A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma
There is an increase in the incidence of early onset colorectal carcinoma (EOCRC). To better understand if there is any difference in molecular pathogenesis of EOCRC and late onset colorectal carcinoma (LOCRC), we compared the clinical, histological, transcriptome, and methylome profile of paired CR...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14261 |
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| author | Muhammad G Kibriya Maruf Raza Anthony Quinn Mohammed Kamal Habibul Ahsan Farzana Jasmine |
| author_facet | Muhammad G Kibriya Maruf Raza Anthony Quinn Mohammed Kamal Habibul Ahsan Farzana Jasmine |
| author_sort | Muhammad G Kibriya |
| collection | DOAJ |
| description | There is an increase in the incidence of early onset colorectal carcinoma (EOCRC). To better understand if there is any difference in molecular pathogenesis of EOCRC and late onset colorectal carcinoma (LOCRC), we compared the clinical, histological, transcriptome, and methylome profile of paired CRC and healthy colonic tissue from 67 EOCRC and 98 LOCRC patients. The frequency of stage 3 CRC, lymph node involvement, lymphovascular invasion, and perineural invasion was higher in the EOCRC group. Many of the cancer related pathways were differentially expressed in CRC tissue in both EOCRC and LOCRC patients. However, the magnitude of differential expression for some groups of genes, such as DNA damage repair genes and replication stress genes, were significantly less pronounced in the EOCRC group, suggesting less efficient DNA damage repair to be associated with EOCRC. A more marked methylation of “growth factor receptor” genes in LOCRC correlated with a more pronounced down-regulation of those genes in that group. From a therapeutic point of view, more over-expression of fatty acid synthase (<i>FASN</i>) among the LOCRC patients may suggest a better response of <i>FASN</i> targeted therapy in that group. The age of onset of CRC did not appear to modify the response of cis-platin or certain immune checkpoint inhibitors. We found some differences in the molecular pathogenesis in EOCRC and LOCRC that may have some biological and therapeutic significance. |
| first_indexed | 2024-03-09T18:16:53Z |
| format | Article |
| id | doaj.art-a02c14b521de451c9213db9760504abf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:16:53Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a02c14b521de451c9213db9760504abf2023-11-24T08:41:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221426110.3390/ijms232214261A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal CarcinomaMuhammad G Kibriya0Maruf Raza1Anthony Quinn2Mohammed Kamal3Habibul Ahsan4Farzana Jasmine5Institute for Population and Precision Health (IPPH), Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USADepartment of Pathology, Jahurul Islam Medical College, Kishoregonj 2336, BangladeshInstitute for Population and Precision Health (IPPH), Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USADepartment of Pathology, The Laboratory Dhaka, Dhaka 1205, BangladeshInstitute for Population and Precision Health (IPPH), Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health (IPPH), Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USAThere is an increase in the incidence of early onset colorectal carcinoma (EOCRC). To better understand if there is any difference in molecular pathogenesis of EOCRC and late onset colorectal carcinoma (LOCRC), we compared the clinical, histological, transcriptome, and methylome profile of paired CRC and healthy colonic tissue from 67 EOCRC and 98 LOCRC patients. The frequency of stage 3 CRC, lymph node involvement, lymphovascular invasion, and perineural invasion was higher in the EOCRC group. Many of the cancer related pathways were differentially expressed in CRC tissue in both EOCRC and LOCRC patients. However, the magnitude of differential expression for some groups of genes, such as DNA damage repair genes and replication stress genes, were significantly less pronounced in the EOCRC group, suggesting less efficient DNA damage repair to be associated with EOCRC. A more marked methylation of “growth factor receptor” genes in LOCRC correlated with a more pronounced down-regulation of those genes in that group. From a therapeutic point of view, more over-expression of fatty acid synthase (<i>FASN</i>) among the LOCRC patients may suggest a better response of <i>FASN</i> targeted therapy in that group. The age of onset of CRC did not appear to modify the response of cis-platin or certain immune checkpoint inhibitors. We found some differences in the molecular pathogenesis in EOCRC and LOCRC that may have some biological and therapeutic significance.https://www.mdpi.com/1422-0067/23/22/14261colorectal carcinomaearly onset CRCmulti-omicslymphovascular invasionperineural invasionDNA damage repair |
| spellingShingle | Muhammad G Kibriya Maruf Raza Anthony Quinn Mohammed Kamal Habibul Ahsan Farzana Jasmine A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma International Journal of Molecular Sciences colorectal carcinoma early onset CRC multi-omics lymphovascular invasion perineural invasion DNA damage repair |
| title | A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma |
| title_full | A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma |
| title_fullStr | A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma |
| title_full_unstemmed | A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma |
| title_short | A Transcriptome and Methylome Study Comparing Tissues of Early and Late Onset Colorectal Carcinoma |
| title_sort | transcriptome and methylome study comparing tissues of early and late onset colorectal carcinoma |
| topic | colorectal carcinoma early onset CRC multi-omics lymphovascular invasion perineural invasion DNA damage repair |
| url | https://www.mdpi.com/1422-0067/23/22/14261 |
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