scholarly journals Identifying Biomarkers to Predict the Progression and Prognosis of Breast Cancer by Weighted Gene Co-expression Network Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Gengsheng Shi ◽  
Zhenru Shen ◽  
Yi Liu ◽  
Wenqin Yin
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Division ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
Hub Genes ◽  
Poor Overall Survival ◽  
Ki 67 ◽  
Free Survival

Breast cancer (BC) is the leading cause of cancer death among women worldwide. The molecular mechanisms of its pathogenesis are still to be investigated. In our study, differentially expressed genes (DEGs) were screened between BC and normal tissues. Based on the DEGs, a weighted gene co-expression network analysis (WGCNA) was performed in 683 BC samples, and eight co-expressed gene modules were identified. In addition, by relating the eight co-expressed modules to clinical information, we found the blue module and pathological stage had a significant correlation (r = 0.24, p = 1e–10). Validated by multiple independent datasets, using one-way ANOVA, survival analysis and expression level revalidation, we finally screened 12 hub genes that can predict BC progression and prognosis. Functional annotation analysis indicated that the hub genes were enriched in cell division and cell cycle regulation. Importantly, higher expression of the 12 hub genes indicated poor overall survival, recurrence-free survival, and disease-free survival in BC patients. In addition, the expression of the 12 hub genes showed a significantly positive correlation with the expression of cell proliferation marker Ki-67 in BC. In summary, our study has identified 12 hub genes associated with the progression and prognosis of BC; these hub genes might lead to poor outcomes by regulating the cell division and cell cycle. These hub genes may serve as a biomarker and help to distinguish different pathological stages for BC patients.

scholarly journals Identification of four genes and biological characteristics of esophageal squamous cell carcinoma by integrated bioinformatics analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yexun Song ◽  
Xianyao Wang ◽  
Fengjun Wang ◽  
Xiaowei Peng ◽  
Peiyu Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
Hub Genes ◽  
Free Survival ◽  
Disease Free

Abstract Background Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated. Methods The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein–protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR). Results In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival. Conclusions SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.

scholarly journals Relationship between Ribosomal Protein S6-pS240 Expression and other Prognostic Factors in Non-Special Type Invasive Breast Cancer

Breast Care ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 171-175
Author(s):  
Frederik Cuperjani ◽  
Lumturije Gashi ◽  
Fisnik Kurshumliu ◽  
Shemsedin Dreshaj ◽  
Fitim Selimi
Keyword(s):  
Breast Cancer ◽  
Ribosomal Protein ◽  
Invasive Breast Cancer ◽  
Menopausal Status ◽  
Treatment Protocol ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free

Background: The aim of this study was to investigate the immunohistochemical expression of ribosomal protein (RP) S6-pS240 in non-special type invasive breast cancer in relation to other prognostic markers and gain new insights to facilitate more individualized treatment. Methods: The following clinical and histopathological parameters of 120 patients were determined: S6-pS240 expression, age, menopausal status, tumor size and grade, TNM stage, Nottingham Prognostic Index (NPI), lymph node stage, estrogen and progesterone receptor (ER/PR) expression, HER2/neu amplification, lymphovascular invasion, and proliferative index as measured by Ki-67. Treatment protocol and disease-free survival were evaluated accordingly. Results: Significant positive correlations were seen between S6-pS240 expression and Ki-67 values (rho = 0.530, p < 0.001), and NPI (rho = 0.370, p < 0.001) and HER2/neu amplification (rho = 0.368, p < 0.001). A negative correlation was found between S6-pS240 and ER/PR expression (rho = 0.362, p < 0.001). Patients with negative RP S6-pS240 expression had significantly longer disease-free survival (log-rank test, p = 0.005). Conclusion: Immunohistochemical analysis of RP S6-pS240 is a valuable additional prognostic marker in patients with invasive breast cancer. Routine use of S6-pS240 immunohistochemistry is recommended.

scholarly journals Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Shengjie Sun ◽  
Huiyu Dong ◽  
Tao Yan ◽  
Junchen Li ◽  
Chao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Gynecological Cancer ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Poor Overall Survival ◽  
Free Survival ◽  
The Impact

Abstract Background Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers . We performed this meta-analysis to clarify the preliminary predictive value of TSP-1. Methods Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratio s ( HRs ) with 95% confidence intervals ( CIs ) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. Results A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival ( OS ) (HR=1.40, 95% CI: 1.17~1.68). However, high TSP-1 expression predicted no significant impact on progression-free survival ( PFS )/ metastasis-free survival (MFS ) (HR=1.35, 95%CI: 0.87-2.10) and disease-free survival ( DFS )/ recurrence-free survival ( RFS ) (HR = 1.40, 95%CI: 0.77–2.53). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Conclusions Our findings indicated high TSP-1 expression may serve as a promising biomarker of poor prognosis and novel therapeutic target in cancers, especially in breast cancer and gynecological cancer.

scholarly journals Bioinformatic Identification of Potential Hub Genes in Muscle-Invasive Bladder Urothelial Carcinoma

2020 ◽  
Vol 29 ◽  
pp. 096368972096517
Author(s):  
Changgang Guo ◽  
Ting Shao ◽  
Dadong Wei ◽  
Chunsheng Li ◽  
Fengjun Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Hub Genes ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Bladder Urothelial Carcinoma ◽  
Muscle Invasive

Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.

scholarly journals Lysophosphatidic acid receptor 6 regulated by miR-27a-3p attenuates tumor proliferation in breast cancer

