Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significa...Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.展开更多
OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investi...OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells.METHODS Immunohistochemistry （S-P） was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues. Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells, and uPA expression after treatment with SB203580, a specific inhibitor of p38 MAPK.RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively. The expression of p-p38 was positively related to the expression of uPA （r = 0.316, P 〈 0.05）. The expression of p-p38 and uPA was related to lymph node metastasis and the TNM stage （P 〈 0.05）, but it was not related to the patient＇s age or tumor size （P 〉 0.05）. The expression of p-p38 and uPA in MDA- MB-231 cells was higher than that in MCF-7 cells. SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression.CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression ,and it may be an important process in breast cancer invasion and metastasis.展开更多
Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressiv...Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.展开更多
Breast cancer is one of the world＇s most urgent health problems. The first symptoms of mammary malignancies are manifested only at an advanced stage with significant mortality. Detecting this disease at an early stag...Breast cancer is one of the world＇s most urgent health problems. The first symptoms of mammary malignancies are manifested only at an advanced stage with significant mortality. Detecting this disease at an early stage gives the majority of patients a better chance of survival. The aim was to search for changes in gene expression of specific tumor vascular markers like death receptor 6 （Dr6） and glycoprotein M6B （Gpm6B） in the blood of patients with breast cancer. All subjects were divided into two groups. First group with patients are with different grades of breats tumors （n = 30）. Second group consists from healthy women （n = 15）. After isolation of mRNA from blood, RT-PCR was followed by gel electrophoresis. For statistical analysis one-way ANOVA was used with Student＇s T test using GraphPad InStat software. Significant changes in mRNA levels of gene Dr6 in all grades of first stage breast cancer were detected. The mRNA levels of Dr6 showed a rising tendency from GI （116% higher value than control） to G3 （198% higher than control）. During monitoring of the mRNA level of Gpm6B, a weaker increase was observed than in Dr6. The difference in GI was only 8% higher compared with controls and 44% at G3. From our results it can be concluded that DR6 is a more suitable marker for the diagnosis of breast malignancies in the early stages than Gpm6B. In our work, a non-invasive method for more timely and precise determination of the earlier stages of breast cancer is described, which could also contribute to monitoring the effectiveness of treatment, or regression of this disease.展开更多
Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study ...Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study the effect on bone mineral density （BMD） and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients, for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol. Methods： One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 rag/day （n = 50） or Anastrozole 10 mg （n = 50）. Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups. Results： Use of Tamoxifen was associated with significant annual decrease in osteocalcin （P = 0.001）, whereas Anastrozole group had gradual increase of the annual levels （P 〈 0.01）. BMD decreased significantly in Anastrozole versus Tamoxifen groups （2.6% vs. 0.4%, P 〈 0.001）. Osteoporosis T 〈 -2.5 was reported significantly higher in Anastrozole group （P 〈 0.01）. Women with initial osteopenia in Anastrozole group showed significant decrease in BMD （P 〈 0.05）. The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD. Conclusion： Tamoxifen preserves BMD in postmenopausal breast cancer patients, whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy, moreover, the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.展开更多
Breast cancer is a complex and heterogeneous disease with different clinical outcomes. The investigations of new biomolecular markers are essential to know the prognosis and improve the clinical management of patients...Breast cancer is a complex and heterogeneous disease with different clinical outcomes. The investigations of new biomolecular markers are essential to know the prognosis and improve the clinical management of patients. The SIRT-1 （sirtuin- 1） is a histone deacetylase implicated in various epigenetic critical functions for the cells and the maintenance of genomic stability. The objective of this study is to investigate the grade of expression of the SIRT-I （sirtuin-1） and the prognostic value in overall survival of women with breast cancer. Retrospective cohort of 457 women with breast cancer has been researched, undergoing treatment in Erechim-RS from 2003 to 2013 and followed until July 2015. The degree of SIRT-1 expression was investigated by immunohistochemistry in 123 patients （26.9%） of