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

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.

SUBMITTER: Oshi M

PROVIDER: S-EPMC7599494 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Oshi Masanori M Newman Stephanie S Tokumaru Yoshihisa Y Yan Li L Matsuyama Ryusei R Endo Itaru I Katz Matthew H G MHG Takabe Kazuaki K

Cancers 20201006 10

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 ...[more]

PMID: 33036243

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Project description:BackgroundA margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM.MethodsA total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching.ResultsThe R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival.ConclusionsThe R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era.

Dataset Information

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

Publications

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

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