[Show abstract][Hide abstract] ABSTRACT: Objective:
To explore the relationship between TβRII [type II TGFβ (transforming growth factor β) receptor] expression and clinicopathological characteristics, and to evaluate the prognostic significance of TβRII expression in breast cancer.
Clinicopathological data and prognostic information of 108 patients with histologically confirmed breast cancer who were surgically treated at China Medical University between January 2007 and September 2008 were reviewed and the association between the clinicopathological characteristics and TβRII expression was analyzed by chi-square test and multivariate analysis. The expression of TβRII was assessed by immunohistochemistry.
Of the 108 patients, 60 cases were TβRII positive and 48 cases were negative. There was no significant association between TβRII expression of the patients older than 40 years and that of the younger than 40 years (56.0% vs 50.0%; P = 0.742). The TβRII expression rate was significantly increased in patients with lymph node metastasis compared to those without lymph node metastasis (67.40% vs 46.8%; P = 0.033). Statistically significant relationships were found between increasing tumor clinical stage and high TβRII expression (P = 0.011). TβRII expression was not associated with the expression of ER(estrogen receptor)、PR, (progesterone receptor)、Her-2 (human epidermal growth factor receptor 2) (P = 0.925,P = 0.861, and P = 0.840, respectively). Patients with high TβRII expression showed poorer 5-year disease-free survival (DFS) compared to those with low expression (66.7% vs 45.6%; P = 0.028) by univariate analysis. Survival analysis demonstrated that TβRII was associated with poor DFS (P = 0.011). Subgroup analysis revealed that TβRII expression was associated with shorter DFS in patients with lymph node metastasis, ER-positive, PR-positive or Her-2-negative tumors (P = 0.006, P = 0.016, P = 0.022, and P = 0.033, respectively). Cox regression analysis revealed that high TβRII expression was related to poor 5-year DFS, and it was an independent factor for predicting the poor outcome for breast cancer patients (P = 0.016).
High levels of TβRII expression were associated with lymph node metastasis, increasing tumor clinical stage, and poorer 5-year DFS in patients with breast cancer. TβRII may be a potential prognostic marker for breast cancer.
PLoS ONE 11/2015; 10(11):e0141412. DOI:10.1371/journal.pone.0141412 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: WT1 +KTS and -KTS isoforms only differ in three amino acids in protein sequence but show significant functional difference. The +/-KTS isoforms were generated by alternative usage of two adjacent 5' splice sites at RNA level, however, how these two isoforms are regulated is still elusive. Here we report the identification of an intronic pyrimidine-rich sequence that is critical for the ratio of +/-KTS isoforms, deletion or partial replacement of the sequence led to full/significant shift to -KTS isoform. To identify trans-factors that can regulate +/-KTS isoforms via the binding to the element, we performed RNP assembly using in vitro transcribed RNA with or without the pyrimidine-rich sequence. Mass spectrometry analysis of purified RNPs showed that the element associated with many splicing factors. Co-transfection of these factors with WT1 reporter revealed that HuR promoted the production of -KTS isoform at the reporter level. RNA immuno-precipitation experiment indicated that HuR interacted with the pyrimidine-rich element in WT1 intron 9. We further presented evidence that transient or stable over-expression of HuR led to enhanced expression of endogenous -KTS isoform. Moreover, knockdown of HuR resulted in decreased expression of endogenous -KTS isoform in 293T, SW620, SNU-387 and AGS cell lines. Together, these data indicate that HuR binds to the pyrimidine-rich sequence and antagonize its effect in regulating WT1 +/-KTS isoforms.
