Expression In Breast Cancer Patients Research Articles

URG4 expression in invasive breast carcinoma and its relation to clinicopathological characteristics.

Upregulated gene 4 (URG4) is a recently described oncogene that upregulates cell proliferation. Its overexpression has been identified in many malignancies, and it is thought to be related to tumour progression, angiogenesis, metastasis and the recurrence of many cancers. This is the first study to show its expression in breast cancer patients and its association with clinicopathological characteristics in these patients. Fifty invasive ductal breast carcinoma cases and 25 control cases were included in the study. Tumourous tissues and control tissues were assessed molecularly for quantification of mRNA expression of URG4 and immunohistochemically for protein expression of URG4. The mean ages of the patients and controls were 54.3 ± 11.3 and 38.9 ± 9.7 years, respectively. The expression levels of URG4 mRNA in tumour tissues were higher compared to control breast tissues (p = 0.023). An immunohistochemical assessment suggested that URG4 is strongly expressed in normal breast tissues and lower-grade (grades I and II) ductal carcinomas of the breast, but it is weakly expressed in high-grade (grade III) ductal breast carcinomas. Additionally, the immunohistochemical and molecular expression results of URG4 were relevant to most prognostic parameters (tumour size, oestrogen and progesterone receptor status, HER2 status and Ki67 proliferative index) for breast cancer. However, unlike the immunohistochemical studies, the molecular studies revealed that there was no significant difference in URG4 expression for different grades of tumour tissues. The literature data suggest that URG4 overexpression is associated with poor prognosis in many types of cancer. Conversely, our results in breast cancer specimens indicate that URG4 overexpression in breast ductal carcinomas is significantly associated with good prognostic parameters. Nevertheless, these preliminary findings should be confirmed by further studies.

Correlation between Obesity and Contraceptive Method on Estrogen and Progesterone Receptors and Human Epidermal Growth Factor Receptor–2 Expression among Breast Cancer Patients in Dr. Moewardi Hospital, Surakarta

Background: Breast cancer is the number 2 cancer in Indonesia after cervical cancer. Breast cancer increases every year. The formation of breast cancer is stimulated by various factors such as obesity and a history of family planning. In breast cancer, there are three important receptors, namely estrogen (ER) receptors, progesterone receptors (PR), and HER-2/Neu. The purpose of this study was to determine the association of obesity and history of family planning with the estrogen hormone receptor (ER), progesterone hormone receptor (PR), and HER-2/Neu expression in breast cancer patients in the dr. Moewardi Hospital in Surakarta, Central Java. Subjects and Method: This was an analytic observational study carried out at Dr. Moewardi Hospital, Surakarta, Central Java. A sample of 117 pre- and post-menopausal women who performed examinations at the oncology surgical clinic at Dr. Moewardi hospital, Surakarta was selected by total sampling. The dependent variables were estrogen and progesterone receptors and HER-2/Neu expressions. The independent variables were obesity and history of contraceptive method. Data were obtained from the medical record and analyzed by multiple logistic regression. Results: Obesity (OR= 0.29; 95% CI= 0.13 to 0.68; p= 0.004) reduced estrogen hormone receptors and it was statistically significant. History of contraceptive method (OR= 1.18; 95% CI= 0.55 to 2.52; p= 0.680) increased estrogen hormone receptors but it was not statistically signi­ficant. Obesity (OR=0.41; 95% CI= 0.18 to 0.96; p= 0.040) and history of contraceptive method (OR= 0.41; 95% CI= 0.19 to 0.88; p= 0.022) reduced progesterone hormone receptors. Obesity and history of contraceptive method increased Her-2/Neu expression. Conclusion: Obesity reduces estrogen hormone receptors. History of the contraceptive method increases estrogen hormone receptors. Obesity and history of contraceptive method reduce pro­gesterone hormone receptors. Obesity and history of contraceptive method increase Her-2/Neu expression. Keywords: Obesity, contraceptive method, estrogen, progesterone hormones, Her-2/neu Correspondence: Silvia Ari Agustina. Study Program in Midwifery, School of Health Sciences Achmad Yani, Yogya­karta. Jl. Ringroad Barat Ambarketawang, Gamping, Sleman, Yogyakarta. Phone: (0274) 4342000. Email: silvia_ari99@yahoo.com. Indonesian Journal of Medicine (2019), 4(3): 259-265 https://doi.org/10.26911/theijmed.2019.04.03.09

