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

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Oct 10

PMID 33036243

Citations 43

Authors

Masanori Oshi

Stephanie Newman

Yoshihisa Tokumaru

Li Yan

Ryusei Matsuyama

Itaru Endo

Matthew H G Katz

Kazuaki Takabe

Affiliations

Soon will be listed here.

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 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 and 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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