[Show abstract][Hide abstract] ABSTRACT: We investigated the miRNA profiles of breast cancer stem cells (CSCs) and non-CSC tumor cells by miRNA microarray and determined the effect of altered miR-1 expression on proliferation and migration of breast CSCs. The potential targets of miR-1 in the Wnt/β-catenin signaling were characterized by bioinformatics analysis and luciferase assay. We found that 14 miRNAs were up-regulated and 13 were down-regulated in the ESA+CD44+CD24-lineage- CSCs, related to ESA+CD44-CD24+lineage- non-CSC tumor cells. The miR-1 expression was associated inversely with aggressiveness of breast cancers. Furthermore, enhanced miR-1 expression decreased the percentages of SKBR3/CSCs and miR-1 inhibition increased the percentages of MCF-7/CSCs. Enhanced miR-1 expression significantly reduced the Frizzled 7 and Tankyrase-2 (TNKS2)-regulated luciferase activity in 293T cells and decreased Frizzled 7, TNKS2, c-Myc, octamer-binding transcription factor 4 (Oct4) and Nanog expression and the ratios of nuclear to cytoplasmic β-catenin as well as β-catenin-dependent luciferase activity in breast CSCs in vitro. miR-1 inhibited proliferation, migration and wound healing of breast CSCs in vitro. Enhanced miR-1 expression inhibited the growth of implanted MCF-7/CSCs while miR-1 inhibition promoted the growth of implanted MCF-7/CSCs in vivo. Our data indicate that miR-1 down-regulates breast CSC stemness, proliferation and migration by targeting the Frizzled 7 and TNKS2 to inhibit the Wnt/β-catenin signaling.
[Show abstract][Hide abstract] ABSTRACT: To clarify the composition of wound fluid (WF) and investigate the impact of WF on breast cancer cell lines.
The proliferation and migration of WF-treated breast cancer cells MDA-MB-231 and MCF-7 were assessed with colony formation test, MTT cell proliferation test and scratch wound test. The quantitative profiles of WF were analyzed using Bio-Plex Pro kits.
The proliferation and migration of WF-treated breast cancer cells were significantly higher than that of untreated cells. Fifteen cytokines, 29 chemokines and 9 matrix metalloproteinases (MMPs) were assessed in WF. The concentrations of these factors were influenced by post-surgery days, neoadjuvant chemotherapy (NAC), TNM stage, pathological type and molecular subtype. The WF harvested from patients underwent NAC showed significant higher profiles of interleukin-1β (IL-1β), IL-4, IL-6, IL-17F, IL-21, IL-23, IL-25, IL-31, Interferon γ (IFNγ), CD40 ligand (CD40L), tumor necrosis factor α (TNFα), CXCL1, CXCL2, CXCL5, CCL3, CCL7 and CCL20.
Surgery-induced WF promotes the proliferation and migration of breast cancer cells. The composition of WF is influenced by various clinical features and provides potential therapeutic targets to control local recurrence and tumor progression.
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinicopathological significance of the expression of fibrous sheath interacting protein 1 (FSIP1) in breast cancer, serum samples, and wound fluid from patients with breast cancer.
Wound fluid and serum samples from female patients with primary breast cancer, recurrent and metastatic breast cancer, and benign tumors were analyzed for FSIP1 expression using ELISA. 286 paraffin-embedded surgical specimens from breast cancer patients with at least 5 years of follow-up were included for FSIP1 expression assay using immunohistochemistry.
Expression of FSIP1 protein was significantly higher in breast cancer tissues compared to tumor-adjacent tissues (p = 0.001). Strong correlation was observed between FSIP1 expression and human epidermal growth factor receptor 2 (Her-2) or Ki67 expression in breast cancer (p = 0.027 and 0.002, respectively). Similarly, serum level of FSIP1 was higher in patients with recurrent and metastatic breast cancer compared to that of primary breast cancer (7, 713 ± 3, 065 vs. 4, 713 ± 3, 065 pg/ml, p = 0.003). Finally, patients with high FSIP1 expression showed a worse post-operative disease-specific survival (p = 0.024).
FSIP1 may play an important role in the tumorigenesis and invasion of breast cancer and is a potential biomarker for breast cancer diagnosis or prognosis.
[Show abstract][Hide abstract] ABSTRACT: Small proline-rich repeat protein 1A (SPRR1A) is a marker for terminal squamous cell differentiation. Previous studies showed that SPRR1A expression increases in squamous cell carcinoma of the skin, but decreases in esophageal squamous cell carcinoma. This study focuses on the expression of SPRR1A protein in breast cancers (BCs) in China. A total of 111 patients with histologically confirmed BC, who underwent radical surgery between January 2006 and September 2007 in China Medical University, were enrolled. The relationship between SPRR1A expression and clinicopathological factors as well as BC prognoses was also determined. Overall, SPRR1A expression was detected in more than half of the BC specimens by immunohistochemistry (56/111, 53.8 %), but there was no significant difference between age groups (≥50 vs. <50 years) in terms of SPRR1A expression (P = 0.915), as well as no differences between SPRR1A expression and the clinical stage (0-I vs. II-III) or nodal status (P = 0.234 and 0.632, respectively). Moreover, human epidermal growth factor receptor 2 overexpression was not correlated with SPRR1A expression, whereas Ki67 was associated with SPRR1A expression (P = 0.155 and 0.028, respectively). Interestingly, SPRR1A expression was significantly associated with progesterone receptor-positive (P = 0.010) rather than estrogen receptor-positive (0.778) BCs. The 5-year survival rate in patients did not differ with the presence or absence of SPRR1A expression (P = 0.753), whereas the combination of SPRR1A expression, progesterone receptor status, and menopausal status allowed identification of a subgroup of BC patients with a good long-term prognosis. Thus, the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups.
