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

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.

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

10.1101/346163 ◽

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.

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

Frontiers in Pharmacology ◽

10.3389/fphar.2020.584450 ◽

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.

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SIRT1 against breast cancer through downregulating Bcl-2 protein.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.34 ◽

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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Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer

Journal of Radiation Research ◽

10.1093/jrr/rraa083 ◽

2020 ◽

Vol 62 (1) ◽

pp. 110-118

Author(s):

Isabel Linares-Galiana ◽

Miguel Angel Berenguer-Frances ◽

Rut Cañas-Cortés ◽

Monica Pujol-Canadell ◽

Silvia Comas-Antón ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Single Dose ◽

Cancer Patients ◽

Antitumor Immunity ◽

Low Risk ◽

Intraoperative Radiation Therapy ◽

Breast Cancer Patients ◽

Intraoperative Radiation ◽

Risk Breast Cancer

Abstract A detailed understanding of the interactions and the best dose-fractionation scheme of radiation to maximize antitumor immunity have not been fully established. In this study, the effect on the host immune system of a single dose of 20 Gy through intraoperative radiation therapy (IORT) on the surgical bed in low-risk breast cancer patients undergoing conserving breast cancer has been assessed. Peripheral blood samples from 13 patients were collected preoperatively and at 48 h and 3 and 10 weeks after the administration of radiation. We performed a flow cytometry analysis for lymphocyte subpopulations, natural killer cells (NK), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs). We observed that the subpopulation of NK CD56+high CD16+ increased significantly at 3 weeks after IORT (0.30–0.42%, P < 0.001), while no changes were found in immunosuppressive profile, CD4+CD25+Foxp3+Helios+ Treg cells, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (Mo-MDSCs). A single dose of IORT may be an effective approach to improve antitumor immunity based on the increase in NK cells and the non-stimulation of immunosuppressive cells involved in immune escape. These findings support future combinations of IORT with immunotherapy, if they are confirmed in a large cohort of breast cancer patients.

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Is there a worthwhile value in personalizing radiation therapy for breast cancer patients? Time for a new paradigm in the older adult population

Expert Review of Precision Medicine and Drug Development ◽

10.1080/23808993.2021.1897463 ◽

2021 ◽

pp. 1-4

Author(s):

Viola Salvestrini ◽

Matteo Mariotti ◽

Marco Banini ◽

Carlotta Becherini ◽

Luca Visani ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Cancer Patients ◽

Older Adult ◽

Adult Population ◽

Breast Cancer Patients ◽

New Paradigm ◽

Older Adult Population

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MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

International Journal of Molecular Sciences ◽

10.3390/ijms22105382 ◽

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.

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Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽

10.3390/cancers13010002 ◽

2020 ◽

Vol 13 (1) ◽

pp. 2

Author(s):

Lee D. Gibbs ◽

Kelsey Mansheim ◽

Sayantan Maji ◽

Rajesh Nandy ◽

Cheryl M. Lewis ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Significance ◽

Cell Lines ◽

Breast Cancer Subtypes ◽

Enzyme Linked Immunosorbent Assay ◽

Breast Cancer Patients ◽

Serum Samples ◽

Cancer Subtypes ◽

Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

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