Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods
Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression d...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/5/1271 |
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| author | Rafat Ali Armiya Sultan Romana Ishrat Shafiul Haque Nida Jamil Khan Miguel Angel Prieto |
| author_facet | Rafat Ali Armiya Sultan Romana Ishrat Shafiul Haque Nida Jamil Khan Miguel Angel Prieto |
| author_sort | Rafat Ali |
| collection | DOAJ |
| description | Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression datasets are widely used to discover the new biomarkers and molecular therapeutic targets in diseases. In the present study, we analyzed four datasets using R packages with accession number GSE29044, GSE42568, GSE89116, and GSE109169 retrieved from NCBI-GEO and differential expressed genes (DEGs) were identified. Protein–protein interaction (PPI) network was constructed to screen the key genes. Subsequently, the GO function and KEGG pathways were analyzed to determine the biological function of key genes. Expression profile of key genes was validated in MCF-7 and MDA-MB-231 human breast cancer cell lines using qRT-PCR. Overall expression level and stage wise expression pattern of key genes was determined by GEPIA. The bc-GenExMiner was used to compare expression level of genes among groups of patients with respect to age factor. OncoLnc was used to analyze the effect of expression levels of <i>LAMA2</i>, <i>TIMP4</i>, and <i>TMTC1</i> on the survival of breast cancer patients. We identified nine key genes, of which COL11A1, MMP11, and COL10A1 were found up-regulated and PCOLCE2, <i>LAMA2</i>, <i>TMTC1</i>, ADAMTS5, <i>TIMP4</i>, and RSPO3 were found down-regulated. Similar expression pattern of seven among nine genes (except ADAMTS5 and RSPO3) was observed in MCF-7 and MDA-MB-231 cells. Further, we found that <i>LAMA2</i>, <i>TMTC1</i>, and <i>TIMP4</i> were significantly expressed among different age groups of patients. <i>LAMA2</i> and <i>TIMP4</i> were found significantly associated and <i>TMTC1</i> was found less correlated with breast cancer occurrence. We found that the expression level of <i>LAMA2</i>, <i>TIMP4</i>, and <i>TMTC1</i> was abnormal in all TCGA tumors and significantly associated with poor survival. |
| first_indexed | 2024-03-11T03:55:26Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:55:26Z |
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| spelling | doaj.art-24894bd9cdb942b69093a92dd8101a032023-11-18T00:34:32ZengMDPI AGBiomedicines2227-90592023-04-01115127110.3390/biomedicines11051271Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro MethodsRafat Ali0Armiya Sultan1Romana Ishrat2Shafiul Haque3Nida Jamil Khan4Miguel Angel Prieto5Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi 110025, IndiaDepartment of Biosciences, Jamia Millia Islamia (A Central University), New Delhi 110025, IndiaCenter for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University), New Delhi 110025, IndiaResearch and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Biosciences, Jamia Millia Islamia (A Central University), New Delhi 110025, IndiaNutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, Universidade de Vigo, E32004 Ourense, SpainBreast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression datasets are widely used to discover the new biomarkers and molecular therapeutic targets in diseases. In the present study, we analyzed four datasets using R packages with accession number GSE29044, GSE42568, GSE89116, and GSE109169 retrieved from NCBI-GEO and differential expressed genes (DEGs) were identified. Protein–protein interaction (PPI) network was constructed to screen the key genes. Subsequently, the GO function and KEGG pathways were analyzed to determine the biological function of key genes. Expression profile of key genes was validated in MCF-7 and MDA-MB-231 human breast cancer cell lines using qRT-PCR. Overall expression level and stage wise expression pattern of key genes was determined by GEPIA. The bc-GenExMiner was used to compare expression level of genes among groups of patients with respect to age factor. OncoLnc was used to analyze the effect of expression levels of <i>LAMA2</i>, <i>TIMP4</i>, and <i>TMTC1</i> on the survival of breast cancer patients. We identified nine key genes, of which COL11A1, MMP11, and COL10A1 were found up-regulated and PCOLCE2, <i>LAMA2</i>, <i>TMTC1</i>, ADAMTS5, <i>TIMP4</i>, and RSPO3 were found down-regulated. Similar expression pattern of seven among nine genes (except ADAMTS5 and RSPO3) was observed in MCF-7 and MDA-MB-231 cells. Further, we found that <i>LAMA2</i>, <i>TMTC1</i>, and <i>TIMP4</i> were significantly expressed among different age groups of patients. <i>LAMA2</i> and <i>TIMP4</i> were found significantly associated and <i>TMTC1</i> was found less correlated with breast cancer occurrence. We found that the expression level of <i>LAMA2</i>, <i>TIMP4</i>, and <i>TMTC1</i> was abnormal in all TCGA tumors and significantly associated with poor survival.https://www.mdpi.com/2227-9059/11/5/1271breast cancerdifferentially expressed genesdown regulated genespoor survivalup regulated genes |
| spellingShingle | Rafat Ali Armiya Sultan Romana Ishrat Shafiul Haque Nida Jamil Khan Miguel Angel Prieto Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods Biomedicines breast cancer differentially expressed genes down regulated genes poor survival up regulated genes |
| title | Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods |
| title_full | Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods |
| title_fullStr | Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods |
| title_full_unstemmed | Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods |
| title_short | Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods |
| title_sort | identification of new key genes and their association with breast cancer occurrence and poor survival using in silico and in vitro methods |
| topic | breast cancer differentially expressed genes down regulated genes poor survival up regulated genes |
| url | https://www.mdpi.com/2227-9059/11/5/1271 |
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