scholarly journals Discordance of PD-L1 Expression at the Protein and RNA Levels in Early Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4655
Author(s):  
Ioannis Zerdes ◽  
Vaia Karafousia ◽  
Artur Mezheyeuski ◽  
Maria Stogiannitsi ◽  
Raoul Kuiper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Early Breast Cancer ◽  
Simultaneous Detection ◽  
Tissue Microarrays ◽  
Mrna Levels ◽  
Prognostic Information ◽  
Clinical Patient ◽  
Quantitative Manner ◽  
L1 Protein

We aimed to assess if the discrepant prognostic information between Programmed Death Ligand 1 (PD-L1) protein versus mRNA expression in early breast cancer (BC) could be attributed to heterogeneity in its expression. PD-L1 protein and mRNA expression in BC tissue microarrays from two clinical patient cohorts were evaluated (105 patients; cohort 1: untreated; cohort 2: neoadjuvant chemotherapy-treated). Immunohistochemistry (IHC) with SP142, SP263 was performed. PD-L1 mRNA was evaluated using bulk gene expression and RNA-FISH RNAscope®, the latter scored in a semi-quantitative manner and combined with immunofluorescence (IF) staining for the simultaneous detection of PD-L1 protein expression. PD-L1 expression was assessed in cores as a whole and in two regions of interest (ROI) from the same core. The cell origin of PD-L1 expression was evaluated using multiplex fluorescent IHC. IHC PD-L1 expression between SP142 and SP263 was concordant in 86.7% of cores (p < 0.001). PD-L1 IF/IHC was weakly correlated with spatial mRNA expression (concordance 54.6–71.2%). PD-L1 was mostly expressed by lymphocytes intra-tumorally, while its stromal expression was mostly observed in macrophages. Our results demonstrate only moderate concordance between the various methods of assessing PD-L1 expression at the protein and mRNA levels, which may be attributed to both analytical performance and spatial heterogeneity.

scholarly journals Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer

2021 ◽  
Vol 28 (5) ◽  
pp. 4080-4092
Author(s):  
Takahiro Ichikawa ◽  
Masahiro Shibata ◽  
Takahiro Inaishi ◽  
Ikumi Soeda ◽  
Mitsuro Kanda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mrna Expression ◽  
Cell Lines ◽  
Mrna Levels ◽  
Pcr Array ◽  
Array Analysis ◽  
Expression Levels ◽  
Er Positive ◽  
Mrna Expression Levels

Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients’ clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. Results: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways.

scholarly journals Association between SPARC mRNA Expression, Prognosis and Response to Neoadjuvant Chemotherapy in Early Breast Cancer: A Pooled in-silico Analysis

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62451 ◽  
Author(s):  
Hatem A. Azim ◽  
Sandeep Singhal ◽  
Michail Ignatiadis ◽  
Christine Desmedt ◽  
Debora Fumagalli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Mrna Expression ◽  
Early Breast Cancer ◽  
In Silico ◽  
In Silico Analysis ◽  
Silico Analysis ◽  
Response To Neoadjuvant Chemotherapy

scholarly journals Expression of MTDH and IL-10 Is an Independent Predictor of Worse Prognosis in ER-Negative or PR-Negative Breast Cancer Patients

2020 ◽  
Vol 9 (10) ◽  
pp. 3153
Author(s):  
Pei-Yi Chu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
En-Pei Isabel Chiang
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Tissue Microarrays ◽  
Breast Cancer Patients ◽  
Worse Prognosis

(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.

Mucin-1 protein and mRNA expression in breast cancer: Predictive value for therapy response and survival after neoadjuvant chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 522-522
Author(s):  
Bruno Valentin Sinn ◽  
Gunter Von Minckwitz ◽  
Carsten Denkert ◽  
Holger Eidtmann ◽  
Silvia Darb-Esfahani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Predictive Value ◽  
Pathologic Complete Response ◽  
Therapy Response ◽  
Lower Probability ◽  
Muc1 Expression ◽  
Mrna Levels ◽  
Mucin 1 ◽  
Qrt Pcr

