Abstract LB-164: The association between p53, MDM2, and MDM2 isoform C protein expression and survival in a multiethnic population of breast cancer patients

(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.

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Genetic polymorphism of miRNA-196a and its target gene annexin-A1 expression based on ethnicity in Pakistani female breast cancer patients

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.35.6.1322 ◽

2019 ◽

Vol 35 (6) ◽

Author(s):

Amena Rahim ◽

Muhammad Afzal ◽

Abdul Khaliq Naveed

Keyword(s):

Breast Cancer ◽

Genetic Polymorphism ◽

Breast Cancer Risk ◽

Protein Expression ◽

Cancer Patients ◽

Target Gene ◽

Female Breast Cancer ◽

Annexin A1 ◽

Breast Cancer Patients ◽

Female Breast

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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Dj-1 Protein Expression in Intrinsic Subtype As a Predictor of Pathological Complete Remission After Neoadjuvant Chemotherapy in Breast Cancer Patients

Annals of Oncology ◽

10.1093/annonc/mdu326.38 ◽

2014 ◽

Vol 25 ◽

pp. iv69

Author(s):

H. Kaise ◽

T. Kawate ◽

K. Iwaya ◽

K. Yamada ◽

T. Ishikawa ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Complete Remission ◽

Protein Expression ◽

Cancer Patients ◽

Intrinsic Subtype ◽

Breast Cancer Patients ◽

Pathological Complete Remission

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Parathyroid hormone-related protein expression, in combination with nodal status, predicts bone metastasis and prognosis of breast cancer patients

Experimental and Therapeutic Medicine ◽

10.3892/etm.2012.521 ◽

2012 ◽

Vol 3 (6) ◽

pp. 963-968 ◽

Cited By ~ 14

Author(s):

KEIICHI TAKAGAKI ◽

TSUTOMU TAKASHIMA ◽

NAOYOSHI ONODA ◽

KENJI TEZUKA ◽

EIJI NODA ◽

...

Keyword(s):

Breast Cancer ◽

Parathyroid Hormone ◽

Bone Metastasis ◽

Protein Expression ◽

Cancer Patients ◽

Nodal Status ◽

Related Protein ◽

Breast Cancer Patients ◽

Parathyroid Hormone Related Protein

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High ERK Protein Expression Levels Correlate with Shorter Survival in Triple‐Negative Breast Cancer Patients

The Oncologist ◽

10.1634/theoncologist.2011-0377 ◽

2012 ◽

Vol 17 (6) ◽

pp. 766-774 ◽

Cited By ~ 52

Author(s):

Chandra Bartholomeusz ◽

Ana M. Gonzalez‐Angulo ◽

Ping Liu ◽

Naoki Hayashi ◽

Ana Lluch ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Patients ◽

Expression Levels

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

Journal of Clinical Medicine ◽

10.3390/jcm9103153 ◽

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.

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