Potential Diagnostic Value of Plasma Long-Chain Non-Coding RNA HIT in Breast Cancer

The current study aims to investigate the expression of HOXA transcript induced by transforming growth factor-β (TGF-β) (HIT) in plasma of women with breast cancer and its potential diagnostic value for breast cancer. qRT-PCR was used to detect the expression of HIT in breast cancer tissues and the plasma of patients with breast cancer. The correlation between the expression of HIT in plasma and clinicopathological parameters of breast cancer was analyzed. The levels of CAl53 and CEA in plasma were also detected. Operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of plasma HIT for breast cancer. Compared with the adjacent tissues, the expression of HIT in breast cancer tissues was significantly increased. Meanwhile, the level of plasma HIT in the breast cancer group was significantly higher than that in the benign lesion group and healthy control group. The level of plasma HIT expression in breast cancer patients was correlated with estrogen receptor (ER) erbB-2 and lymph node metastasis (p < 0.05); the area under ROC curve (AUC) of plasma HIT in diagnosis of breast cancer alone was 0.827 with the sensitivity and specificity of 57.7% and 86.4%. The diagnostic efficacy of HIT, was significantly higher than that of CAl53 and CEA, and the combined diagnostic value of HIT, CAl53 and CEA was also higher than that of any single detection. High expression of HIT in plasma may be a potential biomarker for the diagnosis of breast cancer.

Correlation Between HER-2 Gene Amplification or Protein Expression and Clinical Pathological Features of Breast Cancer.

The incidence of breast cancer in females is gradually increasing. Expression of HER-2 gene and protein is critical for predicting the prognosis of breast cancer. This study examined amplification of HER-2 gene and protein expression in breast cancer patients to analyze their correlation with clinical and pathological features. Specimens of breast gland tissues were collected from breast cancer patients for measuring HER-2 protein expression by immunohistochemistry (IHC) method. Fluorescent in situ hybridization (FISH) measured HER-2 gene amplification. The consistency of HER-2 protein and gene expression was analyzed in addition to their correlation with clinical and pathological features of patients. Thirty-six percent patients showed negative expression of HER-2 protein, and 9%, 32%, and 23% of them had positive expression to different levels (+, ++, and +++). Forty percent patients were positive for HER-2 gene amplification, including 3, 21, and 14 cases of (+), (++), and (+++) patients. Expression of HER-2 protein was highly correlated with HER-2 gene amplification (r = 1.262; p < 0.05). Both parameters were correlated with tumor size, differentiation grade, lymph node metastasis, and TNM stage (p < 0.05). Combined assay of IHC and FISH for detecting HER-2 protein or gene amplification in breast cancer tissues showed their correlation with tumor size, differentiation grade, lymph node metastasis, and TNM stage.

Connexin 43 is an independent predictor of patient outcome in breast cancer patients

