scholarly journals Linc00665 Can Predict the Response to Cisplatin-Paclitaxel Neoadjuvant Chemotherapy for Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Huijuan Dai ◽  
Xiaonan Sheng ◽  
Rui Sha ◽  
Jing Peng ◽  
Fan Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Enrichment Analysis ◽  
Predictive Biomarker ◽  
Gene Set Enrichment Analysis ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Kegg Analysis

ObjectiveLinc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.Materials and MethodsThe present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.ResultsThe present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125–0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104–0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.ConclusionLinc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.

scholarly journals Diagnostic and Prognostic implications of AAGAB expression in human breast cancer

2020 ◽  
Author(s):  
Cheng Zhang ◽  
Chen Gong ◽  
Yang Liu ◽  
Changcai Wang ◽  
Cheng Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Human Breast Cancer ◽  
Univariate Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Poor Overall Survival

Abstract Background: Alpha and gamma adaptin binding protein p34 (AAGAB) was previously reported as a novel on-treatment biomarker can improve prediction of response to neoadjuvant chemotherapy in breast cancer. However, the expression and prognostic value of AAGAB in breast cancer is unknown, the function of AAGAB in breast cancer remains to be elucidated. Methods: Herein we investigated the role of AAGAB in human breast cancer from the TCGA database, immunohistochemistry, Gene set enrichment analysis (GSEA) and immune infiltration analysis. Results: Increased AABAB expression in breast cancer was significantly associated with age, gender, race, ER status, PR status, N-stage, PAM50 classification and histological type (all p-values<0.05). Kaplan-Meier survival analysis showed that breast cancer patients with AAGAB-high had a worse prognosis than that with AAGAB-low (p=0.005). Univariate analysis using logistic regression revealed that age, pathological stage, and number of lymph nodes were significantly associated with poor overall survival (OS) (all p <0.05). AAGAB expression level was significantly correlated with cell purity, CD8 T cells, macrophages, CD4 T cells and dendritic cells. Functional annotations indicated that AAGAB is involved in the most significant signaling pathways including intra Golgi traffic and peroxisomal lipid metabolism pathways. Conclusions: Our study revealed that elevated AAGAB expression was significantly correlated with aggressive progression, poor survival in breast cancer patients. AAGAB may serve as a new biomarker and potential treatment target in breast cancer.

scholarly journals Prognostic Significance of SQSTM1 in Breast Cancer: A Comprehensive Analysis

2020 ◽  
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Somatic Mutation ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Regulation Mechanism ◽  
Breast Cancer Patients ◽  
Gene Set ◽  
Multiple Datasets

Abstract Background: SQSTM1 (Sequestosome 1, p62) is degraded by activated autophagy and involved in the progression of in various types of cancers. However, the prognostic role and underlying regulation mechanism of SQSTM1 in the progression and development of breast cancer remain unclear.Methods: In this study, 1336 samples with available mRNA data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database and 27 formalin fixation and paraffin embedding (FFPE) tissue samples from the First Affiliated Hospital of Xi’an Jiaotong University were collected to evaluate SQSTM1 expression in mRNA and protein levels. Kaplan–Meier and Cox regression were used for revealing prognostic value in three independent breast cancer independent datasets. Tumor Immune Estimation Resource (TIMER) database and Gene Set Variation Analysis (GSVA) was used to explore the relationship of SQSTM1 mRNA expression and immune infiltration level in breast cancer. Dysregulation mechanisms of SQSTM1 were also explored including copy number variation (CNV), somatic mutation, epigenetic alterations and other transcription and post-transcription level using multiple datasets. Finally, Gene Set Enrichment Analysis (GSEA) was constructed to elucidate functional regulating performance of SQSTM1 in breast cancer.Results: The results showed that mRNA and protein level of SQSTM1 were significantly elevated in breast cancer and receiver operating characteristic (ROC) curve showed that p62 may act as diagnostic biomarker. Lower expression of SQSTM1 predicted better outcome through multiple datasets. It was also found that SQSTM1 correlated with immune infiltrates in breast cancer. Moreover, CNV and methylation of SQSTM1 DNA was correlated with SQSTM1 dysregulation and act as prognostic factors for breast cancer patients. Yet, somatic mutation status of SQSTM1 didn’t show any prognostic relevance. We also identified diverse transcription factors that directly bound to SQSTM1 DNA and the miRNAs which may regulate SQSTM1 mRNA. Finally, functional enrichment analysis revealed that SQSTM1 is related to cell signal transduction, oxidative stress and autophagy in breast cancer.Conclusion: Our findings revealed that SQSTM1 plays a key role in the progression of breast cancer and might be a promising biomarker for the diagnosis and personalized treatment of breast cancer patients.

