bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses

Jézéquel, Pascal; Frenel, Jean‐Sébastien; Campion, Loı̈c; Guérin‐Charbonnel, Catherine; Gouraud, Wilfried; Ricolleau, G.; Campone, Mario

doi:10.1093/database/bas060

Cited by 205 publications

(180 citation statements)

References 23 publications

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“…First, a positive correlation between PNR and IL-13Rα2 mRNA levels ( r = 0.24, P <0.0001; Figure 5a) was observed using the bc-GenExMiner database with a collection of 3161 breast cancer patients. 25 The correlation coefficient is comparable to that of PNR and ERα ( n = 2872, r = 0.26, P <0.0001) (Supplementary Figure S2A), which has been shown to have positive correlation. 4 IL-13 signals through two membrane-bound receptors, IL-13Rα1 and IL-13Rα2.…”

Section: Resultssupporting

confidence: 55%

IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer

Zhao

Wang

2014

Oncogene

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Emerging evidence has linked photoreceptor cell-specific nuclear receptor (PNR/NR2E3), an orphan nuclear hormone receptor, to human breast cancer. PNR was shown to be a transcriptional activator of estrogen receptor-α (ERα) in ERα-positive breast cancer cell lines and high-level expression of PNR correlates with favorable response of ERα-positive breast cancer patients to tamoxifen. Interestingly, gene expression microarray study shows that PNR regulates distinct genes from those regulated by ERα, suggesting that PNR could have ERα-independent functions. Herein, we investigated the function of PNR in ERα-negative breast cancer cells. Our results showed that PNR-induced cell migration and metastasis of ERα-negative breast cancer cells both in vitro and in vivo, and the effect was attributed to the upregulation of interleukin (IL)-13Rα2, a high-affinity receptor for IL-13 that regulates tumor growth, invasion and metastasis of various human cancers. Mechanistically, PNR activated transcription of IL-13Rα2 through direct recruitment to IL-13Rα2 promoter. Upon stimulation with IL-13, IL-13Rα2 increased the extracellular signal-regulated kinases 1 and 2 phosphorylation, which led to breast cancer migration and metastasis. The IL-13 triggered signal cascade was specific to IL-13Rα2, as the closely related IL-13Rα1 was not regulated by PNR. IL-13Rα2 is a novel tumor antigen that is overexpressed in a variety of solid tumor types. This study presents the first evidence that PNR could promote ERα-negative breast cancer metastasis through activation of IL-13Rα2-mediated signaling pathway.

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Section: Resultssupporting

confidence: 55%

IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer

Zhao

Wang

2014

Oncogene

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“…1B; Pawitan et al 2005). Further large-scale gene expression analyses of the hPAFc subunits were performed on >1000 primary breast cancers using the Breast Cancer Gene Expression Miner 3.0 (bc-GenExMiner 3.0) online tool (Jézéquel et al 2013). Similar to the ESR1 gene encoding the ERα protein, which is the major molecular determinant of luminal breast cancer, CTR9 mRNA expression is highly enriched in the luminal subtypes (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis

Zeng

2015

Genes Dev.

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The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold subunit in hPAFc, is highly expressed in estrogen receptor α-positive (ERα + ) luminal breast cancer, and the high expression of Ctr9 correlates with poor prognosis. Knockdown of Ctr9 in ERα + breast cancer cells almost completely erased estrogen-regulated transcriptional response. At the molecular level, Ctr9 enhances ERα protein stability, promotes recruitment of ERα and RNAPII, and stimulates transcription elongation and transcription-coupled histone modifications. Knockdown of Ctr9, but not other hPAFc subunits, alters the morphology, proliferative capacity, and tamoxifen sensitivity of ERα + breast cancer cells. Together, our study reveals that Ctr9, a key subunit of hPAFc, is a central regulator of estrogen signaling that drives ERα + breast tumorigenesis, rendering it a potential target for the treatment of ERα + breast cancer.

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“…Breast Cancer Gene-Expression Miner v4.0 (bcGenExMiner v4.0) is a statistical mining tool of 36 noted genomic datasets and three classical mining functions: expression, prognosis, and correlation [11, 12]. Expression data was updated in March 2016 and compares production of a particular gene with clinical parameters such as age, ER, PR, HER2, and so on.…”

Section: Methodsmentioning

confidence: 99%

Identification of Potential Therapeutic Targets Among CXC Chemokines in Breast Tumor Microenvironment Using Integrative Bioinformatics Analysis

Chen

Qin

Peng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Breast cancer is a common cause of cancer mortality throughout the world. The cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC is one of four chemokine families involved in mediating survival, angiogenesis, and immunosensitization by chemoattracting leukocytes, and it incentivizes tumor cell growth, invasion and metastasis in the tumor microenvironment. However, the differential expression profiles and prognostic values of these chemokines remains to be elucidated. Methods: In this study, we compared transcriptional CXC chemokines and survival data of patients with breast carcinoma (BC) using the ONCOMINE dataset, Kaplan-Meier Plotter, TCGA and cBioPortal. Results: We discovered increased mRNA levels for CXCL8/10/11/16/17, whereas mRNA expression of CXCL1/2/3/4/5/6/7/12/14 was lower in BC patients compared to non-tumor tissues. Kaplan-Meier plots revealed that high mRNA levels of CXCL1/2/3/4/5/6/7/12/14 correlate with relapse-free survival (RFS) in all types of BC patients. Conversely, high CXCL8/10/11 predicted worse RFS in BC patients. Significantly, high transcription levels of CXCL9/12/13/14 conferred an overall survival (OS) advantage in BC patients, while high levels of CXCL8 demonstrated shorter OS in all BC sufferers. Conclusions: Integrative bioinformatics analysis suggests that CXCL8/12/14 are potential suitable targets for precision therapy in BC patients compared to other CXC chemokines.

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bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses

Cited by 205 publications

References 23 publications

IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer

IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer

Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis

Identification of Potential Therapeutic Targets Among CXC Chemokines in Breast Tumor Microenvironment Using Integrative Bioinformatics Analysis

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