PurposeGap junctions are specialized membrane structures that form channels between adjacent cells allowing cell communication. Gap junctions and specifically Connexin 43 (Cx43) are down-regulated in cancer; however, there are contrasting reports on how this effects breast cancer patient survival. This paper is the first large-scale tissue microarray analysis of Cx43 expression in breast cancer patients with an associated clinical long-term follow-up.MethodsUsing a validated TMA of 1118 primary breast cancers, coupled to a comprehensive database of clinicopathological variables, the expression levels and subcellular localisation of Cx43 was assessed by immunohistochemistry. Its impact in terms of survival, distant metastasis-free survival, and clinicopathological variables was determined.ResultsPatients whose tumors expressed high levels of Cx43 had significantly better survival (p < 0.001) than patients with low levels. High Cx43 expression within tumors was associated with an 18-month survival advantage. Loss of Cx43 expression was associated with markers of poor prognosis, namely large tumor size, high grade, high proliferation status, high pleomorphism, high mitosis, poor Nottingham Prognostic Index (NPI), and triple negative tumors. Cx43 expression was independent of tumor size, grade, stage and ER-status in predicting poor survival on multivariate analysis (p = 0.004).ConclusionConnexin 43 (Cx43) is an independent predictor of breast cancer survival and distant metastasis-free survival. High expression of Cx43 was seen in only 13% of tumors, suggesting that drugs to increase Cx43 expression may result in prolonged patients survival.

Clinical Significance of Elevated S100A8 Expression in Breast Cancer Patients.

Breast cancer is the leading cause of female cancer-related death; however, novel biomarkers for predicting cancer recurrence still need to be explored. Aberrant expression of S100A8 has been reported to be related to tumor progression in various cancer types. This study aims to evaluate the clinical significance of S100A8 expression in breast cancer patients. In this study, data from 140 breast cancer patients were retrospectively collected to examine the association between S100A8 expression and clinical prognosis. Increased S100A8 expression was detected in breast cancer patients with relapse. The patients with increased S100A8 levels had significantly shorter disease-free survival (DFS) and overall survival (OS). In a multivariate survival analysis, a high histological grade and an elevated S100A8 level were independent factors associated with poor DFS and OS. Moreover, S100A8 expression was correlated with clinical subtype in breast cancer patients. The results showed that ER-negative and triple-negative breast cancer (TNBC) patients had significantly higher expression of S100A8 than patients with other subtypes. In conclusion, this study identified S100A8 as a potential biomarker for relapse in breast cancer patients.

NKAP functions as an oncogene and its expression is induced by CoCl2 treatment in breast cancer via AKT/mTOR signaling pathway.

PurposeNKAP plays an important role in transcriptional repression, T-cell development, maturation and function acquisition, maintenance and survival of hematopoietic stem cells, and RNA splicing. In this study, we tried to explore the physiological role of NKAP in breast cancer.MethodsWe investigated NKAP expression in breast cancer patients and normal controls and its correlation with survival in breast cancer patients by searching on GEPIA. We knocked down the expression of NKAP in MCF-7 cells by RNAi technique and studied its effect on cell proliferation, migration, invasion, and apoptosis. And we revealed the effect of NKAP on MCF-7 cells under hypoxic conditions in vitro.ResultsNKAP was differentially expressed in breast cancer and normal tissues and is a potential prognostic indicator of breast cancer. Subsequently, NKAP knockdown significantly inhibited the proliferation and clonality of MCF-7 cells and induced its apoptosis through caspase 3-dependent pathway. In addition, knockdown of NKAP could strongly inhibit the migration and invasion of MCF-7 cells. In MCF-7 cells, NKAP affected the AKT/mTOR signaling pathway and markedly reduced the phosphorylation of AKT and mTOR, as well as the downstream protein. What’s interesting is CoCl2 was found to induce NKAP expression in MCF-7 cells. Downregulation of NKAP hindered the impact of CoCl2 on the MCF-7 cells, including cell proliferation and invasion, by adjusting AKT/mTOR signaling.ConclusionNKAP functioned as an oncogene, and its expression was induced by hypoxia in breast cancer via AKT/mTOR signaling pathway.

Does the Sphingosine 1-Phosphate Receptor-1 Provide a Better or Worse Prognostic Outcome for Breast Cancer Patients?

Recently, Lei et al., (2018) published an article in Cancer Medicine claiming a survival benefit of sphingosine 1-phosphate (S1P) and sphingosine 1-phosphate receptor 1 (S1P1) expression in breast cancer patients. This controversial study opposes the prevailing view concerning the deleterious role of S1P in cancer. This is discussed in depth in the current opinion article.