2021 ◽  
Author(s):  
J. Lei ◽  
S. Guo ◽  
K. Li ◽  
J. Tian ◽  
B. Zong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Lysophosphatidic Acid ◽  
Ectopic Expression ◽  
Disease Free Survival ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Lpa Receptor

Abstract Purpose Lysophosphatidic acid (LPA) is a bioactive molecule which participates in many physical and pathological processes. Although LPA receptor 6 (LPAR6), the last identified LPA receptor, has been reported to have diverse effects in multiple cancers, including breast cancer, its effects and functioning mechanisms are not fully known. Methods Multiple public databases were used to investigate the mRNA expression of LPAR6, its prognostic value, and potential mechanisms in breast cancer. Western blotting was performed to validate the differential expression of LPAR6 in breast cancer tissues and their adjacent tissues. Furthermore, in vitro experiments were used to explore the effects of LPAR6 on breast cancer. Additionally, TargetScan and miRWalk were used to identify potential upstream regulating miRNAs and validated the relationship between miR-27a-3p and LPAR6 via real-time polymerase chain reaction and an in vitro rescue assay. Results LPAR6 was significantly downregulated in breast cancer at transcriptional and translational levels. Decreased LPAR6 expression in breast cancer is significantly correlated with poor overall survival, disease-free survival, and distal metastasis-free survival, particularly for hormone receptor-positive patients, regardless of lymph node metastatic status. In vitro gain and loss-of-function assays indicated that LPAR6 attenuated breast cancer cell proliferation. The analyses of TCGA and METABRIC datasets revealed that LPAR6 may regulate the cell cycle signal pathway. Furthermore, the expression of LPAR6 could be positively regulated by miR-27a-3p. The knockdown of miR-27a-3p increased cell proliferation, and ectopic expression of LPAR6 could partly rescue this phenotype. Conclusion LPAR6 acts as a tumor suppressor in breast cancer and is positively regulated by miR-27a-3p.

scholarly journals Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Shengjie Sun ◽  
Huiyu Dong ◽  
Tao Yan ◽  
Junchen Li ◽  
Bianjiang Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Gynecological Cancer ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Poor Overall Survival ◽  
Free Survival ◽  
The Impact

Abstract Background Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers. We performed this meta-analysis to illustrate the preliminary predictive value of TSP-1. Methods Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. Results A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival (OS) (HR=1.40, 95% CI: 1.17~1.68; P＜0.001). However, high TSP-1 expression predicted no significant impact on progression-free survival (PFS)/ metastasis-free survival (MFS) (HR=1.35, 95%CI: 0.87-2.10; P=0.176) and disease-free survival (DFS)/ recurrence-free survival (RFS) (HR = 1.40, 95%CI: 0.77–2.53; P=0.271). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Additionally, the relatively small number of studies on PFS/MFS and DFS/RFS is a limitation. The data extracted through Kaplan-Meier curves may not be accurate. Moreover, only English articles were included in this article, which may lead to deviations in the results.Conclusions Our findings indicated high TSP-1 expression may act as a promising biomarker of poor prognosis in cancers, especially in breast cancer and gynecological cancer.

scholarly journals Evaluation of the Prognostic Value of Ki-67 in Early Stage Breast Cancer

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 15-15
Author(s):  
Soheir S. Ismail ◽  
Amr L. Farag ◽  
Diaa Eldin M. Sherif ◽  
Ibrahim S. Alhussini
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Progesterone Receptors ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Ki67 Index ◽  
Ki 67 ◽  
Free Survival ◽  
Prognostic Effect ◽  
Disease Free

Background: Breast cancer is a disease which have a variety of important features whose different phenotype only partially summarize the underlying biological complexity. Treatment choices in routine management principally rely on the clinical and pathological characteristics of the disease, although molecular classification currently offers information alongside that provided by clinical and pathological examination. The decision to offer adjuvant chemotherapy to patients is not easy and the knowledge of prognostic factors is mandatory. Ki 67 plays an important role in this context, especially in patients who do not have access to genetic signatures. Aim of the work: This study aims to evaluate the value of Ki67 as a prognostic factor in relation to disease free survival and other clinico-pathological factors in Egyptian females with early stage breast cancer. Patients and Methods: Type of study: This is a retrospective cohort study. Study population: It consisted of 124 patients diagnosed with early stage breast cancer. Study Period: They were diagnosed between January 2011 and December 2015. Study setting: The patients were following up in Ain Shams University Hospital clinical oncology department. Information were manually retrieved from the records of the clinical oncology department at Ain Shams university hospitals. Clinical and pathological tumor characteristics were collected using patient charts and pathology reports. Results: Our study showed a significant relation between Ki67 index and estrogen receptors, progesterone receptors and Her2 neu status. Ki67 was found to be statistically significantly correlated to intrinsic subtypes. Our study was unable to find out the effect of Ki67 on disease free survival. Cox regression analysis revealed a statistical significant influence of estrogen receptors status on disease free survival. It also revealed statistical prognostic effect of progesterone receptors and Her2 status on disease free survival. Covariate analysis of results in our study showed that tumor with T4 stage has a significant prognostic effect on disease free survival. Conclusion: ki67 index may have a prognostic role in management of early stage breast cancer in relation to other prognostic markers like hormone receptor status and HER2neu expression. Moreover, immunohisto-chemistry-based subtyping is extremely important to classify breast carcinoma into molecular subtypes that vary in clinic-pathological features and would lead to different prognosis. Thus, molecular subtyping is essential for breast carcinoma management.

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