[Show abstract][Hide abstract] ABSTRACT: Oct-4 and Nanog in regulating the epithelial-mesenchymal transition (EMT) and metastasis of breast cancer has not been clarified. We found that both Oct-4 and Nanog expression were significantly associated with tumor pathology and poor prognosis in 126 breast cancer patients. Characterization of CD44+CD24-Cancer stem cell(CSC) derived from breast cancer cells indicated that CSC rapidly formed mammospheres and had potent tumorigenicity in vivo. Furthermore, TGF-β up-regulated the expression of Oct-4, Nanog, N-cadherin, vimentin, Slug, and Snail, but down-regulated E-cadherin and cytokeratin 18 expression, demonstrating that CSC underwent EMT. Knockdown of both Oct-4 and Nanog expression inhibited spontaneous changes in the expression of EMT-related genes, while induction of both Oct-4 and Nanog over-expression enhanced spontaneous changes in the expression of EMT-related genes in CSC. However, perturbing alternation of Oct-4 and Nanog expression also modulated TGF-β-induced EMT-related gene expression in CSC. Induction of Oct-4 and Nanog over-expression enhanced the invasiveness of CSC, but knockdown of both Oct-4 and Nanog inhibited the migration of CSC in vitro. Our data suggest that both Oct-4 and Nanog may serve as biomarkers for evaluating breast cancer prognosis. Our findings indicate that Oct-4 and Nanog positively regulate the EMT process, contributing to breast cancer metastasis.
[Show abstract][Hide abstract] ABSTRACT: Galectin-3 has a relatively high level of expression in triple-negative breast cancers and is a potential marker for this disease. However, the clinical and prognostic implications of galectin-3 expression in breast cancer remain unclear. We examined mastectomy specimens from 1086 breast cancer cases and matching, adjacent non-cancerous tissues using immunohistochemistry. Overall, triple-negative breast cancers expressed galectin-3 more strongly than did other breast cancers types (63.59% vs 21.36%, P = 0.001). Galectin-3 expression was not found to be an independent prognostic factor for breast cancer by Cox regression analysis, but was associated with chemotherapeutic resistance. Apoptosis was only weakly induced by arsenic trioxide (ATO) treatment in galectin-3-positive breast cancer cells (MDA-MB-231 and MCF-7), although ATO treatment up-regulated galectin-3 expression. Knockdown of galectin-3 in MDA-MB-231 cells sensitized them to killing by ATO. These findings support a possible role for galectin-3 as a marker for triple-negative breast cancer progression and as a therapeutic target in combination with ATO treatment, although the mechanisms that underlie this synergy require further investigation.
PLoS ONE 09/2014; 9(9):e103482. DOI:10.1371/journal.pone.0103482 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionWe investigated Nestin expression in triple-negative breast cancer and examined how the modulation of Nestin expression affects cell cycle progression, survival, invasion and regulatory signaling in breast cancer stem cells (CSC) in vitro.Methods
Nestin expression in 150 triple-negative breast cancer specimens were examined by immunohistochemistry. The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin-silenced breast CSC were investigated by flow cytometry and transwell assays. The relative levels of expression of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related molecules were determined by western blotting.ResultsNestin expression was significantly associated with poor survival in patients with triple-negative breast cancer (p¿=¿0.01). Nestinhigh breast CSC rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC, efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45% versus 8.29% in controls). Nestin silencing also inhibited breast CSC invasiveness, and was associated with significantly upregulated E-cadherin, while N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was downregulated (p¿<¿0.05 for all). Nestin silencing also upregulated Axin, glycogen synthase kinase-3 beta (GSK-3ß), adenomatous polyposis coli (APC), and peroxisome proliferator-activated receptor alpha (PPARa), and downregulated ß-catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/ß-catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while inhibition of GSK-3ß promoted the mammosphere formation in Nestinlow CSC (p¿<¿0.05 for all).Conclusions
Our data indicates that Nestin positively regulates the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/ß-catenin activation.
