in relation to patient overall survival (OS). Taking into account both nuclear and cytoplasmic expression of type I and II nuclear receptors, as former studies already showed a prognostic impact of nuclear receptor subcellular localization [ 40 ], our results highlight a strong interplay of the two parameters, which determines their prognosis value for BC patients. Next to the influence of TILs on tumor progression and prognosis, the nuclear receptors and their subcellular localization play notable roles in the pathophysiology of BC as well [ 34 , 42 ].…”

Section: Discussionsupporting

confidence: 62%

“…Using the above-described BC cohort, the expression of type I and type II nuclear receptors has been previously analyzed by immunohistochemistry by our group. Information was specifically evaluated regarding ERα and PR [ 34 ], PPARγ [ 35 ], thyroid hormone receptors (TRs) [ 36 , 37 ], AhR [ 33 ], LXR [ 38 ], and RXRα [ 39 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

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Prognostic Relevance of Nuclear Receptors in Relation to Peritumoral Inflammation and Tumor Infiltration by Lymphocytes in Breast Cancer

Köpke

Château²,

Boissière³

et al. 2022

Cancers

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The prognostic impact of tumor-infiltrating lymphocytes (TILs) is intensively investigated in breast cancer (BC). It is already known that triple-negative breast cancer (TNBC), the most aggressive type of BC, has the highest percentage of TILs. In addition, there is an influence of steroid hormone receptor expression (type I nuclear receptors) on TIL subpopulations in breast cancer tissue. The link between type II nuclear receptors and the level of TILs is unclear. Therefore, the aim of this study was to quantify TILs in a panel of 264 sporadic breast cancers and investigate the correlation of TIL levels with type I and II nuclear receptors expression. TIL levels were significantly increased in the subgroup of TNBC. By contrast, they decreased in estrogen (ER)- or progesterone receptor (PR)-positive cases. Moreover, TIL levels were correlated with type II nuclear receptors, including PPARγ, with a significant inverse correlation of the nuclear form (r = −0.727, p < 0.001) and a weak positive correlation of the cytoplasmic form (r = 0.202, p < 0.002). Surprisingly, BC cases with a TIL Salgado score of >15% showed a significantly decreased overall survival. In addition, peritumoral inflammation was also quantified in BC tissue samples. In our cohort, although the level of peritumoral inflammation was not correlated with OS, it determined the prognostic value of ER, PR, and PPARγ in BC. Altogether, the present study provides a differentiated overview of the relations between nuclear receptor expression, TIL levels, peritumoral inflammation, and prognosis in BC.

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Section: Discussionsupporting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Prognostic Relevance of Nuclear Receptors in Relation to Peritumoral Inflammation and Tumor Infiltration by Lymphocytes in Breast Cancer

Köpke

Château²,

Boissière³

et al. 2022

Cancers

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“…Of note, various types of addiction to specific transcriptional programs and/or kinase activities appear to operate in specific subsets of cancer and are thought to deeply contribute to cancer pathogenesis [77,78]. Interestingly, when a more accurate and stringent analysis was performed on the regulated target genes of these two candidate miRNAs, Mienturnet analysis followed by MetaCore process networks revealed the presence of important central hubs, including the transcriptional factors SP1 (specificity protein 1), RXRA (retinoid X receptor alpha), and BMI-1 (polycomb ring finger proto-oncogene) and the epidermal growth factor receptor kinase EGFR, with multiple roles in breast cancer development and progression [79][80][81][82]. Moreover, Metacore gene enrichment analysis indicated the involvement of the 18 target genes in cell cycle transition from G2 to M, the follicle-stimulating hormone (FSH) beta signaling pathway, androgen receptor signaling cross-talk, NOTCH signaling, ESR1 nuclear pathway and signaling, and EMT among the top enriched processes.…”

Section: Discussionmentioning

confidence: 99%

miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer

Giordano,

Accattatis,

Gelsomino

et al. 2023

IJMS

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Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.

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“…Besides the well-known nuclear receptors, others, including the retinoid X receptor (RXR), thyroid hormone receptors and vitamin D receptor, play a significant role in the pathophysiology of breast cancer. The study by Zheni et al aimed to assess the prognostic value of nuclear versus cytoplasmic retinoid X receptor α (RXRα) expression by immunohistochemistry in 319 breast cancer patients [ 11 ]. In their findings, the expression of cytoplasmic RXRα is correlated with a more aggressive disease, whereas nuclear RXRα expression appears to be a protective factor.…”

mentioning

confidence: 99%