the cohort. The OS （overall survival） from specific disease and risk of death from breast cancer were estimated by Kaplan-Meier and Cox＇s proportional risks. The median age of 57.4 years cohort with OS of 79.6% in 5 years and 69.1% at 10 years, with follow-up time of 61.9 months are revealed in this work. The SIRT-1 overexpression was found in 6.5% of cases and characterized a subgroup of women with shorter survival and increased risk of death from breast cancer （HR = 2.66; 95% CI 1.03 to 6.86; p = 0.043） and adjusted by age （HR = 2.86; 95% CI 1.11 to 7.38; p = 0.030）, histology （HR = 2.79; 95% CI 1.07 to 7.28; p = 0.036）, lymph nodes （HR = 2.73; 95% CI 1.06 to 7.04; p = 0.037）, Her-2 （HR = 2.82; 95% CI 1.07 to 7.44; p = 0.036）; chemotherapy （HR = 2.90; 95% CI 1.11 to 7.60; p = 0.030） and radiotherapy （HR = 2.71; 95% CI 1.05 to 7.01; p = 0.040）. In regressive multivariate models adjusted for age, status of axillary lymph nodes, Her-2 expression and proliferation index （Ki-67）, the grade of expression of the SIRT-1 maintained association with poor prognosis. From the study, it can be concluded that the assessment of the SIRT-1 expression is an independent prognostic biomarker in breast cancer.展开更多
Objective To screen the target gene UBE2C and explore its prognostic value and immune correlation in breast cancer(BRCA)using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from...Objective To screen the target gene UBE2C and explore its prognostic value and immune correlation in breast cancer(BRCA)using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO)and analyzed to obtain differentially expressed genes(DEGs).Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs.Then the key gene UBE2C was determined using R language,STRING,and Cytoscape,and the differential expression of UBE2C was verified using the external datasets,The Cancer Genome Atlas(TCGA),and quantitative real-time PCR(qRT-PCR).The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language,TIMER,and Gene Set Enrichment Analysis(GSEA).Results The expression of UBE2C was differentially upregulated in BRCA,as verified by TCGA and qRT-PCR.Prognostic analysis revealed that UBE2C served as an independent prognostic factor.High expression of UBE2C was associated with decreased immune infiltration levels of B cells,CD4+T cells,CD8+T cells,macrophages,and myeloid dendritic cells in BRCA tissue.The expression of UBE2C in BRCA showed a significant correlation with PDCD1,CD274,and CTLA4 expressions.There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability.GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues can predict the survivals and prognosis of BRCA patients.Also,it is closely related to the BRCA immune microenvironment and can predict the effecacy of immunotherapy in BRCA patients.Therefore,UBE2C may be an potential immune-related prognostic biomarker for BRCA.展开更多
Overexpression of thioredoxin reductase has been identified in a variety of primary tumors, suggesting the levels of TrxR activity between tumor patients and normal people are potentially different. Here, we performed...Overexpression of thioredoxin reductase has been identified in a variety of primary tumors, suggesting the levels of TrxR activity between tumor patients and normal people are potentially different. Here, we performed a study to investigate the differences of TrxR activity between normal people and breast tumor patients, with the expectation that TrxR activity can be considered as a novel biomarker involved in breast cancer diagnosis and treatment. In this study, we have demonstrated for the first time that TrxR levels in breast cancer patients before therapy were significantly higher than those of normal people （P〈0.05）. No significant difference of TrxR activity was found among the patients at different stages of breast tumor progression. In the patient group of TrxR 〈10 U/mL, evaluation of TrxR activity has shown a high consistency with the results from cancer diagnostic imaging. Overall, these observations suggest TrxR as an effective biomarker to monitor and evaluate the clinical outcome of breast cancer therapeutics, and identify TrxR activity as a novel approach for breast cancer early-stage detection.展开更多
The tumor-promoting arm of transforming growth factor beta(TGF-β)receptor signaling contributes to advanced cancer progression and is considered a master regulator of breast cancer metastasis.In mammals,there are six...The tumor-promoting arm of transforming growth factor beta(TGF-β)receptor signaling contributes to advanced cancer progression and is considered a master regulator of breast cancer metastasis.In mammals,there are six distinct members in the tumor-necrosis factor receptor(TNFR)-associated factor(TRAF)family(TRAF1–TRAF6),with the function of TRAF4 not being extensively studied in the past decade.Although numerous studies have suggested that there is elevated TRAF4 expression in human cancer,it is still unknown in which oncogenic pathway TRAF4 is mainly implicated.This review highlights TGF-β-induced SMAD-dependent signaling and non-SMAD signaling as the major pathways regulated by TRAF4 involved in breast cancer metastasis.展开更多
文摘Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.