Coronin 1c and F-actin Promote Metastasis of Breast Cancer.

BackgroundWe studies the expression of Coronin 1c and F-actin protein in breast cancer and explored their relationship with breast cancer metastasis.Material/MethodsA total of 210 breast cancer tissues and adjacent normal tissues were collected from January 2013 to December 2014. The expressions of Coronin 1c and F-actin were detected by immunohistochemistry and Western blotting. We analyzed the relationship between Coronin 1c and F-actin and clinical data of breast cancer.ResultsThe expressions of Coronin 1c and F-actin in breast cancer tissues were positively correlated (r=0.926, P<0.05) and were significantly higher than those in normal tissues (P<0.05). The Coronin 1c and F-actin expressions were not correlated with age, tumor size, ER expression, or PR expression in breast cancer patients (P>0.05), but were significantly correlated with HER-2 expression, histological grade, lymph node metastasis, molecular classification, and TNM (P<0.05). The expression of HER-2 in breast cancer tissues was positively correlated with the expression of Coronin 1c (r=0.706, P<0.05) and F-actin 1c, while F-actin protein in breast cancer tissues with lymph node metastasis was significantly higher than in those without lymph node metastasis (P<0.05).ConclusionsCoronin 1c protein and F-actin protein are highly expressed in breast cancer and their expression may be related to the metastasis of breast cancer cells.

Abstract 5497: Effective combination therapy for breast cancer targeting BACH1 and mitochondrial metabolism

Abstract Oxidative phosphorylation is an attractive target for cancer therapy. Reprogramming metabolic pathways by promoting oxidative phosphorylation could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options like triple negative breast cancer (TNBC). Here we show that BACH1, a heme-binding transcription factor whose expression is enriched in patients with TNBC, inhibits oxidative phosphorylation through direct transcriptional regulation of electron transport chain (ETC) gene expression. Treatment of cells with hemin, which induces BACH1 degradation, mimics BACH1 depletion with shRNA. Pretreatment of TNBC tumors with BACH1 shRNA or hemin overcame resistance to metformin, an anti-diabetic drug, and abolished the growth of both cell line and patient-derived tumor xenografts. BACH1 gene expression inversely correlated with ETC gene expression in breast cancer patients as well as other tumor types, highlighting the clinical relevance. This study demonstrates that oxidative phosphorylation represents an Achilles heel that can be exploited through targeting BACH1 to sensitize breast cancer and potentially other tumor tissues to mitochondrial inhibitors. Citation Format: Jiyoung Lee, Ali Yesilkanal, Casey Frankenberger, Mohamad Elbaz, Daniel Rabe, Jielin Yan, Felicia Rustandy, Peter Hart, Christie Kang, Elizabeth Grossman, Jason Locasale, Daniel Nomura, Marcelo Bonini, Marsha Rosner. Effective combination therapy for breast cancer targeting BACH1 and mitochondrial metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5497.

Abstract B75: Nutritional profiling reveals glutamine-utilizing transaminases as a metabolic vulnerability of TAZ/YAP-driven breast cancer cells

