scholarly journals IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Hua ◽  
Zhi-Qing Long ◽  
Ling Guo ◽  
Wen Wen ◽  
Xin Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Subgroup Analysis ◽  
Poor Prognosis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Tumor Tissues

Background: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest identified member of the IQGAP family, may act as a crucial factor in cancer development and progression; however, its clinical value in breast cancer remains unestablished. We explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer.Methods: IQGAP3 mRNA and protein levels were detected in breast cancer cell lines and tumor tissues by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was also evaluated immunohistochemically in archived paraffin-embedded specimens from 257 breast cancer patients, and the associations between IQGAP3 expression level, clinical characteristics, and prognosis were analyzed. We assessed the relationship between IQGAP3 expression and sensitivity to radiation therapy which was determined by subgroup analysis.Results: IQGAP3 was significantly upregulated in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to controls. Additionally, high levels of IQGAP3 expression were detected in 110/257 (42.8%) of archived paraffin-embedded breast cancer specimens. High IQGAP3 expression level was significantly related to clinical stage (p = 0.001), T category (p = 0.002), N category (p = 0.001), locoregional recurrence (p = 0.002), distant metastasis (p = 0.001), and vital status (p = 0.001). Univariate and multivariate statistical analysis showed that IQGAP3 expression was an independent prognostic factor among all 257 breast cancer patients in our cohort (p = 0.003, p = 0.001). Subgroup analysis revealed IQGAP3 expression correlated with radioresistance and was also an independent predictor of radiotherapy outcome.Conclusion: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radioresistance in breast cancer. Therefore, IQGAP3 may be a reliable prognostic biomarker in breast cancer and could be used to identify patients who may benefit from radiotherapy.

scholarly journals IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

2018 ◽  
Author(s):  
Xin Hua ◽  
Zhi-Qing Long ◽  
Wen-Wen Zhang ◽  
Chao Lin ◽  
Xiao-Qing Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Protein Expression ◽  
Cancer Patients ◽  
Subgroup Analysis ◽  
Poor Prognosis ◽  
Therapy Resistance ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Tumor Tissues

AbstractBackground: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest found protein of IQGAP family, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer. Methods: IQGAP3 levels in breast cancer cell lines and tumor tissues were detected by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was evaluated immunohistochemically in specimens (archived paraffin embedded) of 257 breast cancer patients. We also analyze the association between IQGAP3 expression and the clinical characters and prognosis. The relationship between IQGAP3 expression and sensitivity to radiation therapy was determined by subgroup analysis. Results: There was significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to the normal ones. In addition, 110/257 (42.8%) of archived paraffin embedded breast cancer specimens had high protein expression of IQGAP3. High expression of IQGAP3 was significantly related to clinical stage (P=0.001), T category (P=0.002), N category (P=0.001), locoregional recurrence(P=0.002), distant metastasis (P=0.001), and vital status (P=0.001). Univariate and multivariate statistical analysis showed that IQGAP3 was an independent prognostic factor of the whole cohort breast cancer patients (P=0.003, P=0.001). Subgroup analysis revealed IQGAP3 expression correlates with radiation therapy resistance and was also an independent predictor for radiation therapy outcome. Conclusions: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radiation therapy resistance in breast cancer. In addition, IQGAP3 may be a reliable novel biomarker to provide personalized prognostication and identify patients who can profit from more aggressive RT regimen for improving the survival of breast cancer patients.

IQ Motif-Containing GTPase-Activating Protein 3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

2019 ◽  
Vol 11 (5) ◽  
pp. 653-663
Author(s):  
Xin Hua ◽  
Qihang Yan ◽  
Zhiqing Long ◽  
Xin Huang ◽  
Jiapeng Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Subgroup Analysis ◽  
Therapy Resistance ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Gtpase Activating Protein ◽  
Iq Motif ◽  
Tumor Tissues

IQ motif-containing GTPase-activating protein 3 (IQGAP3), the latest found IQGAP family protein, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between the IQGAP3 expression profile and clinicopathological features in breast cancer. IQGAP3 levels in breast cancer cell lines and tumor tissues were detected through real-time PCR and western blotting. We evaluated IQGAP3 expression in archived paraffin-embedded tissue specimens of 257 breast cancer patients, and determined the relationship between IQGAP3 expression and sensitivity to radiation therapy (RT), using subgroup analysis. We also analyzed the association between IQGAP3 expression and the clinical characters and prognosis of breast cancer. There was a significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both mRNA and protein levels. In addition, 42.8% of the breast cancer specimens had high expression of IQGAP3, which was significantly related to clinical stage (P = 0.001), T category (P = 0.002), N category (P = 0.001), locoregional recurrence (P = 0.002), distant metastasis (P = 0.001), and vital status (P = 0.001). Univariate and multivariate statistical analyses showed that IQGAP3 is an independent prognostic factor for all the breast cancer patients (P = 0.003, P = 0.001). Subgroup analysis revealed that IQGAP3 expression is correlated with radiation therapy resistance and is an independent predictor for radiation therapy outcome. Our findings suggest that IQGAP3 may be a reliable novel biomarker to provide personalized prognosis and identify patients who can profit from a more aggressive RT regimen for improving breast cancer patient survival.