文摘OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells.METHODS Immunohistochemistry （S-P） was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues. Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells, and uPA expression after treatment with SB203580, a specific inhibitor of p38 MAPK.RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively. The expression of p-p38 was positively related to the expression of uPA （r = 0.316, P 〈 0.05）. The expression of p-p38 and uPA was related to lymph node metastasis and the TNM stage （P 〈 0.05）, but it was not related to the patient＇s age or tumor size （P 〉 0.05）. The expression of p-p38 and uPA in MDA- MB-231 cells was higher than that in MCF-7 cells. SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression.CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression ,and it may be an important process in breast cancer invasion and metastasis.
文摘Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.
文摘Breast cancer is one of the world＇s most urgent health problems. The first symptoms of mammary malignancies are manifested only at an advanced stage with significant mortality. Detecting this disease at an early stage gives the majority of patients a better chance of survival. The aim was to search for changes in gene expression of specific tumor vascular markers like death receptor 6 （Dr6） and glycoprotein M6B （Gpm6B） in the blood of patients with breast cancer. All subjects were divided into two groups. First group with patients are with different grades of breats tumors （n = 30）. Second group consists from healthy women （n = 15）. After isolation of mRNA from blood, RT-PCR was followed by gel electrophoresis. For statistical analysis one-way ANOVA was used with Student＇s T test using GraphPad InStat software. Significant changes in mRNA levels of gene Dr6 in all grades of first stage breast cancer were detected. The mRNA levels of Dr6 showed a rising tendency from GI （116% higher value than control） to G3 （198% higher than control）. During monitoring of the mRNA level of Gpm6B, a weaker increase was observed than in Dr6. The difference in GI was only 8% higher compared with controls and 44% at G3. From our results it can be concluded that DR6 is a more suitable marker for the diagnosis of breast malignancies in the early stages than Gpm6B. In our work, a non-invasive method for more timely and precise determination of the earlier stages of breast cancer is described, which could also contribute to monitoring the effectiveness of treatment, or regression of this disease.
文摘Objective： Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inhibitors （AIs）. We aimed to study the effect on bone mineral density （BMD） and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients, for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol. Methods： One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 rag/day （n = 50） or Anastrozole 10 mg （n = 50）. Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups. Results： Use of Tamoxifen was associated with significant annual decrease in osteocalcin （P = 0.001）, whereas Anastrozole group had gradual increase of the annual levels （P 〈 0.01）. BMD decreased significantly in Anastrozole versus Tamoxifen groups （2.6% vs. 0.4%, P 〈 0.001）. Osteoporosis T 〈 -2.5 was reported significantly higher in Anastrozole group （P 〈 0.01）. Women with initial osteopenia in Anastrozole group showed significant decrease in BMD （P 〈 0.05）. The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD. Conclusion： Tamoxifen preserves BMD in postmenopausal breast cancer patients, whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy, moreover, the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.
文摘Breast cancer is a complex and heterogeneous disease with different clinical outcomes. The investigations of new biomolecular markers are essential to know the prognosis and improve the clinical management of patients. The SIRT-1 （sirtuin- 1） is a histone deacetylase implicated in various epigenetic critical functions for the cells and the maintenance of genomic stability. The objective of this study is to investigate the grade of expression of the SIRT-I （sirtuin-1） and the prognostic value in overall survival of women with breast cancer. Retrospective cohort of 457 women with breast cancer has been researched, undergoing treatment in Erechim-RS from 2003 to 2013 and followed until July 2015. The degree of SIRT-1 expression was investigated by immunohistochemistry in 123 patients （26.9%） of the cohort. The OS （overall survival） from specific disease and risk of death from breast cancer were estimated by Kaplan-Meier and Cox＇s proportional risks. The median age of 57.4 years cohort with OS of 79.6% in 5 years and 69.1% at 10 years, with follow-up time of 61.9 months are revealed in this work. The SIRT-1 overexpression was found in 6.5% of cases and characterized a subgroup of women with shorter survival and increased risk of death from breast cancer （HR = 2.66; 95% CI 1.03 to 6.86; p = 0.043） and adjusted by age （HR = 2.86; 95% CI 1.11 to 7.38; p = 0.030）, histology （HR = 2.79; 95% CI 1.07 to 7.28; p = 0.036）, lymph nodes （HR = 2.73; 95% CI 1.06 to 7.04; p = 0.037）, Her-2 （HR = 2.82; 95% CI 1.07 to 7.44; p = 0.036）; chemotherapy （HR = 2.90; 95% CI 1.11 to 7.60; p = 0.030） and radiotherapy （HR = 2.71; 95% CI 1.05 to 7.01; p = 0.040）. In regressive multivariate models adjusted for age, status of axillary lymph nodes, Her-2 expression and proliferation index （Ki-67）, the grade of expression of the SIRT-1 maintained association with poor prognosis. From the study, it can be concluded that the assessment of the SIRT-1 expression is an independent prognostic biomarker in breast cancer.
