Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma
Abstract Background Surgical resection followed by indicated adjuvant therapy offers potential curative treatment in colonic adenocarcinoma. Beyond the well-established seed and soil theory of colon cancer progression, the 'normal-appearing' tissues near the tumor are not genuinely normal...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11595-7 |
| _version_ | 1797397923814703104 |
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| author | Tharathorn Suwatthanarak Pariyada Tanjak Thanawat Suwatthanarak Onchira Acharayothin Kullanist Thanormjit Amphun Chaiboonchoe Thikhamporn Tawantanakorn Chainarong Phalanusitthepha Atthaphorn Trakarnsanga Asada Methasate Manop Pithukpakorn Ryuichi Okamoto Vitoon Chinswangwatanakul |
| author_facet | Tharathorn Suwatthanarak Pariyada Tanjak Thanawat Suwatthanarak Onchira Acharayothin Kullanist Thanormjit Amphun Chaiboonchoe Thikhamporn Tawantanakorn Chainarong Phalanusitthepha Atthaphorn Trakarnsanga Asada Methasate Manop Pithukpakorn Ryuichi Okamoto Vitoon Chinswangwatanakul |
| author_sort | Tharathorn Suwatthanarak |
| collection | DOAJ |
| description | Abstract Background Surgical resection followed by indicated adjuvant therapy offers potential curative treatment in colonic adenocarcinoma. Beyond the well-established seed and soil theory of colon cancer progression, the 'normal-appearing' tissues near the tumor are not genuinely normal and remain as remnants in patients following surgery. Our objective was to elucidate the alteration of gene expression and pathways across various distances of resection margins in right-sided colonic adenocarcinoma. Methods Twenty-seven fresh samples of primary cancer and 56 matched non-tumor tissues adjacent to the tumor (NAT) were collected from patients with resectable right-sided colon cancer. NAT were systematically obtained at varying distances (1, 5, and 10 cm) on both proximal and distal sides. Comprehensive gene expression analysis was performed using 770-gene PanCancer Progression Panel, delineating distinctive pathways and functional predictions for each region. Results Distinctive gene signatures and pathways exhibited by normal-appearing tissues were discovered at varying distances from cancer. Notably, SFRP2, PTGDS, COL1A1, IL1B, THBS2, PTGIS, COL1A2, NPR1, and BGN were upregulated, while ENPEP, MMP1, and NRCAM were downregulated significantly in 1-cm tissue compared to farther distances. Substantial alterations in the extracellular matrix (ECM) and prostaglandin/thromboxane synthesis were significantly evident at the 1-cm distance. Functional analysis indicated enhanced cell viability and survival, alongside reduced cellular death and apoptosis. Conclusions Different distances exerted a significant impact on gene alteration within the normal-looking mucosa surrounding primary cancer, influenced by various mechanisms. These findings may highlight potential therapeutic targets related to the ECM and prostaglandin/thromboxane pathways for treatment strategies. |
| first_indexed | 2024-03-09T01:17:13Z |
| format | Article |
| id | doaj.art-078075f7548e41da9f7661cc74a690ac |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-09T01:17:13Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-078075f7548e41da9f7661cc74a690ac2023-12-10T12:22:00ZengBMCBMC Cancer1471-24072023-12-0123111410.1186/s12885-023-11595-7Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinomaTharathorn Suwatthanarak0Pariyada Tanjak1Thanawat Suwatthanarak2Onchira Acharayothin3Kullanist Thanormjit4Amphun Chaiboonchoe5Thikhamporn Tawantanakorn6Chainarong Phalanusitthepha7Atthaphorn Trakarnsanga8Asada Methasate9Manop Pithukpakorn10Ryuichi Okamoto11Vitoon Chinswangwatanakul12Graduate School of Medical and Dental Sciences, Joint Degree Doctoral Program in Medical Sciences between Tokyo Medical and Dental UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence for Systems Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Medical Genetics, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental UniversityDivision of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityAbstract Background Surgical resection followed by indicated adjuvant therapy offers potential curative treatment in colonic adenocarcinoma. Beyond the well-established seed and soil theory of colon cancer progression, the 'normal-appearing' tissues near the tumor are not genuinely normal and remain as remnants in patients following surgery. Our objective was to elucidate the alteration of gene expression and pathways across various distances of resection margins in right-sided colonic adenocarcinoma. Methods Twenty-seven fresh samples of primary cancer and 56 matched non-tumor tissues adjacent to the tumor (NAT) were collected from patients with resectable right-sided colon cancer. NAT were systematically obtained at varying distances (1, 5, and 10 cm) on both proximal and distal sides. Comprehensive gene expression analysis was performed using 770-gene PanCancer Progression Panel, delineating distinctive pathways and functional predictions for each region. Results Distinctive gene signatures and pathways exhibited by normal-appearing tissues were discovered at varying distances from cancer. Notably, SFRP2, PTGDS, COL1A1, IL1B, THBS2, PTGIS, COL1A2, NPR1, and BGN were upregulated, while ENPEP, MMP1, and NRCAM were downregulated significantly in 1-cm tissue compared to farther distances. Substantial alterations in the extracellular matrix (ECM) and prostaglandin/thromboxane synthesis were significantly evident at the 1-cm distance. Functional analysis indicated enhanced cell viability and survival, alongside reduced cellular death and apoptosis. Conclusions Different distances exerted a significant impact on gene alteration within the normal-looking mucosa surrounding primary cancer, influenced by various mechanisms. These findings may highlight potential therapeutic targets related to the ECM and prostaglandin/thromboxane pathways for treatment strategies.https://doi.org/10.1186/s12885-023-11595-7Different gene expressionNon-tumor tissues adjacent to the tumorSurgical resection marginRight-sided colonic adenocarcinomaRNA analysis |
| spellingShingle | Tharathorn Suwatthanarak Pariyada Tanjak Thanawat Suwatthanarak Onchira Acharayothin Kullanist Thanormjit Amphun Chaiboonchoe Thikhamporn Tawantanakorn Chainarong Phalanusitthepha Atthaphorn Trakarnsanga Asada Methasate Manop Pithukpakorn Ryuichi Okamoto Vitoon Chinswangwatanakul Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma BMC Cancer Different gene expression Non-tumor tissues adjacent to the tumor Surgical resection margin Right-sided colonic adenocarcinoma RNA analysis |
| title | Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma |
| title_full | Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma |
| title_fullStr | Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma |
| title_full_unstemmed | Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma |
| title_short | Exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right-sided colonic adenocarcinoma |
| title_sort | exploring extracellular matrix and prostaglandin pathway alterations across varying resection margin distances of right sided colonic adenocarcinoma |
| topic | Different gene expression Non-tumor tissues adjacent to the tumor Surgical resection margin Right-sided colonic adenocarcinoma RNA analysis |
| url | https://doi.org/10.1186/s12885-023-11595-7 |
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