Abstract The aberrant activity of the transcriptional regulators TAZ and YAP (TAZ/YAP) drives many oncogenic traits, including the resistance to cell death, sustaining cell growth, and control of cell fate. Aggressive breast cancers in particular exhibit high TAZ/YAP levels and activity, and thus understanding the roles of these factors may offer therapeutic opportunity for these poorly treatable diseases. Here, we report that TAZ/YAP play an important role in driving breast cancer dependency to exogenous glutamine, an abundant amino acid that has emerged as central for tumor growth. We observed that breast cancer cells with high levels of TAZ/YAP are more sensitive to glutamine deprivation, and that knockout of TAZ/YAP in these cells alleviated defects resulting from glutamine. Rescue experiments with glutamine-derived metabolites suggested an essential role for glutamate and α-ketoglutarate (AKG) in TAZ/YAP-driven cell growth. Analysis of enzymes mediating the conversion of glutamate to α-ketoglutarate (AKG) showed that TAZ/YAP induce the expression of distinct transaminases, and that TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients. Notably, the transaminase inhibitor aminooxyacetate (AOA) repressed cell growth in a TAZ/YAP-dependent manner, identifying transamination as a potential vulnerable metabolic requirement for TAZ/YAP-driven breast cancer. Considering the link between breast cancer risk and obesity, and the connection between obesity-driven metabolic changes to glutamine metabolism, our study offers a potential direction for future therapeutic targeting of aggressive breast cancers in underserved populations, where obesity is becoming a prevalent factor. Citation Format: Eleni Stampouloglou, Nathan Kingston, Chih-Sheng Yang, Liye Zhang, Stefano Monti, Xaralabos Varelas. Nutritional profiling reveals glutamine-utilizing transaminases as a metabolic vulnerability of TAZ/YAP-driven breast cancer cells [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B75.

Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells.

The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro-tumorigenic factors that drive many oncogenic traits, including induction of cell growth, resistance to cell death, and activation of processes that promote migration and invasion. Here, we report that TAZ/YAP reprogram cellular energetics to promote the dependence of breast cancer cell growth on exogenous glutamine. Rescue experiments with glutamine-derived metabolites suggest an essential role for glutamate and α-ketoglutarate (AKG) in TAZ/YAP-driven cell growth in the absence of glutamine. Analysis of enzymes that mediate the conversion of glutamate to AKG shows that TAZ/YAP induce glutamic-oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression and that TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients. Notably, we find that the transaminase inhibitor aminooxyacetate (AOA) represses cell growth in a TAZ/YAP-dependent manner, identifying transamination as a potential vulnerable metabolic requirement for TAZ/YAP-driven breast cancer.

465 (PB-098) - Caspase14 expression is associated with triple negative phenotypes and cancer stem cell marker expression in breast cancer patients

465 (PB-098) - Caspase14 expression is associated with triple negative phenotypes and cancer stem cell marker expression in breast cancer patients

The creative psychosocial genomic healing experience (CPGHE) and gene expression in breast cancer patients: A feasibility study

BackgroundBiomarkers associated with inflammation and immune function are increasingly being used to examine mechanisms of the effects of mind-body therapies. Less researched are biomarkers associated with cognitive and executive functioning in the study of mind-body therapy mechanisms and effects. This study explored the feasibility of recruiting breast cancer patients (BCPs) and implementation fidelity of participation in a research project utilizing the 4-stage Creative Psychosocial Genomic Healing Experience (CPGHE), a mind-body protocol that is theorized to create epigenetic effects via targeted psychological change in emotional triggers in coping with cancer. MethodsEight BCPs were identified as eligible (stages I, II, III, early phases of treatment) and five consented to one of two intervention groups (allocated to a single session or two sessions of CPGHE). Blood draws were examined pre- and post-intervention for a stress/inflammation gene expression marker, Nuclear Factor kappa-B (NF-kB), and three markers associated with synaptic plasticity undergirding cognitive and executive functioning: Early Growth Response 1 (EGR1), activity-regulated cytoskeleton-associated protein (Arc), and brain-derived neurotrophic factor (BDNF). ResultsOne consented BCP dropped out due to illness. The remaining four adhered to the 4-stage CPGHE protocol and found the CPGHE experience beneficial. Blood samples for the gene expression results were collected and processed according to planned protocol without incident. ConclusionImplementing the CPGHE and achieving good adherence among a sample of BCPs is feasible. Processing of blood samples collected from BCPs for gene expression data is also feasible.