Immune-related gene based prognostic signature for the risk stratification analysis of breast cancer

2021 ◽  
Vol 16 ◽  
Author(s):  
Dongqing Su ◽  
Qianzi Lu ◽  
Yi Pan ◽  
Yao Yu ◽  
Shiyuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Score Model

Background: Breast cancer has plagued women for many years and caused many deaths around the world. Method: In this study, based on the weighted correlation network analysis, univariate Cox regression analysis and least absolute shrinkage and selection operator, 12 immune-related genes were selected to construct the risk score for breast cancer patients. The multivariable Cox regression analysis, gene set enrichment analysis and nomogram were also conducted in this study. Results: Good results were obtained in the survival analysis, enrichment analysis, multivariable Cox regression analysis and immune-related feature analysis. When the risk score model was applied in 22 breast cancer cohorts, the univariate Cox regression analysis demonstrated that the risk score model was significantly associated with overall survival in most of the breast cancer cohorts. Conclusion: Based on these results, we could conclude that the proposed risk score model may be a promising method, and may improve the treatment stratification of breast cancer patients in the future work.

Plasma miR-221 as a Predictive Biomarker for Chemoresistance in Breast Cancer Patients who Previously Received Neoadjuvant Chemotherapy

Onkologie ◽  
2011 ◽  
Vol 34 (12) ◽  
pp. 675-680 ◽  
Author(s):  
Ruihua Zhao ◽  
Jiannan Wu ◽  
Weijuan Jia ◽  
Chang Gong ◽  
Fengyan Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Predictive Biomarker ◽  
Breast Cancer Patients

scholarly journals Prognostic Significance of SQSTM1 in Breast Cancer: A Comprehensive Analysis

2020 ◽  
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Somatic Mutation ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Regulation Mechanism ◽  
Breast Cancer Patients ◽  
Gene Set ◽  
Multiple Datasets

Abstract Background: SQSTM1 (Sequestosome 1, p62) is degraded by activated autophagy and involved in the progression of in various types of cancers. However, the prognostic role and underlying regulation mechanism of SQSTM1 in the progression and development of breast cancer remain unclear.Methods: In this study, 1336 samples with available mRNA data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database and 27 formalin fixation and paraffin embedding (FFPE) tissue samples from the First Affiliated Hospital of Xi’an Jiaotong University were collected to evaluate SQSTM1 expression in mRNA and protein levels. Kaplan–Meier and Cox regression were used for revealing prognostic value in three independent breast cancer independent datasets. Tumor Immune Estimation Resource (TIMER) database and Gene Set Variation Analysis (GSVA) was used to explore the relationship of SQSTM1 mRNA expression and immune infiltration level in breast cancer. Dysregulation mechanisms of SQSTM1 were also explored including copy number variation (CNV), somatic mutation, epigenetic alterations and other transcription and post-transcription level using multiple datasets. Finally, Gene Set Enrichment Analysis (GSEA) was constructed to elucidate functional regulating performance of SQSTM1 in breast cancer.Results: The results showed that mRNA and protein level of SQSTM1 were significantly elevated in breast cancer and receiver operating characteristic (ROC) curve showed that p62 may act as diagnostic biomarker. Lower expression of SQSTM1 predicted better outcome through multiple datasets. It was also found that SQSTM1 correlated with immune infiltrates in breast cancer. Moreover, CNV and methylation of SQSTM1 DNA was correlated with SQSTM1 dysregulation and act as prognostic factors for breast cancer patients. Yet, somatic mutation status of SQSTM1 didn’t show any prognostic relevance. We also identified diverse transcription factors that directly bound to SQSTM1 DNA and the miRNAs which may regulate SQSTM1 mRNA. Finally, functional enrichment analysis revealed that SQSTM1 is related to cell signal transduction, oxidative stress and autophagy in breast cancer.Conclusion: Our findings revealed that overexpression of SQSTM1 significantly to poor survival and immune infiltrations in breast cancer. In addition, SQSTM1 plays a key role in the progression of breast cancer and might be a promising biomarker for the diagnosis and personalized treatment of breast cancer patients.

scholarly journals Neoadjuvan Chemotheraphy Responses to Local Advanced Breast Cancer Patients at Dr Moh Hoesin Hospital Palembang

2020 ◽  
Vol 3 (3) ◽  
pp. 51-58
Author(s):  
Aldo Giovanno ◽  
Mgs. Irsan Saleh ◽  
Nur Qodir ◽  
Mulawan Umar
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Radical Mastectomy ◽  
Advanced Breast ◽  
Chemotherapy Response ◽  
Breast Cancer Patients

Breast cancer is a malignancy which invaded breast tissue in the form of ductal or lobular. One most therapywhich is given is neoadjuvant chemotherapy. Neoadjuvant Chemotherapy can reduce tumor size so that surgerycan be performed with good breast removal with Modification of Radical Mastectomy (MRM) and BreastConservative Therapy (BCT). This purpose from this research is to find out neoadjuvant chemotherapy response inLocally Advanced Breast Cancer Patients which has received chemotherapy treatment in RSUP dr MohammadHoesin Palembang. This observational descriptive study was conducted at RSUP Mohammad Hoesin Palembang inthe period between October until November 2019. The sample of this study was locally advanced breast Cancerpatients who underwent chemotherapy that met the inclusion and exclusion criteria. The data were obtained byinterviews and observed medical records from the patients which were then analyzed by univariate analysis usingSPSS version 25. In this study there were 34 locally advanced breast cancer patients who fulfilled the inclusion andexclusion criteria. 24 of 34 patients (70,6%) received positive response and 10 of 34 patients (29,4%) receivednegative response.

