CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

Baldacchino, Shawn; Wastall, Laura M; Saliba, Christian; Hughes, Tom; Scerri, Christian; Berwick, Angelene; Speirs, Valerie; Hanby, Andrew M.; Grech, Godfrey

doi:10.1177/1010428317722064

Cited by 4 publications

(5 citation statements)

References 48 publications

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“…Furthermore, a significant association was observed between high CIP2A expression and HER-2 positivity, ER and PR negativity. Many studies reported association of high CIP2A expression with poor prognostic factors [36,37,38,39] and recurrence after treatment [18].…”

Section: Discussionmentioning

confidence: 99%

“…The clinical relevance of CIP2A overexpression as a prognostic marker has been established in various solid and hematological malignancies, including, chronic myelogenous leukemia, bladder carcinoma, non-small cell lung cancer, multiple myeloma, and endometrioid adenocarcinoma [13,14,15,16,17]. Regarding breast cancer, CIP2A expression has been correlated with aggressiveness and also predicts a worse prognosis [18].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of CIP2A and ROCK-I expression and their prognostic value in breast cancer

Osman¹,

Khalaf²,

Ibraheem³

2020

pjp

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Breast cancer is the most leading cause of cancer death in females worldwide. Identification of novel biomarkers for prognosis is required. Imunohistochemical evaluation of CIP2A and ROCK-1 expressions in 126 breast tissue specimens stratified as 21 ductal hyperplasias, 17 duct carcinoma in situ (DCIS) and 88 invasive carcinomas (56 invasive ductal carcinomas NST, 32 invasive lobular carcinomas) was studied. High CIP2A expression was detected in 48.9% of invasive carcinomas. CIP2A overexpression was significantly related to Nottingham prognostic index (NPI) (p = 0.011), stage (p = 0.01), ER negativity (p = 0.031), PR negativity (p = 0.048), and HER-2 positivity (p = 0.02). CIP2A was significantly overexpressed in triple-negative breast cancer (TNBC) (p = 0.004). ROCK-1 expression was detected in 54.5% of invasive carcinomas. Statistically significant associations were observed between ROCK-1 expression and NPI (p = 0.032), stage (p = 0.002), ER negativity (p = 0.012), PR negativity (p = 0.023), HER-2 positivity (p = 0.016), and TNBC subtype (p = 0.033). A positive association between CIP2A and ROCK-1 expressions (p < 0.0001) was documented. There was a significant association between shorter overall survival and high CIP2A and positive ROCK-1 expressions (p < 0.0001) and (p < 0.0001). CIP2A and ROCK-1 expressions could be used as markers for the poor prognosis of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment of CIP2A and ROCK-I expression and their prognostic value in breast cancer

Osman¹,

Khalaf²,

Ibraheem³

2020

pjp

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“…At the clinical level, CIP2A overexpression hasbeen reported to predict poor outcome in breast cancer [ 12 , 25 ], with a special relevance in the TN subtype [ 26 , 27 ]. Moreover, CIP2A expression has also been described as a predictive marker of recurrence in tamoxifen-treated breast cancer patients [ 28 ]. The high relevance of the CIP2A/AKT interplay has been largely reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer

Luque

Cristóbal

Sanz-Álvarez

et al. 2022

JCM

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Together with its reported ability to modulate AKT phosphorylation (p-AKT) status in several tumor types, the oncoprotein CIP2A has been described to induce breast cancer progression and drug resistance. However, the clinical and therapeutic relevance of the CIP2A/AKT interplay in breast cancer remains to be fully clarified. Here, we found high p-AKT levels in 80 out of 220 cases (36.4%), which were associated with negative estrogen receptor expression (p = 0.049) and CIP2A overexpression (p < 0.001). Interestingly, p-AKT determined substantially shorter overall (p = 0.002) and progression-free survival (p = 0.003), and multivariate analyses showed its CIP2A-independent prognostic value. Moreover, its clinical relevance was further confirmed in the triple negative and HER2-positive subgroups after stratifying our series by molecular subtype. Functionally, we confirmed in vitro the role of CIP2A as a regulator of p-AKT levels in breast cancer cell lines, and the importance of the CIP2A/AKT axis was also validated in vivo. Finally, p-AKT also showed a higher predictive value of response to doxorubicin than CIP2A in ex vivo analyses. In conclusion, our findings suggest that CIP2A overexpression is a key contributing event to AKT phosphorylation and highlights the CIP2A/AKT axis as a promising therapeutic target in breast cancer. However, our observations highlight the existence of alternative mechanisms that regulate AKT signaling in a subgroup of breast tumors without altered CIP2A expression that determines its independent value as a marker of poor outcome in this disease.

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“…It has been determined that the levels of this protein are over-expressed in human breast cancer tissues, so its presence allows the diagnosis and prognosis of breast cancer, therefore it is useful as a diagnostic marker for this disease, in addition to being detectable in blood, which gives it greater value, as it is easily detectable [3,4]. It has been found that tamoxifen-induced apoptosis in breast cancer is associated with the down-regulation of CIP2A and p-AKT, likewise the membranous expression of CIP2A is significantly higher in patients with tamoxifen resistance, however the mechanism by which resistance is generated is not yet fully glimpsed [35].…”

Section: Cancerous Inhibitor Of the Protein Phosphatase 2a (Cip2a)mentioning

confidence: 99%

“…Membranous CIP2A is an indicator of resistance to tamoxifen in breast cancer with positive hormone receptors. It is considered that it may be useful to select patients with positive estrogen receptor at risk of developing resistance to tamoxifen [35].…”

Section: Cancerous Inhibitor Of the Protein Phosphatase 2a (Cip2a)mentioning

confidence: 99%

Genes and proteins associated with chemotherapeutic resistance in breast cancer

Linares¹,

Benítez²,

Avila³

2018

Calcified Constrictive Pericarditis Treated With Ultrasonic Devices

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Breast cancer is the main type of cancer that affects women in the world. Treatment with chemotherapeutic agents for this type of cancer depends to a large extent on the phenotypic characteristics that appear in the tumor, such as some receptors. The treatment of breast cancer is complex since not all patients respond adequately to it and this is partly due to mechanisms of resistance to treatment. The resistance either acquired or intrinsic to chemotherapeutics against breast cancer is related to multiple genes and proteins that are actively involved in the development of resistance mechanisms, which may be inhibiting the binding of the drug to the target receptor, inhibiting the gene expression of the receptors, activating signaling pathways, inducing the action of transporters that expel the drug from the cell, etc. As a result of this review, the mechanisms of chemotherapeutic resistance in breast cancer derived from genes and proteins related to say disease are described, including genes related to different types of breast cancer, as well as with different therapeutic strategies. These genes and their products of expression include a wide range of interactions and activations of signalling pathways that trigger a poor response to treatment, which translates into a worse prognosis, higher risk of prevalence and death, favouring breast cancer to be the main cause of cancer death in women. Objective: Conduct an updated review of genes and proteins, that have been associated with conferring resistance to the different chemotherapeutic agents used for the treatment of breast cancer, including the mechanism of resistance and the type of cancer in which it is generated. Method: The search for indexed articles in the PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) and ScienceDirect (http://www.sciencedirect.com) databases was performed, using the words "Breast cancer resistance" as a search criterion, articles published in the period 2015-2017 were selected.

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CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

Cited by 4 publications

References 48 publications

Assessment of CIP2A and ROCK-I expression and their prognostic value in breast cancer

Assessment of CIP2A and ROCK-I expression and their prognostic value in breast cancer

CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer

Genes and proteins associated with chemotherapeutic resistance in breast cancer

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