HOXD3 Plays a Critical Role in Breast Cancer Stemness and Drug Resistance

Background/Aims: Homeobox D3 (HOXD3) is a member of the homeobox family of genes that is known primarily for its transcriptional regulation of morphogenesis in all multicellular organisms. In this study, we sought to explore the role that HOXD3 plays in the stem-like capacity, or stemness, and drug resistance of breast cancer cells. Methods: Expression of HOXD3 in clinical breast samples were examined by RT-PCR and immunohistochemistry. HOXD3 expression in breast cancer cell lines were analyzed by RT-PCR and western blot. Ability of drug resistance in breast cancer cells were elevated by MTT cell viability and colony formation assays. We examined stemness using cell fluorescent staining, RT-PCR and western blot for stem cell marker expression. Finally, activity of wnt signaling was analyzed by FOPflash luciferase assays. RT-PCR and western blot were performed for downstream genes of wnt signaling. Results: We demonstrated that HOXD3 is overexpressed in breast cancer tissue as compared to normal breast tissue. HOXD3 overexpression enhances breast cancer cell drug resistance. Furthermore, HOXD3 upregulation in the same cell lines increased sphere formation as well as the expression levels of stem cell biomarkers, suggesting that HOXD3 does indeed increase breast cancer cell stemness. Because we had previously shown that HOXD3 expression is closely associated with integrin β3 expression in breast cancer patients, we hypothesized that HOXD3 may regulate breast cancer cell stemness and drug resistance through integrin β 3. Cell viability assays showed that integrin β 3 knockdown increased cell viability and that HOXD3 could not restore cancer cell stemness or drug resistance. Given integrin β 3’s relationship with Wnt/β-catenin signaling, we determine whether HOXD3 regulates integrin β 3 activity through Wnt/β-catenin signaling. We found that, even though HOXD3 increased the expression of Wnt/β-catenin downstream genes, it did not restore Wnt/β-catenin signaling activity, which was inhibited in integrin β3 knockdown breast cancer cells. Conclusion: We demonstrate that HOXD3 plays a critical role in breast cancer stemness and drug resistance via integrin β3-mediated Wnt/β-catenin signaling. Our findings open the possibility for improving the current standard of care for breast cancer patients by designing targeted molecular therapies that overcome the barriers of cancer cell stemness and drug resistance.

Long noncoding RNA SNHG15 promotes human breast cancer proliferation, migration and invasion by sponging miR-211-3p

Long non-coding RNAs (lncRNA) have been demonstrated to act as essential regulators in the development and progression of breast cancer. In our study, we found that long noncoding RNA SNHG15 was highly expressed in breast cancer tissues and cell lines. And the expression of SNHG15 was correlated with TNM stage, lymphnode metastasis and survival in breast cancer patients. SNHG15 knockdown significantly inhibited the proliferation and induced apoptosis in breast cancer cells in vitro and in vivo. Besides, SNHG15 downregulation suppressed cell migration and invasion in MCF-7 and BT-20 cells, and inhibited epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG15 acted as a competing endogenous RNA to sponge miR-211-3p, which was downregulated in breast cancers and inhibited cell proliferation and migration. Our results showed that there was a negative correlation between SNHG15 and miR-211-3p expression in breast cancer patients. Collectively, we, for the first time, revealed the functions of SNHG15 and miR-211-3p in breast cancer.

31P - Tumor-infiltrating lymphocytes, tumor-associated macrophages and HLA class 1 expression in breast cancer patients treated with neoadjuvant chemotherapy with or without zoledronic acid: A sub study of the NEOZOTAC trial

31P - Tumor-infiltrating lymphocytes, tumor-associated macrophages and HLA class 1 expression in breast cancer patients treated with neoadjuvant chemotherapy with or without zoledronic acid: A sub study of the NEOZOTAC trial

36P - Prognostic significance of circulating microRNA-155 expression in breast cancer patients

36P - Prognostic significance of circulating microRNA-155 expression in breast cancer patients

Long non-coding RNA00544 serves as a potential novel predictive and prognostic marker for HR+\u2009HER2\u2212 subtype breast cancer