文摘Objective To screen the target gene UBE2C and explore its prognostic value and immune correlation in breast cancer(BRCA)using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO)and analyzed to obtain differentially expressed genes(DEGs).Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs.Then the key gene UBE2C was determined using R language,STRING,and Cytoscape,and the differential expression of UBE2C was verified using the external datasets,The Cancer Genome Atlas(TCGA),and quantitative real-time PCR(qRT-PCR).The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language,TIMER,and Gene Set Enrichment Analysis(GSEA).Results The expression of UBE2C was differentially upregulated in BRCA,as verified by TCGA and qRT-PCR.Prognostic analysis revealed that UBE2C served as an independent prognostic factor.High expression of UBE2C was associated with decreased immune infiltration levels of B cells,CD4+T cells,CD8+T cells,macrophages,and myeloid dendritic cells in BRCA tissue.The expression of UBE2C in BRCA showed a significant correlation with PDCD1,CD274,and CTLA4 expressions.There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability.GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues can predict the survivals and prognosis of BRCA patients.Also,it is closely related to the BRCA immune microenvironment and can predict the effecacy of immunotherapy in BRCA patients.Therefore,UBE2C may be an potential immune-related prognostic biomarker for BRCA.
基金National Natural Science Foundation of China(Grant No.81372266)Foundation of Tianjin Binhai Science and Technology Plan(Grant No.2010BK160010)
文摘Overexpression of thioredoxin reductase has been identified in a variety of primary tumors, suggesting the levels of TrxR activity between tumor patients and normal people are potentially different. Here, we performed a study to investigate the differences of TrxR activity between normal people and breast tumor patients, with the expectation that TrxR activity can be considered as a novel biomarker involved in breast cancer diagnosis and treatment. In this study, we have demonstrated for the first time that TrxR levels in breast cancer patients before therapy were significantly higher than those of normal people （P〈0.05）. No significant difference of TrxR activity was found among the patients at different stages of breast tumor progression. In the patient group of TrxR 〈10 U/mL, evaluation of TrxR activity has shown a high consistency with the results from cancer diagnostic imaging. Overall, these observations suggest TrxR as an effective biomarker to monitor and evaluate the clinical outcome of breast cancer therapeutics, and identify TrxR activity as a novel approach for breast cancer early-stage detection.
基金supported by the Zhejiang University Special Fund for Fundamental Researchthe Fundamental Research Funds for the Central Universities(R14C070002)the Netherlands Organization of Scientific Research grant(MW-NWO 918.66.606),from the Cancer Genomics Centre Netherlands and the Centre for Biomedical Genetics
文摘The tumor-promoting arm of transforming growth factor beta(TGF-β)receptor signaling contributes to advanced cancer progression and is considered a master regulator of breast cancer metastasis.In mammals,there are six distinct members in the tumor-necrosis factor receptor(TNFR)-associated factor(TRAF)family(TRAF1–TRAF6),with the function of TRAF4 not being extensively studied in the past decade.Although numerous studies have suggested that there is elevated TRAF4 expression in human cancer,it is still unknown in which oncogenic pathway TRAF4 is mainly implicated.This review highlights TGF-β-induced SMAD-dependent signaling and non-SMAD signaling as the major pathways regulated by TRAF4 involved in breast cancer metastasis.