522 Background: Mucin-1 (MUC1) is expressed in normal epithelial cells and in breast cancer. Immunotherapeutic agents targeting MUC1 are currently tested in clinical trials. Methods: We evaluated the frequency of MUC1 expression by immunohistochemistry (IHC; n = 691) and quantitative RT-PCR (qRT-PCR; n = 286) in formalin-fixed paraffin-embedded (FFPE) pre-treatment biopsies from patients of the GeparTrio trial (NCT 00544765). mRNA levels were analyzed as a continuous variable, a distribution-based cut-off was chosen for IHC data. The predictive value for therapy response and survival after neoadjuvant anthracycline/taxane-based chemotherapy (CTX) was evaluated. Results: MUC1 was detectable by IHC in 95%. qRT-PCR covered a dynamic range of 3 orders of magnitude. IHC and mRNA data were correlated (p < 0.001). MUC1 was detected in higher quantities in HR+ tumors (p < 0.001), the lowest levels were found in HR-/HER2- tumors (p < 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (pCR) in the overall population (p < 0.001) and in HR+ (p = 0.004 and < 0.001), HER2- (p < 0.001) and HR+/HER2- tumors (p < 0.001). In multivariable logistic regression, MUC1 was independently predictive (high MUC1 protein: odds ratio (OR) 0.464, 95% CI 0.300 – 0.719, p = 0.001; MUC1 mRNA (per 20-dCT unit): OR 0.673, CI 0.546 – 0.829, p < 0.001). MUC1 protein and mRNA expression were associated with longer patient survival in the overall population (p = 0.03 and < 0.001) and in HER2- tumors (p = 0.005 and < 0.001). MUC1 mRNA was also prognostic in HR+ (p < 0.001) and HR+/HER2- tumors (p = 0.001). In multivariable analysis, protein and mRNA expression were independently prognostic (high MUC1 protein: hazard ratio (HR) 0.388, CI 0.166 – 0.907, p = 0.029; MUC1 mRNA per 20-dCT unit: HR 0.763, CI 0.595 – 0.909, p = 0.005). Conclusions: MUC1 is frequently expressed in breast cancer and detectable by IHC and qRT-PCR from FFPE tissue. Despite its association with HR+ status, it provides independent predictive information for therapy response and survival after neoadjuvant CTX. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker.

scholarly journals Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

2009 ◽  
Vol 16 (5) ◽  
pp. 1112-1121 ◽  
Author(s):  
So-Youn Jung ◽  
Wonshik Han ◽  
Jong Won Lee ◽  
Eunyoung Ko ◽  
Eunkyu Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Prognostic Information ◽  
Ki 67 ◽  
Online Risk ◽  
Risk Categories

scholarly journals Expression of genes modulated by epigallocatechin-3-gallate in breast cancer cells

2018 ◽  
Vol 64 (3) ◽  
pp. 31-37
Author(s):  
Anna Bogacz ◽  
Marlena Wolek ◽  
Bogna Juskowiak ◽  
Monika Karasiewicz ◽  
Adam Kamiński ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Expression Level ◽  
Mrna Levels ◽  
Mrna Expression Level

Summary Introduction: Breast cancer is the most common malignant cancer among women. Both drug resistance and metastasis are major problems in the treatment of breast cancer. Therefore, adjuvant therapy may improve patients’ survival and affect their quality of life. It is suggested that epigallocatechin gallate (EGCG) which is well known for its chemopreventive activity and acts on numerous molecular targets may inhibit the growth and metastasis of some cancers. Hence, discovering the metastatic molecular mechanisms for breast cancer may be useful for therapy. Objective: The aim of the study was to determine the effect of EGGC on the mRNA expression level of genes such as ZEB1, ABCB1, MDM2, TWIST1 and PTEN in MCF-7 breast cancer cells. Methods: MCF7/DOX were cultured in the presence of 0.2 μM DOX and EGCG (20-50 μM). The mRNA expression level was determined by real-time quantitative PCR using RealTime ready Custom Panel 96 kit. Results: Our results showed an important increase (about 2-fold for 20 μM EGCG + 0.2 μM DOX and 2.5-fold for 50 μM EGCG + 0.2 μM DOX, p<0.05) in ZEB1 expression levels. In case of ABCB1 gene lack of influence on the mRNA level was observed (p>0.05). We also observed significant decrease of ZEB1 expression in MCF7 cells with 20 μM and 50 μM EGCG (p<0.05). In addition, EGCG (20 μM) caused an increase of MDM2 and PTEN mRNA levels in almost 100% (p<0.05) and 40% (p>0.05), respectively. Lack of the influence of EGCG was noted for the TWIST1 gene expression. In case of MCF7/DOX we showed an increase of mRNA level of PTEN gene about 50% (p<0.05). Conclusions: These results suggest that EGCG may be potentially used in adjuvant therapy in the breast cancer treatment.

