Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer
Objective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution of hypoxia-related heterogeneity in PDAC remains unclear. Methods: Spatial transcri...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2021-05-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1864 |
| _version_ | 1818649736435990528 |
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| author | Huizhi Sun Danfang Zhang Chongbiao Huang Yuhong Guo Zhao Yang Nan Yao Xueyi Dong Runfen Cheng Nan Zhao Jie Meng Baocun Sun Jihui Hao |
| author_facet | Huizhi Sun Danfang Zhang Chongbiao Huang Yuhong Guo Zhao Yang Nan Yao Xueyi Dong Runfen Cheng Nan Zhao Jie Meng Baocun Sun Jihui Hao |
| author_sort | Huizhi Sun |
| collection | DOAJ |
| description | Objective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution of hypoxia-related heterogeneity in PDAC remains unclear. Methods: Spatial transcriptomics (STs), a new technique, was used to investigate the ST features of engrafted human PDAC in the ischemic hind limbs of nude mice. Transcriptomes from ST spots in the hypoxic tumor and the control were clustered using differentially-expressed genes. These data were compared to determine the spatial organization of hypoxia-induced heterogeneity in PDAC. Clinical relevance was validated using the Tumor Cancer Genome Atlas and KM-plotter databases. The CMAP website was used to identify molecules that may serve as therapeutic targets for PDAC. Results: ST showed that the tumor cell subgroups decreased to 7 subgroups in the hypoxia group, compared to 9 subgroups in the control group. Different subgroups showed positional characteristics and different gene signatures. Subgroup 6 located at the invasive front showed a higher proliferative ability under hypoxia. Subgroup 6 had active functions including cell proliferation, invasion, and response to stress. Expressions of hypoxia-related genes, LDHA, TPI1, and ENO1, induced changes. CMAP analysis indicated that ADZ-6482, a PI3K inhibitor, was targeted by the invasive subgroup in hypoxic tumors. Conclusions: This study is the first to describe hypoxic microenvironment-induced spatial transcriptome changes in PDAC, and to identify potential treatment targets for PDAC. These data will provide the basis for further investigations of the prognoses and treatments of hypoxic tumors. |
| first_indexed | 2024-12-17T01:39:04Z |
| format | Article |
| id | doaj.art-ed1ddd0f573e437d87dea544786c4cfc |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-12-17T01:39:04Z |
| publishDate | 2021-05-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-ed1ddd0f573e437d87dea544786c4cfc2022-12-21T22:08:23ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412021-05-0118261663010.20892/j.issn.2095-3941.2021.0158Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancerHuizhi Sun0Danfang Zhang1Chongbiao Huang2Yuhong Guo3Zhao Yang4Nan Yao5Xueyi Dong6Runfen Cheng7Nan Zhao8Jie Meng9Baocun Sun10Jihui Hao11Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Pathology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaObjective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution of hypoxia-related heterogeneity in PDAC remains unclear. Methods: Spatial transcriptomics (STs), a new technique, was used to investigate the ST features of engrafted human PDAC in the ischemic hind limbs of nude mice. Transcriptomes from ST spots in the hypoxic tumor and the control were clustered using differentially-expressed genes. These data were compared to determine the spatial organization of hypoxia-induced heterogeneity in PDAC. Clinical relevance was validated using the Tumor Cancer Genome Atlas and KM-plotter databases. The CMAP website was used to identify molecules that may serve as therapeutic targets for PDAC. Results: ST showed that the tumor cell subgroups decreased to 7 subgroups in the hypoxia group, compared to 9 subgroups in the control group. Different subgroups showed positional characteristics and different gene signatures. Subgroup 6 located at the invasive front showed a higher proliferative ability under hypoxia. Subgroup 6 had active functions including cell proliferation, invasion, and response to stress. Expressions of hypoxia-related genes, LDHA, TPI1, and ENO1, induced changes. CMAP analysis indicated that ADZ-6482, a PI3K inhibitor, was targeted by the invasive subgroup in hypoxic tumors. Conclusions: This study is the first to describe hypoxic microenvironment-induced spatial transcriptome changes in PDAC, and to identify potential treatment targets for PDAC. These data will provide the basis for further investigations of the prognoses and treatments of hypoxic tumors.http://www.cancerbiomed.org/index.php/cocr/article/view/1864pancreatic cancerhypoxiaspatial transcriptomic |
| spellingShingle | Huizhi Sun Danfang Zhang Chongbiao Huang Yuhong Guo Zhao Yang Nan Yao Xueyi Dong Runfen Cheng Nan Zhao Jie Meng Baocun Sun Jihui Hao Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer Cancer Biology & Medicine pancreatic cancer hypoxia spatial transcriptomic |
| title | Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer |
| title_full | Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer |
| title_fullStr | Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer |
| title_full_unstemmed | Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer |
| title_short | Hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer |
| title_sort | hypoxic microenvironment induced spatial transcriptome changes in pancreatic cancer |
| topic | pancreatic cancer hypoxia spatial transcriptomic |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1864 |
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