Luminal breast cancers (BC) account for majority of breast cancer. Due to its heterogeneity and the development of treatment resistance, luminal BC patients can vary substantially. Long noncoding RNAs (lncRNAs), as we known, is involved in breast cancer progression. Here, we aim to identify the lncRNAs which are involved in the particular type luminal BC progression. By Gene Chips analysis, we found a novel lncRNA00544, which was highly expressed in the metastatic axillary nodes compared with corresponding luminal BC tissues (fold change = 2.26, P = 0.043). This result was confirmed in luminal BC cell lines (p = 0.0113) and 49 paired breast cancer samples compared with in corresponding controls (p = 0.011). Furthermore, Kaplan–Meier survival curves of 373 breast cancer patients indicated that disease-free survival was significantly poor in breast cancer patients with high lncRNA00544 expression (p < 0.001). Univariate and multivariate Cox regression analyses showed that lncRNA00544 was a significant independent prognostic biomarker in luminal BC patients. Further analysis showed that the prognosis of high lncRNA00544 expression in breast cancer patients was actually related to HR + HER2− subtype. Together, our studies indicate that lncRNA00544 may represent a novel predictive and prognostic indicator in luminal BC patients.

Elevated FKBP52 expression indicates a poor outcome in patients with breast cancer.

The 52-kDa FK506-binding protein (FKBP52), a regulator of steroid hormone receptor signaling, is potentially involved in a variety of hormone-dependent cancer types. The present study investigated the expression and clinical implications of FKBP52 in breast cancer. Immunohistochemistry was performed on samples from 145 breast cancer patients and on 66 unmatched breast non-cancerous tissues (as controls) to determine the expression level of FKBP52. Publicly available microarray and RNA-seq datasets used in the present study were downloaded from the European Bioinformatics Institute ArrayExpress. Kaplan-Meier survival analysis was also performed. FKBP52 expression was moderately higher in the tumors than that in the non-cancerous tissues, but this difference was not statistically significant (P=0.176). However, available microarray datasets exhibited a significant difference in FKBP52 mRNA levels between breast tumors and controls. In the 145 breast cancer patients, elevated FKBP52 expression was significantly associated with advanced Tumor-Node-Metastasis (TNM) stage (P=0.015), lymph node metastasis (P=0.015) and tumors with poor histological differentiation (P=0.047). FKBP52 expression was negatively associated with estrogen receptor expression (P=0.033), but positively associated with human epidermal growth factor receptor 2 expression (P=0.033). However, there was no association between FKBP52 and progesterone receptor expression. Survival analyses demonstrated that FKBP52 was indicative of a poor overall survival rate (P=0.026), which was consistent with the result of Kaplan-Meier analysis, exhibiting a negative association between the mRNA of FKBP52 and overall survival (OS) (P=0.044). Other than for FKBP52 [hazard ratio (HR), 2.315; 95% confidence interval (CI), 1.077–4.975; P=0.032], univariate analysis revealed that clinical stage exhibited a significant influence on the prognosis of the breast cancer patients (HR, 2.148; 95% CI, 1.011–4.566; P=0.047). However, multivariate analysis revealed that only clinical stage, not FKBP52, was an independent prognostic factor (HR, 2.721; 95% CI, 1.169–6.335; P=0.020). Patients were further classified according to their OS. Compared with the controls (3.94±2.992), FKBP52 expression in breast cancer patients with OS of ≤3 years (5.39±3.409; P=0.042) or OS of ≤5 years (5.88±3.473; P=0.005) was significantly increased, respectively. However, no significant difference in FKBP52 expression was observed between controls and individuals with an OS time of >3 years (4.84±3.769; P=0.109) or >5 years (5.32±3.372; P=0.090). Elevated FKBP52 expression may be involved in tumor progression and invasion, given its positive association with TNM stage and lymph node metastasis. Although it is not an independent predictor, FKBP52 has promise as a biological marker for estimating the progression of breast cancer.