Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites

Abstract Numerous reports have highlighted distinct clinical and biological characteristics between right-sided and left-sided colon cancers. Despite this research on commonalities and divergences among colorectal cancers (CRC) at different locations remain sparse. In order to elucidate gene express...

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Main Authors: Yuqi Luo, Yiwen Huang, Yanbo Luo, Yating Yin, Peter Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10528-7
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author Yuqi Luo
Yiwen Huang
Yanbo Luo
Yating Yin
Peter Wang
author_facet Yuqi Luo
Yiwen Huang
Yanbo Luo
Yating Yin
Peter Wang
author_sort Yuqi Luo
collection DOAJ
description Abstract Numerous reports have highlighted distinct clinical and biological characteristics between right-sided and left-sided colon cancers. Despite this research on commonalities and divergences among colorectal cancers (CRC) at different locations remain sparse. In order to elucidate gene expression disparities across various intestinal regions in CRC, we sourced several data series from the Gene Expression Omnibus (GEO) database. We isolated 344 tumor and 54 normal cases spanning seven locations: sigmoid, ascending, caecum, rectum, transverse, descending, and recto-sigmoid. Cell biological functions were assessed utilizing CCK8, EdU assays, Transwell assays, and wound healing assays. We identified location-related differentially expressed genes (DEGs) and their functional enrichment. TNFSF4 exhibited variances between the transverse and descending regions, allowing for discrimination of tumor tissues across four locations (sigmoid, ascending, caecum, and descending) via immune cells. Moreover, we identified 16 hub genes that collectively indicate commonality among the seven different tissue origins. Furthermore, 6 location-related genes, including DCBLD2, GTF3A, GSS, PDK1, TEAD3 and EGR2 were identified for targeted interventions. In vitro experiments indicated that increased GZMB and decreased IER3 reduced CRC cell proliferation, migration, and invasion. In summary, 16 hub genes and 6 location-related genes enhance our understanding of the potential molecular mechanisms underlying CRC spatial heterogeneity. Furthermore, GZMB and IER3 might be potential targets for CRC therapy.
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spelling doaj-art-10477c69eea047a683eafa1c78de040c2025-08-20T03:42:22ZengNature PortfolioScientific Reports2045-23222025-07-0115112210.1038/s41598-025-10528-7Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sitesYuqi Luo0Yiwen Huang1Yanbo Luo2Yating Yin3Peter Wang4Department of Gastrointestinal and Hepatobiliary Surgery, Shenzhen Longhua Distric Central HospitalDepartment of Emergency, Guangzhou First People’s HospitalDepartment of Gastrointestinal and Hepatobiliary Surgery, Shenzhen Longhua Distric Central HospitalBeijing Zhongwei Medical Research CenterBeijing Zhongwei Medical Research CenterAbstract Numerous reports have highlighted distinct clinical and biological characteristics between right-sided and left-sided colon cancers. Despite this research on commonalities and divergences among colorectal cancers (CRC) at different locations remain sparse. In order to elucidate gene expression disparities across various intestinal regions in CRC, we sourced several data series from the Gene Expression Omnibus (GEO) database. We isolated 344 tumor and 54 normal cases spanning seven locations: sigmoid, ascending, caecum, rectum, transverse, descending, and recto-sigmoid. Cell biological functions were assessed utilizing CCK8, EdU assays, Transwell assays, and wound healing assays. We identified location-related differentially expressed genes (DEGs) and their functional enrichment. TNFSF4 exhibited variances between the transverse and descending regions, allowing for discrimination of tumor tissues across four locations (sigmoid, ascending, caecum, and descending) via immune cells. Moreover, we identified 16 hub genes that collectively indicate commonality among the seven different tissue origins. Furthermore, 6 location-related genes, including DCBLD2, GTF3A, GSS, PDK1, TEAD3 and EGR2 were identified for targeted interventions. In vitro experiments indicated that increased GZMB and decreased IER3 reduced CRC cell proliferation, migration, and invasion. In summary, 16 hub genes and 6 location-related genes enhance our understanding of the potential molecular mechanisms underlying CRC spatial heterogeneity. Furthermore, GZMB and IER3 might be potential targets for CRC therapy.https://doi.org/10.1038/s41598-025-10528-7Colorectal cancerLocationBioinformaticsTFImmunology
spellingShingle Yuqi Luo
Yiwen Huang
Yanbo Luo
Yating Yin
Peter Wang
Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
Scientific Reports
Colorectal cancer
Location
Bioinformatics
TF
Immunology
title Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
title_full Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
title_fullStr Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
title_full_unstemmed Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
title_short Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
title_sort identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites
topic Colorectal cancer
Location
Bioinformatics
TF
Immunology
url https://doi.org/10.1038/s41598-025-10528-7
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AT yanboluo identificationofheterogeneityandcommoncharacteristicsincolorectalcarcinomalocatedindistinctsites
AT yatingyin identificationofheterogeneityandcommoncharacteristicsincolorectalcarcinomalocatedindistinctsites
AT peterwang identificationofheterogeneityandcommoncharacteristicsincolorectalcarcinomalocatedindistinctsites