Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy
Abstract Background Molecular heterogeneity is one of the most important concerns in colorectal cancer (CRC), which results in a wide range of therapy responses and patient prognosis. We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and dru...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-022-02694-9 |
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| author | Ebrahim Salehitabar Mohammad Mahdevar Ali Valipour Motlagh Farzad Seyed Forootan Sara Feizbakhshan Dina Zohrabi Maryam Peymani |
| author_facet | Ebrahim Salehitabar Mohammad Mahdevar Ali Valipour Motlagh Farzad Seyed Forootan Sara Feizbakhshan Dina Zohrabi Maryam Peymani |
| author_sort | Ebrahim Salehitabar |
| collection | DOAJ |
| description | Abstract Background Molecular heterogeneity is one of the most important concerns in colorectal cancer (CRC), which results in a wide range of therapy responses and patient prognosis. We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and drug resistance. Methods Two cohort studies, the cancer genome atlas (TCGA) and the GSE39582, were used to discover oncogenes genes with HHE. The relationship between identified genes with clinical and genomic characteristics was evaluated based on TCGA data. Also, the GDSC and CCLE data were used for drug resistance and sensitivity. Sixty CRC samples were used to validate the obtained data by RT-qPCR. Results Findings revealed that 132 genes with HHE were found to be up-regulated in both cohorts and were enriched in pathways such as hypoxia, angiogenesis, and metastasis. Forty-nine of selected genes related to clinical and genomic variables, including stage, common mutations, the tumor site, and microsatellite state that were ignored. The expression level of CXCL1, SFTA2, SELE, and SACS as genes with HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and SACS had HHE in CRC samples. The expression of many identified genes like BGN, MMP7, COL11A1, FAP, KLK10, and TNFRSE11B was associated with resistance to chemotherapy drugs. Conclusions Some genes expression, including SELE, SACS, BGN, KLK10, COL11A1, and TNFRSE11B have an oncogenic function with HHE, and their expression can be used as indicators for differing treatment responses and survival rates in CRC. |
| first_indexed | 2024-04-12T05:13:55Z |
| format | Article |
| id | doaj.art-726571224e6545c5ba7c5806503dafe4 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-12T05:13:55Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-726571224e6545c5ba7c5806503dafe42022-12-22T03:46:41ZengBMCCancer Cell International1475-28672022-09-0122111210.1186/s12935-022-02694-9Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategyEbrahim Salehitabar0Mohammad Mahdevar1Ali Valipour Motlagh2Farzad Seyed Forootan3Sara Feizbakhshan4Dina Zohrabi5Maryam Peymani6Department of Biology, Faculty of Science, NourDanesh Institute of Higher EducationCellular, Molecular and Genetics Research Center, Isfahan University of Medical SciencesDepartment of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad UniversityMedical Genetics Research Center of Genome, Isfahan University of Medical SciencesCellular, Molecular and Genetics Research Center, Isfahan University of Medical SciencesDepartment of Biology, Faculty of Science, NourDanesh Institute of Higher EducationDepartment of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad UniversityAbstract Background Molecular heterogeneity is one of the most important concerns in colorectal cancer (CRC), which results in a wide range of therapy responses and patient prognosis. We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and drug resistance. Methods Two cohort studies, the cancer genome atlas (TCGA) and the GSE39582, were used to discover oncogenes genes with HHE. The relationship between identified genes with clinical and genomic characteristics was evaluated based on TCGA data. Also, the GDSC and CCLE data were used for drug resistance and sensitivity. Sixty CRC samples were used to validate the obtained data by RT-qPCR. Results Findings revealed that 132 genes with HHE were found to be up-regulated in both cohorts and were enriched in pathways such as hypoxia, angiogenesis, and metastasis. Forty-nine of selected genes related to clinical and genomic variables, including stage, common mutations, the tumor site, and microsatellite state that were ignored. The expression level of CXCL1, SFTA2, SELE, and SACS as genes with HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and SACS had HHE in CRC samples. The expression of many identified genes like BGN, MMP7, COL11A1, FAP, KLK10, and TNFRSE11B was associated with resistance to chemotherapy drugs. Conclusions Some genes expression, including SELE, SACS, BGN, KLK10, COL11A1, and TNFRSE11B have an oncogenic function with HHE, and their expression can be used as indicators for differing treatment responses and survival rates in CRC.https://doi.org/10.1186/s12935-022-02694-9High heterogeneityTumor sampleMutationGene expressionCancer treatment |
| spellingShingle | Ebrahim Salehitabar Mohammad Mahdevar Ali Valipour Motlagh Farzad Seyed Forootan Sara Feizbakhshan Dina Zohrabi Maryam Peymani Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy Cancer Cell International High heterogeneity Tumor sample Mutation Gene expression Cancer treatment |
| title | Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy |
| title_full | Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy |
| title_fullStr | Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy |
| title_full_unstemmed | Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy |
| title_short | Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy |
| title_sort | identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer a challenge and a strategy |
| topic | High heterogeneity Tumor sample Mutation Gene expression Cancer treatment |
| url | https://doi.org/10.1186/s12935-022-02694-9 |
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