Impact of pre-treatment lymphocyte monocyte ratio and neutrophil lymphocyte ratio on pathologic response in breast cancer patients receiving neoadjuvant chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12623-e12623
Author(s):  
Osama Mosalem ◽  
Saud Alsubait ◽  
Shouq Kherallah ◽  
Venumadhavi Gogineni ◽  
Ling Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
The Mean ◽  
Pre Treatment

e12623 Background: Hematologic markers have been looked at as potential prognostic biomarkers in a variety of cancers. Ni and colleagues (2014) have shown that an elevated pre-treatment lymphocyte-to-monocyte ratio (LMR) was significantly associated with improved disease-free survival (DFS) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NACT). Given the prognostic implications of hematologic inflammatory parameters, we sought to understand if such biomarkers will predict response to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Methods: We conducted a retrospective review of breast cancer patients treated with NACT at our institution (2008-2018). Data on patient characteristics, stage, pathologic characteristics, and blood counts were collected. Blood parameters prior to NACT were used to calculate LMR and neutrophil-to-lymphocyte ratio (NLR). To test the impact of LMR and NLR on pathologic response, a two sample mean test was used first as univariate analysis. Next, logistic regression was employed for multivariate analysis controlling for patient characteristics with interaction of LMR and NLR with ER, PR and HER2 status. Results: A total of 50 patients were included. 38% of patients achieved a pathologic complete response (pCR). The mean LMR was 3.69 (1.4-12.5), and the mean NLR was 2.55 (0.66 – 9.31). On univariate analysis, a high NLR was associated with a higher likelihood of achieving a pCR (OR = 1.64, 95% CI = 1.01-2.63). A high LMR was associated with a higher likelihood of pCR; however, this was not statistically significant (OR = 1.08, 95% CI = 0.78-1.47). On multivariate analysis, patients with HER-2 positive disease with a high LMR had a significantly higher chance of having a pCR (OR = 1.72, 95% CI = 1.06-2.78). Conclusions: Our study showed that NLR was a predictor of pCR in breast cancer patients receiving neoadjuvant chemotherapy. A high NLR was associated with achieving a pCR on univariate analysis. Multivariate analysis suggested that HER-2 positive disease with a high LMR had a significantly higher chance of achieving a pCR. The results of this cohort correlate with previous reports by others showing that pre-NACT LMR and NLR provide prognostic information in patients with breast cancer. Although limited by sample size, this adds to the growing body of literature supporting peripheral blood counts as a biomarker for outcomes in breast cancer.

scholarly journals Improving breast cancer sensitivity to paclitaxel by increasing aneuploidy

2019 ◽  
Vol 116 (47) ◽  
pp. 23691-23697 ◽  
Author(s):  
Sylvie Rodrigues-Ferreira ◽  
Anne Nehlig ◽  
Hadia Moindjie ◽  
Clarisse Monchecourt ◽  
Cynthia Seiler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Microtubule Assembly ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Multipolar Spindle ◽  
Mitotic Abnormalities

Predictive biomarkers for tumor response to neoadjuvant chemotherapy are needed in breast cancer. This study investigates the predictive value of 280 genes encoding proteins that regulate microtubule assembly and function. By analyzing 3 independent multicenter randomized cohorts of breast cancer patients, we identified 17 genes that are differentially regulated in tumors achieving pathological complete response (pCR) to neoadjuvant chemotherapy. We focused on the MTUS1 gene, whose major product, ATIP3, is a microtubule-associated protein down-regulated in aggressive breast tumors. We show here that low levels of ATIP3 are associated with an increased pCR rate, pointing to ATIP3 as a predictive biomarker of breast tumor chemosensitivity. Using preclinical models of patient-derived xenografts and 3-dimensional models of breast cancer cell lines, we show that low ATIP3 levels sensitize tumors to the effects of taxanes but not DNA-damaging agents. ATIP3 silencing improves the proapoptotic effects of paclitaxel and induces mitotic abnormalities, including centrosome amplification and multipolar spindle formation, which results in chromosome missegregation leading to aneuploidy. As shown by time-lapse video microscopy, ATIP3 depletion exacerbates cytokinesis failure and mitotic death induced by low doses of paclitaxel. Our results favor a mechanism by which the combination of ATIP3 deficiency and paclitaxel treatment induces excessive aneuploidy, which in turn results in elevated cell death. Together, these studies highlight ATIP3 as an important regulator of mitotic integrity and a useful predictive biomarker for a population of chemoresistant breast cancer patients.

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