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pmid:33036243

High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection.

Masanori Oshi · Stephanie Newman · Yoshihisa Tokumaru · Li Yan · Ryusei Matsuyama · Itaru Endo · Matthew H G Katz · Kazuaki Takabe

Cancers · 2020 doi:10.3390/cancers12102871

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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pmid:33036243
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title
High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection.
doi
10.3390/cancers12102871
pmid
33036243
authors array · 8 items
[0]
Masanori Oshi
[1]
Stephanie Newman
[2]
Yoshihisa Tokumaru
[3]
Li Yan
[4]
Ryusei Matsuyama
[5]
Itaru Endo
[6]
Matthew H G Katz
[7]
Kazuaki Takabe
journal
Cancers
year
2020
abstract
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 MKI67 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 KRAS and TP53 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.
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sections[16] "4.5. Statistical Analysis" paragraph 2
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For uni- and multi-variate analysis, Cox proportional hazard analyses were used to estimate HR, 95% CI, and p-value.
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sections[12] "4.1. Pancreatic Cancer Cohorts and Their Data" paragraph 2
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Transcriptomic profiling and clinical information of the TCGA pancreatic cancer (TCGA_PAAD) was downloaded from the Genomic Data Commons Data Portal (GDC).
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Epigenome analysis of male identical twin pairs discordant for sexual orientation, age 21 to 55.
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Development of a prognostic gene signature in pancreatic cancer
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Microarray gene-expression profiles of 69 pancreatic tumors and 61 adjacent non-tumor tissue from patients with pancreatic ductal adenocarcinoma
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Clinical characteristics of the low and high G2M score pancreatic cancer patients in The Cancer Genome Atlas (TCGA) cohort.
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2.3. Clinical Characteristics of the High G2M Pathway Score Pancreatic Cancer Patients
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Table 1
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Clinical characteristics of the low and high G2M score pancreatic cancer patients in The Cancer Genome Atlas (TCGA) cohort.
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42 (47.7%)
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11 (12.5%)
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71 (80.7%)
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13 (14.8%)
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4 (4.5%)
[3]
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[3]
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46 (52.3%)
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30 (34.1%)
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75 (85.3%)
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1 (1.1%)
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0 (0.0%)
[3]
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[2]
[3]
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N−
[1]
26 (29.5%)
[2]
23 (26.1%)
[3]
0.612
[32] array · 4 items
[0]
N+
[1]
58 (65.9%)
[2]
64 (72.7%)
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[0]
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[1]
4 (4.6%)
[2]
1 (1.1%)
[3]
[34] array · 4 items
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AJCC M-category
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[2]
[3]
[35] array · 4 items
[0]
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[1]
37 (42.0%)
[2]
41 (46.6%)
[3]
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[36] array · 4 items
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[1]
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[2]
2 (2.3%)
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[1]
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45 (51.1%)
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[1]
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[1]
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[2]
1 (1.1%)
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[44] array · 4 items
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[1]
[2]
[3]
[45] array · 4 items
[0]
Resection status
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[2]
[3]
0.102
[46] array · 4 items
[0]
R0
[1]
57 (64.8%)
[2]
48 (54.6%)
[3]
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R1/2
[1]
23 (26.1%)
[2]
34 (38.6%)
[3]
[48] array · 4 items
[0]
Unknown
[1]
8 (9.1%)
[2]
6 (6.8%)
[3]
locator
section[5]/table-wrap[1]#cancers-12-02871-t001
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Survival analyses of the G2M pathway score and other factors in the TCGA cohort.
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pmcid
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section_index
9
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2.7. High G2M Pathway Score Pancreatic Tumors were Significantly Associated with Worse Survival in Pathologically Margin-Positive Resection (R1 or R2), but not in Margin-Negative Resection (R0)
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12
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Table 2
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Survival analyses of the G2M pathway score and other factors in the TCGA cohort.
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[0] array · 3 items
[0]
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[1]
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[1] array · 4 items
[0]
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[1]
p-Value
[2]
HR (95% CI)
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[0]
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[1]
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[4]
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0.126
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1.93 (0.96–3.86)
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[10] array · 5 items
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1.58 (0.96–2.61)
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section[9]/table-wrap[1]#cancers-12-02871-t002
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For uni- and multi-variate analysis, Cox proportional hazard analyses were used to estimate HR, 95% CI, and p-value.
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Automated Assays Laravel application and simulated adapters
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GSE28746
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GSE62452
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GSE28746
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Transcriptomic profiling and clinical information of the TCGA pancreatic cancer (TCGA_PAAD) was downloaded from the Genomic Data Commons Data Portal (GDC).
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The paper names GSE62452, GSE57495, GSE28746 in Gene Expression Omnibus (GEO) repository of the US National Institutes of Health and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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minimax
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33036243", "kind": "science-record", "revision": 8, "content_hash": "sha256:e2e98e5db995ed96a2dc4af47dc8f6237c97028c2ac5ec1d2853221f8d97a0cb", "created_at": "2026-11-01T15:41:12Z", "updated_at": "2026-11-01T22:02:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection.", "doi": "10.3390/cancers12102871", "pmid": "33036243", "authors": ["Masanori Oshi", "Stephanie Newman", "Yoshihisa Tokumaru", "Li Yan", "Ryusei Matsuyama", "Itaru Endo", "Matthew H G Katz", "Kazuaki Takabe"], "journal": "Cancers", "year": 2020, "abstract": "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 MKI67 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 KRAS and TP53 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. 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