High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection
Pancreatic cancer is highly mortal due to uncontrolled cell proliferation. The G2M checkpoint pathway is an essential part of the cell cycle. We hypothesized that a high G2M pathway score is associated with cell proliferation and worse survival in pancreatic cancer patients. Gene set variation analy...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/10/2871 |
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| author | Masanori Oshi Stephanie Newman Yoshihisa Tokumaru Li Yan Ryusei Matsuyama Itaru Endo Matthew H. G. Katz Kazuaki Takabe |
| author_facet | Masanori Oshi Stephanie Newman Yoshihisa Tokumaru Li Yan Ryusei Matsuyama Itaru Endo Matthew H. G. Katz Kazuaki Takabe |
| author_sort | Masanori Oshi |
| collection | DOAJ |
| description | Pancreatic cancer is highly mortal due to uncontrolled cell proliferation. The G2M checkpoint pathway is an essential part of the cell cycle. We hypothesized that a high G2M pathway score is associated with cell proliferation and worse survival in pancreatic cancer patients. Gene set variation analysis using the Hallmark G2M checkpoint gene set was used as a score to analyze a total of 390 human pancreatic cancer patients from 3 cohorts (TCGA, GSE62452, GSE57495). High G2M score tumors enriched other cell proliferation genes sets as well as <i>MKI67</i> expression, pathological grade, and proliferation score. Independent of other prognostic factors, G2M score was predictive of disease-specific survival in pancreatic cancer. High G2M tumor was associated with high mutation rate of <i>KRAS</i> and <i>TP53</i> and significantly enriched these pathway gene sets, as well as high infiltration of Th2 cells. High G2M score consistently associated with worse overall survival in 3 cohorts, particularly in R1/2 resection, but not in R0. High G2M tumor in R1/2 highly enriched metabolic and cellular components’ gene sets compared to R0. To our knowledge, this is the first study to use gene set variation analysis as a score to examine the clinical relevancy of the G2M pathway in pancreatic cancer. |
| first_indexed | 2024-03-10T15:48:32Z |
| format | Article |
| id | doaj.art-2c8afecbc0e944b598ba2350214049ee |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:48:32Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2c8afecbc0e944b598ba2350214049ee2023-11-20T16:12:40ZengMDPI AGCancers2072-66942020-10-011210287110.3390/cancers12102871High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) ResectionMasanori Oshi0Stephanie Newman1Yoshihisa Tokumaru2Li Yan3Ryusei Matsuyama4Itaru Endo5Matthew H. G. Katz6Kazuaki Takabe7Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanBreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USABreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanPancreatic cancer is highly mortal due to uncontrolled cell proliferation. The G2M checkpoint pathway is an essential part of the cell cycle. We hypothesized that a high G2M pathway score is associated with cell proliferation and worse survival in pancreatic cancer patients. Gene set variation analysis using the Hallmark G2M checkpoint gene set was used as a score to analyze a total of 390 human pancreatic cancer patients from 3 cohorts (TCGA, GSE62452, GSE57495). High G2M score tumors enriched other cell proliferation genes sets as well as <i>MKI67</i> expression, pathological grade, and proliferation score. Independent of other prognostic factors, G2M score was predictive of disease-specific survival in pancreatic cancer. High G2M tumor was associated with high mutation rate of <i>KRAS</i> and <i>TP53</i> and significantly enriched these pathway gene sets, as well as high infiltration of Th2 cells. High G2M score consistently associated with worse overall survival in 3 cohorts, particularly in R1/2 resection, but not in R0. High G2M tumor in R1/2 highly enriched metabolic and cellular components’ gene sets compared to R0. To our knowledge, this is the first study to use gene set variation analysis as a score to examine the clinical relevancy of the G2M pathway in pancreatic cancer.https://www.mdpi.com/2072-6694/12/10/2871biomarkercell cyclegene setpathway analysispancreatic cancertumor gene expression |
| spellingShingle | Masanori Oshi Stephanie Newman Yoshihisa Tokumaru Li Yan Ryusei Matsuyama Itaru Endo Matthew H. G. Katz Kazuaki Takabe High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection Cancers biomarker cell cycle gene set pathway analysis pancreatic cancer tumor gene expression |
| title | High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection |
| title_full | High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection |
| title_fullStr | High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection |
| title_full_unstemmed | High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection |
| title_short | High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection |
| title_sort | high g2m pathway score pancreatic cancer is associated with worse survival particularly after margin positive r1 or r2 resection |
| topic | biomarker cell cycle gene set pathway analysis pancreatic cancer tumor gene expression |
| url | https://www.mdpi.com/2072-6694/12/10/2871 |
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