Breast cancer research: BCR 07/2014; 16(4):408. DOI:10.1186/s13058-014-0408-8 · 5.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Curative resection is the treatment of choice for gastric cancer, but it is unclear whether gastrectomy should also include splenectomy. We retrospectively analyzed long-term survival in patients in our hospital who underwent gastrectomy plus splenectomy (G + S) or gastrectomy alone (G-A) for gastric cancer.
We identified 214 patients who underwent surgery with curative intent between 1980 and 2003. Of these, 100 underwent G + S, and 114 underwent G-A. The primary endpoint was 5-year overall survival (OS).
Median follow-up was 18 months in patients who underwent G + S, and 26.5 months in patients who underwent G-A. The 5-year OS rate was significantly higher in patients who underwent G-A (33.8%; 95% CI 24.2 to 43.4%) than in those who underwent G + S (28.8%; 95% CI 19.6 to 38.0%) (log-rank test, P = 0.013).
Splenectomy does not benefit patients undergoing gastrectomy for gastric cancer. Routine splenectomy should be abandoned in patients undergoing radical resections for gastric cancer.
World Journal of Surgical Oncology 06/2014; 12(1):193. DOI:10.1186/1477-7819-12-193 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Certain markers have been identified over the last 10 years that facilitate the prediction of a patient’s prognosis; these markers have been proposed to be useful for risk stratification of lymphoma patients and for the development of specific therapeutic strategies. In the present study, we assessed the potential prognostic value of SPRR1A expression in 967 patients with diffuse large B-cell lymphomas.
All patients were enrolled between 2001 and 2007 (median follow-up, 53.3 months) in the Second Hospital of Dalian Medical University, First Hospital of China Medical University, and Liaoning Cancer Hospital. Immunohistochemical analysis was used to evaluate the expression of SPRR1A. Survival was analyzed using the Kaplan–Meier method. Multivariate analysis was conducted to adjust the effect of SPRR1A expression for potential, well-known, independent prognostic factors.
Of the 967 patients examined, SPRR1A expression was detected in 305 (31.54%) patients on immunohistochemical analysis. The 5-year survival rate was significantly lower in patients with SPRR1A expression than in those without (26.9% vs. 53.2%, P < 0.001). Multivariate analysis identified SPRR1A expression as an independent predictor of survival in addition to lactate dehydrogenase level, clinical stage, and histologic subtype.
SPRR1A expression may be useful as a prognostic factor for diffuse large B-cell lymphoma.
BMC Cancer 05/2014; 14(1):333. DOI:10.1186/1471-2407-14-333 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
We investigated the expression status of AGBL2 and its inhibitor latexin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer.
CD44+/CD24- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. AGBL2 expression status was detected in CSC and 126 breast cancer specimens by western blot and immunohistochemistry staining. The relationship between the AGBL2 protein and clinicopathological parameters and prognosis was subsequently determined.
As a result, CSC are more likely to generate new tumors in mice and cell microspheres that are deficient in non-obese diabetic/severe combined immunodeficiency mice (NOD/SCID) compared to the control group. The AGBL2 protein was expressed higher in CSC induced to epithelial to mesenchymal transition (EMT) when compared to the control cells, and was found to be related to CSC chemotherapy resistance. After Spearman regression correlation analysis, AGBL2 was observed to be related to clinical stage, histological stage, and lymph node metastasis. In the Cox regression test, the AGBL2 protein was detected as an independent prognostic factor. Through immunoprecipitation, AGBL2 and latexin could form immune complexes.
These results demonstrate that AGBL2 is a latexin-interacting protein that regulates the tubulin tyrosination cycle and is a potential target for intervention.
World Journal of Surgical Oncology 05/2014; 12(1):142. DOI:10.1186/1477-7819-12-142 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this case study and review, we present a case of a primary small-cell neuroendocrine carcinoma (SCNC) of the male breast. Primary SCNC of the breast is a rare tumor with less than 30 cases reported in the literature. Most cases are found in women. Another exceptional point is that human epidermal growth factor receptor-2 (Her-2) immunoreactivity was positive in our recent case, which differed to previous reports detailing SCNC in women. We have no evidence to demonstrate the differences between treatment and prognoses for males and females, because we do not have sufficient cases to undertake an evidence-based investigation. We provide this rare case history; review the literature on SCNC of the breast; and discuss detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, surgical and adjuvant treatment, and prognosis.
