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

被引：54

作者：

Oshi, Masanori ^{[1
,2
]}

Newman, Stephanie ^{[2
,3
]}

Tokumaru, Yoshihisa ^{[2
,4
]}

Yan, Li ^{[5
]}

Matsuyama, Ryusei ^{[1
]}

Endo, Itaru ^{[1
]}

Katz, Matthew H. G. ^{[6
]}

Takabe, Kazuaki ^{[1
,2
,3
,7
,8
,9
]}

机构：

[1] Yokohama City Univ, Grad Sch Med, Dept Gastroenterol Surg, Yokohama, Kanagawa 2360004, Japan

[2] Roswell Park Comprehens Canc Ctr, Dept Surg Oncol, Breast Surg, Buffalo, NY 14263 USA

[3] SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Dept Surg, Buffalo, NY 14263 USA

[4] Gifu Univ, Grad Sch Med, Dept Surg Oncol, 1-1 Yanagido, Gifu 5011194, Japan

[5] Roswell Park Comprehens Canc Ctr, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[7] Niigata Univ, Grad Sch Med & Dent Sci, Div Digest & Gen Surg, Niigata 9518520, Japan

[8] Fukushima Med Univ, Sch Med, Dept Breast Surg, Fukushima 9601295, Japan

[9] Tokyo Med Univ, Dept Breast Surg & Oncol, Tokyo 1608402, Japan

来源：

CANCERS | 2020年 / 12卷 / 10期

基金：

美国国家卫生研究院;

关键词：

biomarker; cell cycle; gene set; pathway analysis; pancreatic cancer; tumor gene expression; LONG-TERM SURVIVORS; EXPRESSION; IMPACT; IDENTIFICATION; CHEMOTHERAPY; LANDSCAPE; KINASE; TP53; KRAS;

D O I：

10.3390/cancers12102871

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary The G2M checkpoint pathway is a critical step in the cell cycle, which is one of the hallmarks in cancer. We investigated clinical relevance of the G2M pathway in pancreatic cancer, using gene set variation analysis (GSVA) with Hallmark G2M checkpoint gene set. High G2M score tumors enriched several cell proliferation gene sets as well as MKI67 expression, pathological grade, and proliferation score. Furthermore, the 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 multiple cohorts, particularly in R1/2 resection, but not in R0. 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.

引用

页码：1 / 18

页数：17

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