scholarly journals Circular RNA hsa_circ_0005046 and hsa_circ_0001791 May Become Diagnostic Biomarkers for Breast Cancer Early Detection

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Peili Zhang ◽  
Zhigui Zuo ◽  
Wenjing Shang ◽  
Aihua Wu ◽  
Ruichun Bi ◽  
...  

Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.


2021 ◽  
Author(s):  
Yongjie Li ◽  
Min Zeng ◽  
Ting Wang ◽  
Feng Jiang

Abstract Background Pancreatic cancer is a malignant tumor of digestive system with high fatality rate, and its prognosis is very poor. Type Ⅴ collagen α3 (COL5A3) is highly expressed in a variety of tumor tissues, but its prognostic value and immune infiltration in pancreatic cancer are still unclear. Therefore, we evaluated the prognostic role of COL5A3 in pancreatic cancer and its correlation with immune infiltration. Methods The transcriptional expression profiles of COL5A3 in pancreatic cancer and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). In the GEO (Gene expression omnibus) dataset (GSE16515), we compared the expression of COL5A3 in normal and tumor tissues. The expression of COL5A3 protein was evaluated by the human protein atlas (THPA). The effect of COL5A3 on survival was evaluated by Kaplan-Meier method. Receiver operating characteristic (ROC) curve was used to distinguish pancreatic cancer from paracancerous normal tissues. Protein-protein interaction (PPI) network was constructed by the STRING. Use the "ClusterProfiler" package for functional enrichment analysis. Tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were used to determine the relationship between COL5A3mRNA expression and immune infiltration. Results Compared with normal tissues, COL5A3 is highly expressed in pancreatic cancer tissues. The high expression of COL5A3 is related to the poor clinicopathological features and poor prognosis of pancreatic cancer. Kaplan-Meier survival analysis showed that the prognosis of pancreatic cancer patients with high expression of COL5A3 was worse than that of patients with low expression of COL5A3. ROC curve shows that COL5A3 has high sensitivity and specificity in the diagnosis of pancreatic cancer. Correlation analysis showed that the expression of COL5A3mRNA was related to immune cell infiltration. Conclusion This study reveals for the first time that COL5A3 may be a new prognostic biomarker related to immune infiltration and provide a new target for the diagnosis and treatment of pancreatic cancer.


2020 ◽  
Vol 19 ◽  
pp. 153303382096074
Author(s):  
Xiaohan Li ◽  
Fang Ma ◽  
Ligang Wu ◽  
Xu Zhang ◽  
Jinhai Tian ◽  
...  

Background: To study the specific expression of circular RNA (circRNA) in breast cancer and adjacent normal tissues to identify differentially expressed circRNA in breast cancer patients. To study the correlation between circRNA and clinical data of breast cancer, and to evaluate its potential as a breast cancer biomarker. Methods: The differential expression of circRNAs between the breast cancer tissues and adjacent normal tissues was screened by Human CircRNA Microarray. Candidate circRNAs verified by qRT-PCR. CircRNA was analyzed by Agilent GeneSpring 13.0 software. SPSS23.0, GraphPad Prism, and Sigmaplot software were used for statistical analysis. Perform T test, one-way ANOVA, curve regression analysis and ROC curve analysis for evaluating the diagnostic value of circular RNA. Results: Among the 2021 differentially expressed circRNAs, 546 were up-regulated and 1475 were down-regulated in breast cancer tissues. The validation study demonstrated that six circRNAs were downregulated. Among them, hsa_circ_0104824 proved high correlation between breast cancer tissues and plasma samples in its expression and diagnostic value. Conclusion: Hsa_circ_0104824 may serve as a promising predictive biomarker and therapeutic target for patients with breast cancer.


2021 ◽  
Author(s):  
Shuai Wang ◽  
Guo-Tian Ruan ◽  
Yi-Zhen Gong ◽  
Cun Liao ◽  
Lei Zhang ◽  
...  

Abstract Background: The diagnostic and prognostic value of HEPACAM family member 2 (HEPACAM2) gene in patients with colon adenocarcinoma (COAD) is rarely reported. Therefore, the purpose of this study is to explore the diagnostic and prognostic value of HEPACAM2 gene in patients with COAD.Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value analysis from different databases. Secondly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. Finally, utilizing joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes.Results: Differential analyses of multiple databases showed that the HEPACAM2 expression level in COAD tumor tissue was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a higher diagnostic value in COAD. The RT-qPCR verification results of COAD tissue in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissue was significantly higher than that of adjacent normal tissues (P<0.001), and the diagnostic value was high in COAD (AUC=0.892). The prognostic value analysis showed that low expression of HEPACAM2 gene had a poorer prognosis of overall survival (OS) in patients with COAD when compared with those patients with high expression of HEPACAM2 gene ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better prognosis of overall COAD OS.Conclusion: The results of this study suggested that the HEPACAM2 may be an independent diagnostic and prognostic biomarker for COAD.


