Downregulated expression of ARHGAP10 correlates with advanced stage and high Ki-67 index in breast cancer

Background Rho GTPase-activating protein 10 (ARHGAP10), which catalyzes the conversion of active Rho GTPase to the inactive form, is downregulated in some cancers. However, little is known about ARHGAP10 in breast cancer. Methods The transcriptional expression level of ARHGAP10 in breast cancer was analyzed with the data downloaded from The Cancer Genome Atlas (TCGA) and Oncomine, then verified by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) in 30 pairs of breast cancer tissues and the corresponding adjacent normal tissues. ARHGAP10 protein expression was examined by immunohistochemistry (IHC) in 190 breast cancer and 30 corresponding adjacent normal breast tissue samples. The associations between ARHGAP10 expression and clinicopathological characteristics of patients were analyzed, and Kaplan–Meier Plotter was used to assess the relationship between ARHGAP10 and relapse-free survival (RFS). Different expression levels of ARHGAP10 in response to chemotherapy agents were determined by GEO2R online tool. The potential biological functions of ARHGAP10 were analyzed by Gene Set Enrichment Analysis (GSEA) using data downloaded from TCGA. Results ARHGAP10 mRNA and protein expression was lower in breast cancer tissues than in adjacent normal tissues. Low expression of ARHGAP10 was associated with advanced clinical TNM (cTNM) stage (pb = 0.001) and high Ki-67 index (p = 0.015). Low expression of ARHGAP10 indicated worse RFS (p = 0.0015) and a poor response to chemotherapy (p = 0.006). GSEA results showed that ARHGAP10 was involved in signaling pathways including protein export, nucleotide excision repair, base excision repair, focal adhesion, JAK-STAT pathway and the actin cytoskeleton.

Download Full-text

Meta-analysis of the clinicopathological significance of miRNA-145 in breast cancer

Bioscience Reports ◽

10.1042/bsr20193974 ◽

2020 ◽

Vol 40 (9) ◽

Author(s):

Peng Lv ◽

Zhenzhu Zhang ◽

Li Hou ◽

Yayue Zhang ◽

Lingeng Lu ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cancer Patients ◽

Human Cancer ◽

Meta Analysis ◽

Normal Breast ◽

Breast Cancer Patients ◽

Normal Tissues ◽

Cancer Tissues ◽

Low Expression

Abstract Low expression of tumor suppressor microRNA (miRNA) and high expression of carcinogenic miRNA promote the occurrence and progression of human cancer. Most studies show that miR-145 is a tumor suppressor miRNA, and is closely related to the clinicopathology of breast cancer. However, the results are still inconsistent. Therefore, we conducted a meta-analysis on the basis of eligible studies to summarize the possible correlation between miR-145 and the clinicopathology and prognosis of breast cancer. Using PubMed, Embase, Web of Science, Wanfang and CNKI, we searched all published papers written in either English or Chinese on miR-145 expression in breast cancer from 1990 to November 2019 for meta-analysis. We used standardized mean difference (SMD) to evaluate the differential expression of miR-145 in breast cancer tissues and adjacent normal tissues or normal breast tissues. We found that miR-145 expression was significantly lower in breast cancer tissues than that in adjacent normal tissues (SMD = −2.93, P<0.0001) and in healthy women (SMD = −0.52, P=0.009). miR-145 expression was lower in breast cancer patients with ER-positive (SMD = 0.65, P<0.001), HER-2-positive (SMD = −1.04, P<0.001), compared with their counterparts, respectively. In addition, breast cancer patients with low expression of miR-145 had larger tumor diameters (SMD = −1.97, P<0.001) and lymph node metastasis (SMD = −1.75, P<0.001) that are unfavorable prognostic factors. Conclusion: Low miR-145 is observed in breast cancer, which is closely related to molecular subtypes and unfavorable factors of breast cancer. These findings indicate that miR-145 is tumor suppressor miRNA, and may be a potential diagnostic and prognostic marker in breast cancer.

Download Full-text

Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

Scientific Reports ◽

10.1038/s41598-020-79248-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anna E. M. Bastiaansen ◽

A. Mieke Timmermans ◽

Marcel Smid ◽

Carolien H. M. van Deurzen ◽

Esther S. P. Hulsenboom ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Glutamate Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Metabotropic Glutamate Receptor ◽

Metabotropic Glutamate ◽

Metabotropic Glutamate Receptor 1 ◽

Novel Target ◽

Cancer Tissues

AbstractNew therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03–24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06–20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16–223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

Download Full-text

Comprehensive Analysis of ESRRA in Endometrial Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821992083 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199208

Author(s):

Shufang Wang ◽

Xinlong Huo

Keyword(s):

Endometrial Cancer ◽

Protein Expression ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Operating Characteristics ◽

Protein Expression Level ◽

Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

Download Full-text

Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djs438 ◽

2012 ◽

Vol 104 (23) ◽

pp. 1815-1824 ◽

Cited By ~ 82

Author(s):

