Relationship between &lt;em&gt;HER2&lt;/em&gt; gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment

Adamczyk, Agnieszka; Kruczak, Anna; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Domagała-Haduch, Małgorzata; Janecka-Widła, Anna; Majchrzyk, Kaja; Cichocka, Anna; Ryś, Janusz; Niemiec, Joanna

doi:10.2147/ott.s166983

Cited by 21 publications

(15 citation statements)

References 45 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, trastuzumab, a humanized monoclonal antibody targeting extracellular region of HER-2, has become the alternative choice in the treatment of HER-2-positive breast cancer 4 . However, only a fraction of metastatic patients responds to trastuzumab and~60% develop resistance after initial response 5 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

et al. 2020

View full text Add to dashboard Cite

Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain-or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Currently, trastuzumab, a humanized monoclonal antibody targeting extracellular region of HER-2, has become the alternative choice in the treatment of HER-2positive breast cancer [4]. However, only a fraction of metastatic patients responds to trastuzumab and approximately 60% develop resistance after initial response [5].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Han¹,

Gu²,

Lü³

et al. 2020

Mol Cancer

146

126

View full text Add to dashboard Cite

Background: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.Methods: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain-or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.Results: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.Conclusion: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

show abstract

“…Human epidermal growth factor receptor 2 (Her2)-positive breast cancer is a highly dangerous breast cancer subtype, accounting for about 15-20% of breast cancer patients [14,15]. Although anti-Her2 targeting drugs such as trastuzumab, pertuzumab and ado-trastuzumab emtansine significantly improved the prognosis of patients with Her2-positive early breast cancer, these drugs not only improved the therapeutic effect, but also increased the treatment cost and adverse reactions [16][17][18]. The exploration of prognostic factors of Her2positive early breast cancer patients and construction of a risk scoring system for prognostic assessment are of great significance for the screening and diagnosis of patients with high risk of recurrence.…”

Section: Discussionmentioning

confidence: 99%

Development of a risk scoring system for evaluating the prognosis of patients with Her2-positive breast cancer

Gao

Zhuang

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: As one of the many breast cancer subtypes, human epidermal growth factor receptor 2 (Her2)-positive breast cancer has higher invasiveness and poor prognosis, although the advent of anti-Her2 drugs has brought good news to patients. However, the emergence of drug resistance still limits its clinical efficacy, so there is an urgent need to explore new targets and develop a risk scoring system to improve treatments and evaluate patient prognosis.Methods: Differentially expressed mRNAs associated with Her2-positive breast cancer were screened from a TCGA cohort. The prognostic risk scoring system was constructed according to univariate and Lasso Cox regression model analyses and combined with clinical factors (such as age and TNM) for univariate and multivariate analyses to verify the specificity and sensitivity of the risk scoring system. Finally, based on correlation and CNV mutation analyses, we explored the research value of the mRNAs involved in the system as key genes of the model. Results:In this study, six mRNAs were screened and identified to construct a prognostic risk scoring system, including four up-regulated mRNA (RDH16, SPC25, SPC24, and SCUBE3) and two down-regulated mRNA (DGAT2 and CCDC69). The risk scoring system can divide Her2-positive breast cancer samples into high-risk and low-risk groups to evaluate patient prognosis. In addition, whether through the time-dependent receiver operating characteristics curve or compared with clinical factors, the risk scoring system showed high predictive sensitivity and specificity. Moreover, some CNV mutations in mRNA increase patient risk by influencing expression levels.Conclusion: The risk scoring system constructed in this study is helpful to improve the screening of high-risk patients with Her2-positive breast cancer and is beneficial for implementing early diagnosis and personalized treatment. It is suggested that these mRNAs may play an important role in the progression of Her2-positive breast cancer.

show abstract

Relationship between <em>HER2</em> gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment

Cited by 21 publications

References 45 publications

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Development of a risk scoring system for evaluating the prognosis of patients with Her2-positive breast cancer

Contact Info

Product

Resources

About