OncoTargets and Therapy 05/2014; 7:663-6. DOI:10.2147/OTT.S60782 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is well-established that triple-negative breast cancer (TNBC) is a subtype of breast cancer, characterized by a poor prognosis and aggressive biological behavior. However, the available relevant data on TNBC in non-Western populations are limited. In order to analyze the clinicopathological and molecular biological characteristics and observe survival and prognostic factors, 972 breast cancer patients (156 of whom had TNBC) who received treatment at the First Affiliated Hospital of Medical School of Xi'an Jiaotong University and the First Hospital of China Medical University, between January, 2004 and January, 2007 were retrospectively evaluated. In the univariate analysis, tumor size, TNM stage, axillary lymph node status and recurrence or metastasis were identified as prognostic factors for 7-year disease-free survival (DFS) and overall survival (OS). Our multivariate Cox's regression analysis demonstrated that tumor size and axillary lymph node status were significant prognostic factors for 7-year DFS and OS. Notably, tumor subgroup (TNBC vs. non-TNBC) was a significant prognostic factor associated with 7-year DFS and OS in breast cancer. It was suggested that TNBC exhibited a worse 7-year survival compared with that in non-TNBC patients, most likely due to its more aggressive behavior and insensitivity to specific therapy.
Molecular and Clinical Oncology 03/2014; 2(2):245-251. DOI:10.3892/mco.2013.230
[Show abstract][Hide abstract] ABSTRACT: Interleukin 27 (IL-27), belonging to the IL-12 family, exerts a critical role in immune regulation of infection, autoimmunity, and tumor. In this study, we aimed to investigate the roles of IL-27 and vascular endothelial growth factor (VEGF) in breast cancer.
The serum levels of IL-27 and VEGF in 150 patients with breast cancer and 90 control subjects were measured by an enzyme-linked immunosorbent assay. Estrogen receptor, progesterone receptor, and human epithelial growth factor receptor 2 were measured by immunohistochemistry. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were also recorded.
The serum levels of IL-27 and VEGF were significantly greater in breast cancer patients than in the control group. In addition, there was a significant correlation between IL-27 and VEGF, and serum IL-27 and VEGF levels were associated with the clinical stage of breast cancer. Moreover, the serum levels of IL-27 were especially elevated in breast cancer patients who were estrogen receptor-positive and progesterone receptor-positive. Furthermore, the serum levels of IL-27 and VEGF decreased after patients with breast cancer had modified radical mastectomy.
Interleukin 27 may be a new prognostic biomarker of breast cancer and a promising target to limit both angiogenesis and tumor growth.
Journal of Investigative Medicine 01/2014; 62(3). DOI:10.231/JIM.0000000000000046 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to investigate the relationship between nestin expression and clinicopathological characteristics, immunohistochemical markers and to determine the prognostic impact of nestin expression in breast cancer so as to lay a foundation for the treatment of breast cancer. A total of 109 patients who were histologically diagnosed with breast cancer and underwent radical operations from January 2006 to September 2007 in China Medical University were enrolled in the study. Nestin protein expression was evaluated by immunohistochemistry. The relationship between nestin and other parameters was analyzed by using chi-square test and Fisher's exact test. Nestin expression was observed in 37.6 % (41/109) of cases. There were no significant differences between the age of >40 and ≤40 years group in terms of nestin expression (39.8 vs 18.2 %; P = 0.161). The rate of nestin expression between those with and without lymph node metastasis was not significantly different (X (2) = 0.086; P = 0.769). The 5-year survival rates of the patients with nestin expression and those without were 34.1 % (14/41) and 55.9 % (38/68), respectively (P = 0.028). Overall, triple-negative breast cancers had higher expression rates than other cancers (54.1 vs 29.2 %; P = 0.011). Nestin expression rate in ER- and PR-negative tumors was found to be significantly higher than cases that were ER- and PR-positive (P = 0.011 and P = 0.036, respectively). However, it was not found that HER2 expression was related to nestin expression (P = 0.120). These results suggest that the expression of nestin might play an important role in the prognosis of breast carcinoma, especially in the triple-negative subgroups.