Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer

Chen, J. Q.; Bao, Yi; Lee, John; Murray, Juliette; Litton, Jennifer; Xiao, Li; Zhou, Renke; Wu, Yun; Shen, Xıaoyun; Zhang, H.; Şahin, Ayşegül; Katz, Ruth L.; Bondy, Melissa L.; Berinstein, Neil L.; Hortobágyi, Gabriel N.; Radvanyi, Laszlo G.

doi:10.1093/annonc/mdt190

Cited by 18 publications

(15 citation statements)

References 49 publications

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“…Surprisingly, in ERα-positive breast cancer, we found TRPS1 to be positively associated with E-cadherin and β-catenin status with no significant correlation with any of the mesenchymal markers. Consistent with our hypothesis, significant association was also found between TRPS1 expression and E-cadherin expression in ERα + breast cancer cases [32]. In ERα-negative breast cancer, we found TRPS1 to be positively associated with vimentin, SMA and slug.…”

Section: Discussionsupporting

confidence: 90%

Association of TRPS1 gene with different EMT markers in ERα-positive and ERα-negative breast cancer

Zhang

et al. 2014

Diagn Pathol

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BackgroundBreast cancer is a heterogeneous disease consisting of different subtypes. Trichorhinophalangeal syndrome type 1 (TRPS1) gene, a GATA-type transcription factor, has been found to be highly expressed in breast cancer. Epithelial-to-mesenchymal transition (EMT) is known to play an important role in tumour invasion and metastasis. Our objective was to elucidate the different roles and clinical relevance of TRPS1 in different estrogen receptor (ER) expression subtypes of breast cancer.MethodsAn immunohistochemical study was performed. The correlation between clinicopathological features and other biomarker profiles were analysed statistically.ResultTRPS1 expression was correlated with the patients’ age (P = 0.017). It was positively related with ERα (P < 0.001), progesterone receptor (PR) (P < 0.001) and ERβ (P = 0.001) status, but negatively associated with Ki67 (P = 0.002) and HER2 (P = 0.025) status. In ERα-positive breast cancer, TRPS1 expression was positively associated with the expression of E-cadherin (P < 0.001), β-catenin(P = 0.001), ERβ (P = 0.03), and p53 (P = 0.002) status, while in ERα-negative breast cancer, TRPS1 expression was correlated with slug (P = 0.004), vimentin (P = 0.003), smooth muscle actin (SMA) (P = 0.031), and IMP3 (P = 0.005) expression.ConclusionsBased on our findings, we conclude that TRPS1 is positively associated with E-cadherin and β-catenin status in ERα-positive breast cancer cells, while it is also significantly associated with mesenchymal markers of EMT in ERα-negative breast cancer cells. TRPS1 can be a prognostic marker depending on the type of breast cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8686515681264281

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Section: Discussionsupporting

confidence: 90%

Association of TRPS1 gene with different EMT markers in ERα-positive and ERα-negative breast cancer

Zhang

et al. 2014

Diagn Pathol

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“…In sporadic breast cancer TRPS1 is linked to the stimulation of cell proliferation and angiogenesis and the promotion of cell cycle progression . Furthermore, TRPS1 overexpression was proposed as a prognostic marker in early stage breast cancer due to an association with improved overall survival and disease‐free survival in these tumors . Moreover, TRPS1 expression was found to correlate with ER, PgR, Ki67, GATA‐3 and Her2 expression, which we could not confirm in our data .…”

Section: Discussioncontrasting

confidence: 82%

“…7,10,12 Furthermore, TRPS1 overexpression was proposed as a prognostic marker in early stage breast cancer due to an association with improved overall survival and disease-free survival in these tumors. 35 Moreover, TRPS1 expression was found to correlate with ER, Figure 3. Significantly increased TRPS1 protein expression represented by the marker staining intensity was observed in breast cancer tissues from the nonexposed groups (light blue) compared to the exposed groups (purple) in the discovery (a, p 5 0.028) and validation cohorts (b, p 5 0.027).…”

Section: Discussionmentioning

confidence: 96%

Expression of miRNA‐26b‐5p and its target TRPS1 is associated with radiation exposure in post‐Chernobyl breast cancer