scholarly journals CHARACTERIZATION OF COLLAGEN (IV) MRNA IN CELL LINES OF BREAST CANCER

2015 ◽  
Vol 77 (25) ◽  
Author(s):  
Afzan Mat Yusof ◽  
Mardhiah Mohammad ◽  
Sharifah Norbaizura Syed Bahrom ◽  
Syahirah Kaja Mohideen ◽  
Ridhwan Roshdi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Collagen Iv ◽  
Breast Cancer Cell Lines ◽  
Mrna Levels

Breast cancer incidence rate has increased in the 5 recent years with 14% increases in mortality. The structural change in the collagen chain has led to alterations in the cancer cells. Various biological processes, such as differentiation or gene expression, are regulated through extracelullar matrix (ECM)[1]. The restructuring of the collagenous architecture in the hypoxic microenvironment may influence the invasive growth of the cancer cells. With the increased stress within the cell, the invasion of cancer cells into the ECM was triggered. This cell lines model would enable the exploration of the relationship between the extracellular matrices component and the tumor proliferation. The aim of this study is to characterize the collagen (IV) mRNA expression in the breast cancer cell.  Breast cancer (MCF7) cell lines were cultured and harvested upon confluent. The RNA was extracted from the cell lines and then the cDNA were synthesized. The collagen (IV) mRNA levels in breast cancer cell lines were measured using real time PCR and GAPDH was used as an internal control. The level of COL4A2 (IV) mRNA expression was higher compared with COL4A1 (IV) mRNA. The level of COL4A5 (IV) mRNA was reduced significantly in breast cancer cells lines. Overall, the expression of COL4A1-A6 (IV) was reduced. The reduced amount of collagen (IV) in breast cancer cell lines suggested that the collagen was restructured and this has triggered the tumor invasion into the ECM.

scholarly journals 217P Heterogeneity of PD-L1 expression at the protein and mRNA levels in early breast cancer

2020 ◽  
Vol 31 ◽  
pp. S328
Author(s):  
I. Zerdes ◽  
M. Stogiannitsi ◽  
J. Bergh ◽  
T. Hatschek ◽  
T. Foukakis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Mrna Levels

PD-1 protein and gene expression in early breast cancer: Prognostic implications.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 545-545
Author(s):  
Ioannis Zerdes ◽  
Alexios Matikas ◽  
John Lövrot ◽  
Emmanouil G. Sifakis ◽  
François Richard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Early Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cochrane Library ◽  
Study Cohort ◽  
Mrna Levels

545 Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear. Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistochemistry in tissue microarrays) and mRNA levels in a retrospective patient cohort of 586 patients treated for early BC in Stockholm, Sweden between 1997-2005, ii) systematic review and trial-level meta-analysis of studies published in Medline, Embase, Cochrane Library and Web of Science Core Collection libraries on the prognostic value of PD-1 IHC expression, and iii) pooled analysis of transcriptomic data from 39 publicly available datasets for the prognostic capacity of PD-1 gene expression. Univariate and multivariable Cox regression models were used. Results: In the retrospective study cohort, PD-1 protein was significantly associated with biologically high-risk characteristics. PD-1 protein, but not gene expression, was correlated with improved overall survival (OS) (adjusted HR = 0.73, 95% CI 0.55 – 0.96, p = 0.023 and adjusted HR = 0.88, 95% CI 0.68 – 1.13, p = 0.307, respectively). In the trial-level meta-analysis, 4736 entries were initially identified and 15 studies, including our original cohort, fulfilled the predefined eligibility criteria. PD-1 IHC expression was not prognostic in unselected patients. However, a significant correlation to improved disease-free survival was seen within the triple-negative subtype (pooled multivariate HR = 0.57, 95% CI 0.29 – 0.90, p = 0.02). In the pooled gene expression analysis, PD-1 gene expression was associated with improved OS in the entire population (adjusted HR = 0.89, 95% CI 0.80 – 0.99, p = 0.025) and in basal-like (adjusted HR = 0.77, 95% CI 0.63 – 0.95, p = 0.014) tumors. Conclusions: PD-1 expression at the RNA and protein levels represent promising prognostic factors, especially in the triple-negative and basal-like subtypes. Standardization and further validation are needed prior to clinical implementation.

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