2021 ◽  
Author(s):  
Yongjie Li ◽  
Min Zeng ◽  
Ting Wang ◽  
Feng Jiang

Abstract Pancreatic cancer is a malignant tumor of digestive system with high fatality rate, and its prognosis is very poor. Type Ⅴ collagen α3 (COL5A3) is highly expressed in a variety of tumor tissues, but its prognostic value and immune infiltration in pancreatic cancer are still unclear. Therefore, we evaluated the prognostic role of COL5A3 in pancreatic cancer and its correlation with immune infiltration. The transcriptional expression profiles of COL5A3 in pancreatic cancer and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). In the GEO (Gene expression omnibus) dataset (GSE16515), we compared the expression of COL5A3 in normal and tumor tissues. The expression of COL5A3 protein was evaluated by the human protein atlas (THPA). The effect of COL5A3 on survival was evaluated by Kaplan-Meier method. Receiver operating characteristic (ROC) curve was used to distinguish pancreatic cancer from paracancerous normal tissues. Protein-protein interaction (PPI) network was constructed by the STRING. Use the "ClusterProfiler" package for functional enrichment analysis. Tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were used to determine the relationship between COL5A3 mRNA expression and immune infiltration. Compared with normal tissues, COL5A3 is highly expressed in pancreatic cancer tissues. The high expression of COL5A3 is related to the poor clinicopathological features and poor prognosis of pancreatic cancer. Kaplan-Meier survival analysis showed that the prognosis of pancreatic cancer patients with high expression of COL5A3 was worse than that of patients with low expression of COL5A3. ROC curve shows that COL5A3 has high sensitivity and specificity in the diagnosis of pancreatic cancer. Correlation analysis showed that the expression of COL5A3 mRNA was related to immune cell infiltration. This study reveals for the first time that COL5A3 may be a new prognostic biomarker related to immune infiltration and provide a new target for the diagnosis and treatment of pancreatic cancer.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8403 ◽  
Author(s):  
Yue Li ◽  
Xiaoyan Zhou ◽  
Jiali Liu ◽  
Yang Yin ◽  
Xiaohong Yuan ◽  
...  

Background BRCA1 and BRCA2 genes are currently proven to be closely related to high lifetime risks of breast cancer. To date, the closely related genes to BRCA1/2 mutations in breast cancer remains to be fully elucidated. This study aims to identify the gene expression profiles and interaction networks influenced by BRCA1/2 mutations, so as to reflect underlying disease mechanisms and provide new biomarkers for breast cancer diagnosis or prognosis. Methods Gene expression profiles from The Cancer Genome Atlas (TCGA) database were downloaded and combined with cBioPortal website to identify exact breast cancer patients with BRCA1/2 mutations. Gene set enrichment analysis (GSEA) was used to analyze some enriched pathways and biological processes associated BRCA mutations. For BRCA1/2-mutant breast cancer, wild-type breast cancer and corresponding normal tissues, three independent differentially expressed genes (DEGs) analysis were performed to validate potential hub genes with each other. Protein–protein interaction (PPI) networks, survival analysis and diagnostic value assessment helped identify key genes associated with BRCA1/2 mutations. Results The regulation process of cell cycle was significantly enriched in mutant group compared with wild-type group. A total of 294 genes were identified after analysis of DEGs between mutant patients and wild-type patients. Interestingly, by the other two comparisons, we identified 43 overlapping genes that not only significantly expressed in wild-type breast cancer patients relative to normal tissues, but more significantly expressed in BRCA1/2-mutant breast patients. Based on the STRING database and cytoscape software, we constructed a PPI network using 294 DEGs. Through topological analysis scores of the PPI network and 43 overlapping genes, we sought to select some genes, thereby using survival analysis and diagnostic value assessment to identify key genes pertaining to BRCA1/2-mutant breast cancer. CCNE1, NPBWR1, A2ML1, EXO1 and TTK displayed good prognostic/diagnostic value for breast cancer and BRCA1/2-mutant breast cancer. Conclusion Our research provides comprehensive and new insights for the identification of biomarkers connected with BRCA mutations, availing diagnosis and treatment of breast cancer and BRCA1/2-mutant breast cancer patients.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sepideh Mehrpour Layeghi ◽  
Maedeh Arabpour ◽  
Abbas Shakoori ◽  
Mohammad Mehdi Naghizadeh ◽  
Yaser Mansoori ◽  
...  

Abstract Background Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes. Methods A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real‐time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC. Results According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein–protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis. Conclusions Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.


Breast Cancer ◽  
2021 ◽  
Author(s):  
Xuemin Liu ◽  
Qingyu Chang ◽  
Haiqiang Wang ◽  
Hairong Qian ◽  
Yikun Jiang

Abstract Background MicroRNA-155 (miR-155) may function as a diagnostic biomarker of breast cancer (BC). Nevertheless, the available evidence is controversial. Therefore, we performed this study to summarize the global predicting role of miR-155 for early detection of BC and preliminarily explore the functional roles of miR-155 in BC. Methods We first collected published studies and applied the bivariate meta-analysis model to generate the pooled diagnostic parameters of miR-155 in diagnosing BC such as sensitivity, specificity and area under curve (AUC). Then, we applied function enrichment and protein–protein interactions (PPI) analyses to explore the potential mechanisms of miR-155. Results A total of 21 studies were finally included. The results indicated that miR-155 allowed for the discrimination between BC patients and healthy controls with a sensitivity of 0.87 (95% CI 0.78–0.93), specificity of 0.82 (0.72–0.89), and AUC of 0.91 (0.88–0.93). In addition, the overall sensitivity, specificity and AUC for circulating miR-155 were 0.88 (0.76–0.95), 0.83 (0.72–0.90), and 0.92 (0.89–0.94), respectively. Function enrichment analysis revealed several vital ontologies terms and pathways associated with BC occurrence and development. Furthermore, in the PPI network, ten hub genes and two significant modules were identified to be involved in some important pathways associated with the pathogenesis of BC. Conclusions We demonstrated that miR-155 has great potential to facilitate accurate BC detection and may serve as a promising diagnostic biomarker for BC. However, well-designed cohort studies and biological experiments should be implemented to confirm the diagnostic value of miR-155 before it can be applied to routine clinical procedures.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.


2021 ◽  
Vol 22 (4) ◽  
pp. 1820
Author(s):  
Anna Makuch-Kocka ◽  
Janusz Kocki ◽  
Anna Brzozowska ◽  
Jacek Bogucki ◽  
Przemysław Kołodziej ◽  
...  

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.


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