scholarly journals MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5382
Author(s):  
Pei-Yi Chu ◽  
Hsing-Ju Wu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Protein Expression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Expression Ratio

(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.

scholarly journals Increased Soluble CrkL in Serum of Breast Cancer Patients Is Associated with Advanced Disease

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 961 ◽  
Author(s):  
Srimeenakshi Srinivasan ◽  
Biana Godin
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Advanced Disease ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Human Breast

Over-expression of Crk-like protein (CrkL), an intracellular adaptor protein, in breast cancer biopsies has been linked to poor prognosis. CrkL can be secreted from cancer cells binding to β1 integrin on the cell membrane. In this study, we evaluated, for the first time, the levels of soluble CrkL in serum of breast cancer patients. Expression of CrkL and secreted fractions from human breast cancer cell lines and clinical patient samples were assessed by immunohistochemistry and Enzyme Linked Immuno-Sorbent Assay (ELISA). CrkL levels in tissues and sera of patients with different disease stages were compared and statistically analyzed by Chi-square test and Student’s t-test. Culture media from human breast cancer cell lines SUM159, MDA-MB231, and MCF7 showed over a 21-, 15-, and 11-fold higher concentration of soluble CrkL as compared to normal breast epithelium cell line MCF10A. Expression of CrkL was elevated in 85% of breast tumor tissue sections. Serum levels of CrkL were significantly higher in breast cancer patients than in healthy donors. All patients with metastatic disease had significantly elevated concentration of soluble CrkL in the serum with on average three-fold increase from the baseline. The data suggest that soluble fraction of CrkL can be further evaluated as a serum biomarker for advanced disease in breast cancer patients.

scholarly journals MMP1 and MMP11 expression in Peripheral Blood Mononuclear Cells upon their interaction with Breast Cancer Cells and Fibroblasts

2020 ◽  
Author(s):  
Noemi Eiro ◽  
Sandra Cid ◽  
Nuria Aguado ◽  
María Fraile ◽  
Jorge Rubén Cabrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Inflammatory Genes

Abstract Background: Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the Peripheral Blood Mononuclear Cells (PBMC) from breast cancer patients. Here, we investigated the expression of MMP1 and MMP11 in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and Cancer-Associated Fibroblasts (CAF). Finally, we measured the impact of PBMC in proinflammatory genes expression in normal fibroblast and CAF.Results: Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n=54) and control (n=28), and expression of IL1A, IL6, IL17, IFNβ and NFB in breast cancer cell lines (MCF-7 and MDA-MB-231), CAF and in Normal Fibroblasts (NF) were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a group of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, we present evidence of increased gene expression of MMP1 and MMP11 in PBMC after co-culture with breast cancer cell lines, NF or CAF. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC.Conclusions: We have observed that MMPs expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by control or breast cancer PBMC. These findings confirm the importance of the interaction and communication between stromal cells and suggest that PBMC would play a role to promote an aggressive tumor behavior.

SIRT1 against breast cancer through downregulating Bcl-2 protein.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 34-34
Author(s):  
Dar-Ren Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Tumor Promoter ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Class Iii ◽  
Tumor Tissues ◽  
Mcf 7

34 Background: SIRT1, a member of the class III histone deacetylase (HDAC) family, is the mammalian orthologue of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival due to its ability to deacetylate both histone and numerous non-histone substrates. The deacetylase function of SIRT1 has been suggested as playing a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective down- and up-regulation in various cancers. The aim of the present study was to simultaneously evaluate the expression levels of SIRT1 and Ki67, the index of cellular proliferation, in normal and tumor tissues of the breast from 27 breast cancer patients and to determine the role of SIRT1 in breast tumorigenesis. Methods: A total of 27 breast cancer patients were included. Tumor tissues and matched normal breast tissues were immediately frozen after collection between 2007 and 2008. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied for analyses of patients’ specimens. Cell proliferation assay, cell cycle analysis and Western blotting were used to investigate the effects of sirtinol on the human breast cancer lines MCF-7 and MDA-MB-231 cells. Results: Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. In addition, our results showed that inhibition of SIRT1 induces anti-cell growth in both MCF-7 (ER-positive, non-invasive) and MDA-MB-231 (ER-negative, invasive) breast cancer cell lines, especially in MDA-MB-231 cells. The levels of pro-survival protein Bcl-2 were dramatically decreased in both breast cell lines following sirtinol treatment. Conclusions: Our present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.

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