Wilke

Heß

Klymenko

et al. 2017

Intl Journal of Cancer

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Ionizing radiation is a well-recognized risk factor for the development of breast cancer. However, it is unknown whether radiation-specific molecular oncogenic mechanisms exist. We investigated post-Chernobyl breast cancers from radiation-exposed female clean-up workers and nonexposed controls for molecular changes. Radiation-associated alterations identified in the discovery cohort (n = 38) were subsequently validated in a second cohort (n = 39). Increased expression of hsa-miR-26b-5p was associated with radiation exposure in both of the cohorts. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of hsa-miR-26b-5p, was associated with radiation exposure. As TRPS1 overexpression is common in sporadic breast cancer, its observed downregulation in radiation-associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. For this purpose, the impact of TRPS1 on the transcriptome was characterized in two radiation-transformed breast cell culture models after siRNA-knockdown. Deregulated genes upon TRPS1 knockdown were associated with DNA-repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. Furthermore, we identified the interaction partners of TRPS1 from the transcriptomic correlation networks derived from gene expression data on radiation-transformed breast cell culture models and sporadic breast cancer tissues provided by the TCGA database. The genes correlating with TRPS1 in the radiation-transformed breast cell lines were primarily linked to DNA damage response and chromosome segregation, while the transcriptional interaction partners in the sporadic breast cancers were mostly associated with apoptosis. Thus, upregulation of hsa-miR-26b-5p and downregulation of TRPS1 in radiation-associated breast cancer tissue samples suggests these molecules representing radiation markers in breast cancer.

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“…S8A). This is in agreement with previous reports showing that TRPS1 is a positive prognostic marker in ER+ breast cancer (51). Luminal B and basal-like breast cancer patients with reduced expression of TRPS1 showed a negative trend in survival, but the results do not reach statistical significance (Fig.…”

Section: Trps1 Expression Levels Are Clinically Associated With Patientsupporting

confidence: 92%

Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

Rangel

Lee

Ban

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.Sleeping Beauty | breast cancer | TRPS1 | metastasis | tumor suppressors B reast cancer is the second leading cause of cancer-related deaths in the United States. The Cancer Genome Atlas (TCGA) network has classified breast cancer into four main subtypes: luminal A, luminal B, HER2+, and basal-like (1-5). Basal-like or triplenegative breast cancer (TNBC) constitutes 10-20% of all breast cancers and has a higher rate of distal recurrence and a poorer prognosis than other breast cancer subtypes. Less than 30% of women with metastatic TNBC survive 5 y and almost all die from their disease despite adjuvant chemotherapy (1, 3-5). Mutations, rearrangements, or deletions in highly penetrant genes such as BRCA1, BRCA2, TP53, CDH1, STK11, and PTEN are important drivers of TNBC (6-8). PTEN is a dual-specificity phosphatase that antagonizes the PI3K/AKT pathway through its lipid phosphatase activity and negatively regulates the MAPK pathway through its protein phosphatase activity (9, 10). Mutations in PTEN drive epithelial-mesenchymal transition (EMT) and promote metastasis in TNBC (11-13). Similarly, in mice, heterozygous deletion of Pten induces mammary tumors with basal-like characteristics (14)(15)(16)(17).Despite all of the cancer genome-sequencing efforts, there is still an incomplete understanding of the genes and genetic networks driving TNBC. New technologies that would provide a more complete understanding of the genetics of TNBC are still needed to deconvolute the complexity of this deadly cancer. Our laboratory and others have pioneered the use of transposon mutagenesis in mice as a tool for cancer gene discovery (18-26). Transposons induce cancer by randomly inserting into the mouse genome, mutating, and disrupting potential cancer genes. Transposon insertions in tumors thus serve as molecular tags for the high-throughput cloning and identification of cancer genes. In addition, because transposon insertions are PCR-amplified before they are sequenced, insertional mutations in cancer genes that are present in only a small fraction of tumor cells can be identified. Transposon mutagenesis can thus identify genes that are functioning at th...

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Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer

Abstract: Our data indicated that TRPS-1 is an independent prognostic marker in early-stage BC and a new EMT marker that can distinguish patients with ER+ BC who will respond longer to adjuvant endocrine therapy.

Cited by 18 publications

References 49 publications

Association of TRPS1 gene with different EMT markers in ERα-positive and ERα-negative breast cancer

Association of TRPS1 gene with different EMT markers in ERα-positive and ERα-negative breast cancer

Expression of miRNA‐26b‐5p and its target TRPS1 is associated with radiation exposure in post‐Chernobyl breast cancer

Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

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