Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients

2010 ◽  
Vol 126 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Maria Aparecida Nagai ◽  
Renê Gerhard ◽  
José Humberto T. G. Fregnani ◽  
Suely Nonogaki ◽  
Regina Barbosa Rierger ◽  
...  
2021 ◽  
Author(s):  
Jun Wang ◽  
Xuebing Zhan ◽  
Qian Luo ◽  
Yunshu Kuang ◽  
Xiao Liang ◽  
...  

Abstract Background: Breast cancer is one of the most common tumors for women worldwide. Thrombospondins (THBSs) are reported to play important roles in various cellular processes and are involved in the occurrence and development of human cancers. However, the expression and prognostic value of THBSs family in breast cancer remain unclear.Methods: In this study, we examined the genes and protein expression levels of THBSs and their prognostic value by synthesizing several mainstream databases, including Oncomine, Human Protein Atlas (HPA), UALCAN, and KM Plotter. We also analyzed THBS interaction networks, genetic alterations, functional enrichment, and drug sensitivity with several publicly accessible databases, including GEPIA, GeneMANIA, STRING, cBioPortal, Metascape and NCI-60 database.Results: The results showed that the mRNA expression levels of THBS1, THBS2, THBS3, and THBS5 in breast cancer tissues were significantly higher than in normal tissues. The mRNA expression levels of THBS4 were different in different subtypes of breast cancer, and the protein expression levels of THBS1, THBS2, and THBS4 in breast cancer tissues were higher than in normal breast tissues. Survival analysis showed that breast cancer patients with high THBS1 gene expression showed worse overall survival (OS), relapse-free survival (RFS), and post-progression survival (PPS), and breast cancer patients with high THBS2 gene expression also showed worse RFS. Conversely, lower THBS3 levels predicted worse RFS, and lower THBS4 levels predicted worse OS, RFS, and distant metastasis-free survival (DMFS). Conclusions: These results suggest that THBSs may be potential biomarkers for breast cancer.


2019 ◽  
Vol 20 (6) ◽  
pp. 941-947 ◽  
Author(s):  
Ziping Wu ◽  
Lei Zhang ◽  
Jing Peng ◽  
Shuguang Xu ◽  
Liheng Zhou ◽  
...  

2021 ◽  
Vol 22 (10) ◽  
pp. 5382
Author(s):  
Pei-Yi Chu ◽  
Hsing-Ju Wu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
...  

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.


2011 ◽  
Vol 47 ◽  
pp. S333
Author(s):  
M. Riaz ◽  
A. Sieuwerts ◽  
M. Look ◽  
M. Smid ◽  
J. Foekens ◽  
...  

2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  

Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.


2019 ◽  
Vol 35 (6) ◽  
Author(s):  
Amena Rahim ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed

Objective: To evaluate the association of miR-196a rs11614913 C/T genetic variation and its target gene annexin A1 mRNA expression with breast cancer risk in Pakistani female ethnicities. Methods: This case control study, conducted from March 2017 to November 2018 included 295 breast cancer patients, 295 controls of three Pakistani ethnicities and archived 100 samples of cohort group for genotyping and expression profiling. Genotyping of miR-196a (rs11614913 C/T) was done by ARMS PCR technique. Annexin-A1 (ANXA1) mRNA expression was measured with qRT-PCR and detection of protein expression of ANXA1 was done by immunohistochemistry. Results: CC homozygous genotype of miR-196a rs11614913 was present in 81.4% of cases and 73.9% controls. C/T polymorphism was found to be significantly associated with decrease risk of breast cancer (OR=0.25 (0.11- 0.58, p <0.05). Similar trend was seen with the minor T allele (OR=0.55 (0.39-0.77, p <0.05, and both dominant and recessive models (OR=0.64; p=0.02 and OR=0.26, p=0.00). In the KPK ethnic group significant decrease association with breast cancer risk was observed (OR= 0.22 (0.09-0.53, p < 0.05). Immunohistochemical staining showed loss of ANXA1 protein expression in 72 samples, and significant association was observed with pathological type p=0. 00 and triple negative receptor status p=0.03 and with genotypes of miR-196a p=0.00. Increase relative expression of 2.81± .88 by qPCR analysis of ANXA1 mRNA was noted with TT genotype. Conclusions: Our results demonstrate that miR-196a rs11614913 C/T polymorphism is associated with a decreased risk and loss of protein expression in breast cancer in the Pakistani population. doi: https://doi.org/10.12669/pjms.35.6.1322 How to cite this:Rahim A, Afzal M, Naveed AK. Genetic polymorphism of miRNA-196a and its target gene annexin-A1 expression based on ethnicity in Pakistani female breast cancer patients. Pak J Med Sci. 2019;35(6):1598-1604. doi: https://doi.org/10.12669/pjms.35.6.1322 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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