Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes1
BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of...
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Published in | Translational oncology Vol. 10; no. 1; pp. 99 - 107 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Neoplasia Press
22.12.2016
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Subjects | |
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Abstract | BACKGROUND:
Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed.
METHODS:
GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters.
RESULTS:
A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (
χ
2
= 30.71,
P
< .001) that exhibits better discrimination for prognosis than Lauren classification (
χ
2
= 12.11,
P
= .002). FRZB [RR (95% CI) = 1.824 (1.115-2.986),
P
= .017] and EFEMP1 [RR (95% CI) = 1.537 (0.969-2.437),
P
= .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI) = 1.616 (0.938-2.785),
P
= .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort.
CONCLUSION:
We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients. |
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AbstractList | BACKGROUND:
Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed.
METHODS:
GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters.
RESULTS:
A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (
χ
2
= 30.71,
P
< .001) that exhibits better discrimination for prognosis than Lauren classification (
χ
2
= 12.11,
P
= .002). FRZB [RR (95% CI) = 1.824 (1.115-2.986),
P
= .017] and EFEMP1 [RR (95% CI) = 1.537 (0.969-2.437),
P
= .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI) = 1.616 (0.938-2.785),
P
= .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort.
CONCLUSION:
We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients. |
Author | Shao, Linlin Cheng, Rui Guo, Shuilong Zhang, Shutian Zhao, Yu Zhu, Shengtao Qiu, Xintao Xing, Jie Min, Li |
AuthorAffiliation | Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA |
AuthorAffiliation_xml | – name: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA – name: Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – name: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China |
Author_xml | – sequence: 1 givenname: Li surname: Min fullname: Min, Li organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 2 givenname: Yu surname: Zhao fullname: Zhao, Yu organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 3 givenname: Shengtao surname: Zhu fullname: Zhu, Shengtao organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 4 givenname: Xintao surname: Qiu fullname: Qiu, Xintao organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 5 givenname: Rui surname: Cheng fullname: Cheng, Rui organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 6 givenname: Jie surname: Xing fullname: Xing, Jie organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 7 givenname: Linlin surname: Shao fullname: Shao, Linlin organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 8 givenname: Shuilong surname: Guo fullname: Guo, Shuilong email: slong.guo@163.com, slong.guo@163.com, zhangshutian@ccmu.edu.cn organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA – sequence: 9 givenname: Shutian surname: Zhang fullname: Zhang, Shutian email: zhangshutian@ccmu.edu.cn, slong.guo@163.com, zhangshutian@ccmu.edu.cn organization: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA |
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Notes | Li Min and Yu Zhao contributed equally to this work. |
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Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based... |
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Title | Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes1 |
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