V. M. Neumeister ◽

V. Anagnostou ◽

S. Siddiqui ◽

A. M. England ◽

E. R. Zarrella ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Quantitative Assessment ◽

Ischemic Time ◽

Cold Ischemic Time ◽

Cancer Tissues

Download Full-text

Identification of death-associated protein-like 1 (DAPL1) as a novel prognostic biomarker of breast cancer

10.21203/rs.2.24569/v1 ◽

2020 ◽

Author(s):

Haichao Zhang ◽

Xin Qu ◽

Lu Han

Keyword(s):

Breast Cancer ◽

Dna Repair ◽

Survival Data ◽

Immune Cell ◽

Excision Repair ◽

Analysis Data ◽

Clinical Prognosis ◽

Free Survival ◽

Normal Tissues ◽

M1 Macrophage

Abstract Background: It is meaningful to identify the potential clinical prognosis-associated oncogenes for cases with breast cancer, considering the complicated pathogenesis of breast cancer.Methods: We first utilized the bioinformatics approach to investigate the role of the DAPL1 (death-associated protein-like 1) in breast cancer, based on the available datasets of TCGA and GEO.Results: DAPL1 is lowly expressed in breast cancer tissues compared with the normal tissues. For the breast cancer cases of the TCGA-BRCA cohort, we observed a correlation between lowly expressed DAPL1 gene and poor clinical prognosis of overall survival ( P =0.0028). Based on the survival data of GEO, the low DAPL1 expression was associated with a poor prognosis of distant metastasis free survival ( P =0.0023), and relapse free survival ( P =0.0065). DAPL1 expression was linked to the mutation status or copy number variation o f several genes, such as MAP3K1 , NUP98 , and CCDC59. The infiltration level of immune cells (e.g., M1 macrophage, Follicular B helper T cells, etc.) may be involved in the etiology of breast cancer. Based on the DAPL1 -correlated genes, GSEA, GO, and KEGG analysis data indicated the association between DAPL1 expression and a series of biological issues, such as DNA packaging complex, DNA repair complex, nucleotide excision repair, ubiquitin-like protein binding, and ubiquitin proteasome pathway. We also identified several DAPL1 -associated phosphorylation kinases, such as MAPK, PRKACA, and GSK3B.Conclusions: DAPL1 gene is first identified as a prognosis biomarker of breast cancer, and the underlying molecular mechanism involves protein phosphorylation, immune cell infiltration, and DNA repair or protein ubiquitin-associated cellular pathways.

Download Full-text

Investigation of olfactory receptor family 51 subfamily j member 1 (OR51J1) gene susceptibility as a potential breast cancer-associated biomarker

PLoS ONE ◽

10.1371/journal.pone.0246752 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246752

Author(s):

Maryam Asadi ◽

Nahid Ahmadi ◽

Simin Ahmadvand ◽

Ali Akbar Jafari ◽

Akbar Safaei ◽

...

Keyword(s):

Breast Cancer ◽

Statistical Analysis ◽

Protein Expression ◽

Olfactory Receptor ◽

Mrna Level ◽

Expression Level ◽

Pcr Analysis ◽

Normal Tissues ◽

Qrt Pcr ◽

Human Protein Atlas

Among cancer treatment methods, targeted therapy using cancer-associated biomarkers has minimum side effects. Recently olfactory receptor (OR) family attracts the researcher’s attention as a favorable biomarker of cancer. Here, a statistical approach using complete data from the human protein atlas database was used to evaluate the potential of OR51J1 gene as a cancer-associated biomarker. To confirm the findings of statistical analysis, the OR51J1 mRNA and protein expression levels in breast tumor and normal tissue were measured using quantitative Real Time PCR (qRT-PCR) and immunohistochemistry (IHC) techniques. The association with clinicopathological factors was analyzed. Statistical analysis revealed that OR51J1 has a high expression level in more than 20 types of cancer tissues without any expression in 44 normal tissues. In 15 cancer types, including breast cancer, expression score was more than 90%. The qRT-PCR analysis in breast cancer showed OR51J1 have significantly higher expression level in tumors than normal tissues (2.91 fold). The IHC results showed OR51J1 expression on other cellular subtypes than tumor and normal cells, including myoepithelium, fibroblast, and lymphocytes. OR51J1 protein expression in invasive cells, as well as its overall score, showed a significant correlation with ER and PR expression and breast cancer (BC) subtypes. Results revealed the potential of OR51J1 as a cancer-associated biomarker for the diagnosis of breast cancer at the mRNA level.