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to explore the expression of BAF250a protein in breast cancer and its association with the clinical and pathological characteristics and prognosis of breast cancer. The expression status of BAF250a protein was detected by Western blot analysis and immunohistochemical staining. The relationship between BAF250a proteins and clinicopathological parameters in 496 breast cancer specimens was analyzed. Western blot analysis showed that BAF250a protein had a lower expression in breast cancer specimens than in matched normal breast tissue (104.38 ± 11.65 vs. 55.94 ± 10.27; P = 0.004, t test). Among the 496 enrolled breast cancer patients, BAF250a protein expression was absent in 324 (65.3 %). Universal and multiple analyses indicated that BAF250a protein expression loss was significantly related to histological grade, metastatic nodes, tumor node metastasis (TNM) stage, and the expression of estrogen receptor (ER), progesterone receptor (PR), c-erbB-2, and p53 (all P < 0.05). For TNM stage, rank correlation coefficients were 0.199 and 0.191, respectively, (P < 0.05), but BAF250a protein deletion had either a positive or a negative correlation with ER, PR, c-erbB-2, and p53 protein expression (correlation coefficients were 0.231, 0.207, -0.098, -0.128; P < 0.05). Analysis of survival rates showed that the patients with BAF250a protein expression attained a significantly better postoperative disease-specific survival than those with BAF250a protein deletion (88.4 vs. 79.0 %; P = 0.003). In the Cox regression test, BAF250a protein deletion was detected as an independent prognostic factor (P = 0.014). BAF250a protein might be a new potential target for breast cancer treatment.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to investigate the expression and significance of the GRHL3 protein in breast cancer diagnosis and prognosis. Overall, 111 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. The GRHL3 protein expression status in the breast cancers was evaluated by immunohistochemistry. The relationship between GRHL3 protein expression status and clinicopathological factors and the breast cancer prognoses was also determined. In total, 71 (63.96 %) out of 111 cases were found to express GRHL3 protein. GRHL3 expression was higher in breast cancers, compared to other pathologic cancer types (χ (2) = 5.68, P < 0.05). Moreover, GRHL3 protein was also observed to correlate with breast cancer clinical stage and histological grade (χ (2) = 7.99, P < 0.05 and χ (2) = 7.907, P < 0.05, respectively). Interestingly, triple-negative breast cancers had lower expression rates than other breast cancers (41.18 vs. 71.28 %, P < 0.05). GRHL3 was shown to be an independent prognostic factor of breast cancer in Cox regression analysis. Altogether, our results indicate predominant GRHL3 expression in breast cancers, especially non-triple-negative cancers and early stage cancers. GRHL3 expression appeared to decrease with tumor progression. Survival analysis demonstrated the inhibitory effect of GRHL3 in breast cancer. These results strongly suggest the possible involvement of GRHL3 in tumor suppression.
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression status of PIWIL2 and piR-932 in breast cancer stem cells and the role they could play in tumor cell growth and metastasis through Latexin.
CD44(+)/CD24(-) tumor cells (CSC) from clinical specimens were sorted using flow cytometry. PIWIL2 expression status was detected in CSC cells by microarray analysis and 1086 breast cancer specimens by Western blot and immunohistochemistry staining. piR-932 expression was also detected in CSC cells by piRNA microarray assay. The relationship between the PIWIL2 protein and clinico-pathological parameters and prognosis was subsequently determined.
CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. PIWIL2 protein was expressed higher in CSC cells compared to the control cells. In total, 334 (30.76%) of the 1086 breast cases showed high PIWIL2 expression. PIWIL2 was observed to be related to age, tumor size, histological type, tumor stage, and lymph node metastasis (all P < 0.05). Furthermore, we have found that one of the Piwi-interacting RNAs (piRNAs) called piR-932 expressed significantly higher in the breast cancer cells that were induced to EMT, and it could form immune complexes through immunoprecipitation with PIWIL2; in PIWIL2+ breast cancer stem cells, Latexin expression significantly reduced because of its promoter region CpG island methylation.
These results suggest that the combination of piR-932 and PIWIL2 may be a positive regulator in the process of breast cancer stem cells through promoting the methylation of Latexin, and they both could be the potential targets for blocking the metastasis of breast cancer.