Download Full-text

The expression and clinical significance of GADD45A in breast cancer patients

PeerJ ◽

10.7717/peerj.5344 ◽

2018 ◽

Vol 6 ◽

pp. e5344 ◽

Cited By ~ 4

Author(s):

Junnan Wang ◽

Yiran Wang ◽

Fei Long ◽

Fengshang Yan ◽

Ning Wang ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Patients ◽

Clinical Significance ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Patients ◽

Ki 67 ◽

Expression Levels ◽

Cancer Tissues

BackgroundGrowth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) was previously found to be associated with risk of several kinds of human tumors. Here, we studied the expression and clinical significance of GADD45A in breast cancer.MethodsWe performed an immunohistochemical study of GADD45A protein from 419 breast cancer tissues and 116 adjacent non-neoplastic tissues.ResultsSignificantly high GADD45A expression were observed in breast cancer tissues compared with adjacent non-neoplastic tissues (P < 0.001) and were independently correlative with estrogen receptor negative (P = 0.028) and high Ki-67 index (P < 0.001). Kaplan–Meier survival analysis revealed that patients with high GADD45A expression levels had a worse long-term prognosis in triple negative breast cancer (P = 0.041), but it was not an independent prognostic factor in multivariate analysis (P = 0.058).ConclusionsGADD45A expression levels are significantly correlative with estrogen receptor status and Ki-67 index in human breast cancer. Patients with triple negative breast cancer might be stratified into high risk and low risk groups based on the GADD45A expression levels.

Download Full-text

The glycobiological landscape of breast cancer: insights into galectins and O-GlcNAc homeostasis-related genes

10.21203/rs.3.rs-898135/v1 ◽

2021 ◽

Author(s):

Rada Tazhitdinova ◽

Alexander V Timoshenko

Keyword(s):

Breast Cancer ◽

Cancer Biology ◽

Breast Cancer Subtype ◽

The Cancer Genome Atlas ◽

Correlation Relationship ◽

Cancer Data ◽

Normal Tissues ◽

Genes Encoding ◽

Genetic Landscape ◽

Cancer Tissues

Abstract Purpose This study aimed to assess the functional associations between genes of the glycobiological landscape encoding galectins and O-GlcNAc cycle enzymes in the context of breast cancer biology and clinical applications. Methods An in silico analysis of the breast cancer data from The Cancer Genome Atlas was conducted comparing expression, pairwise correlations, and prognostic value for 17 genes encoding galectins, O-GlcNAc cycle enzymes, and cell stemness-related transcription factors. Results Multiple general and breast cancer subtype-specific differences in galectin/O-GlcNAc genetic landscape markers were observed and classified. Specifically, LGALS12 was found to be significantly downregulated in breast cancer tissues across all subtypes while LGALS2 and GFPT1 showed potential as prognostic markers. Remarkably, there was an overall loss of both correlation strength and correlation relationship between expression of galectin/O-GlcNAc landscape genes in the breast cancer samples versus normal tissues. Six gene pairs (GFPT1/LGALS1, GFPT1/LGALS3, GFPT1/LGALS12, GFPT1/KLF4, OGT/LGALS12, and OGT/KLF4) were found to be potential diagnostic markers for breast cancer. Conclusions These findings indicate that the glycobiological landscape of breast cancer underwent significant remodeling, which might be associated with switching galectin gene regulation within a framework of O-GlcNAc homeostasis.

Download Full-text

The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

European Journal of Inflammation ◽

10.1177/2058739219828236 ◽

2019 ◽

Vol 17 ◽

pp. 205873921982823

Author(s):

Yuelou Yang ◽

Xiangjun Jiang ◽

Dong Li ◽

Feiyan Wang ◽

Qun Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Western Blot ◽

Clinical Significance ◽

Normal Mucosa ◽

Normal Tissues ◽

Positive Rate ◽

Her 2 ◽

Cancer Tissues ◽

Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

Download Full-text

Expressions of miR-21 and miR-210 in Breast Cancer and Their Predictive Values for Prognosis

Iranian Journal of Public Health ◽

10.18502/ijph.v49i1.3048 ◽

2020 ◽

Author(s):

Xiaofei WU

Keyword(s):

Breast Cancer ◽

Normal Tissue ◽

Breast Cancer Tissue ◽

Clinical Staging ◽

Cancer Tissue ◽

Adjacent Normal Tissue ◽

Normal Tissues ◽

Qrt Pcr ◽

Node Metastasis ◽

Low Expression

Background: We aimed to investigate the expressions of miR-21 and miR-210 in the breast cancer tissue and their correlation with clinicopathological features and prognosis. Methods: A retrospective analysis was performed on 68 patients with breast cancer treated surgically in Wuhan General Hospital of Guangzhou Military in 2014-2015. The breast cancer tissue and the adjacent normal tissue were collected from the patients. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miR-21 and miR-210 in the breast cancer and adjacent normal tissues. Results: According to qRT-PCR, the expression levels of miR-210 and miR-21 in the breast cancer tissue were significantly higher than those in the adjacent normal tissue (P<0.05), which were significantly correlated with lymph node metastasis, clinical staging and differentiation of patients (P<0.05). miR-21 and miR-210 were significantly positive correlated in both breast cancer tissues and adjacent normal tissues (r=0.7014, 0.7502, P<0.001). The survival rate in the miR-210 high expression group was significantly lower than that in the miR210 low expression group (P<0.05), whereas there was no significant difference between the miR-21 high and low expression groups. Conclusion: miR-21 and miR-210 are highly expressed in the breast cancer tissue and significantly correlated with lymph node metastasis, clinical staging and differentiation. miR-210, the up-regulated expression of which is related to the poor prognosis of patients with breast cancer, may be a potential prognostic indicator for breast cancer, which can be used to judge the prognosis.

Download Full-text