Oshi Masanori, Newman Stephanie, Tokumaru Yoshihisa, Yan Li, Matsuyama Ryusei, Endo Itaru, Katz Matthew H G, Takabe Kazuaki
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cancers (Basel). 2020 Oct 6;12(10):2871. doi: 10.3390/cancers12102871.
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.
由于细胞增殖失控，胰腺癌的致死率很高。G2M 检查点通路是细胞周期的重要组成部分。我们假设，高 G2M 通路评分与胰腺癌患者的细胞增殖及较差的生存率相关。使用 Hallmark G2M 检查点基因集进行基因集变异分析，以此作为评分，对来自 3 个队列（TCGA、GSE62452、GSE57495）的总共 390 名人类胰腺癌患者进行分析。高 G2M 评分的肿瘤富集了其他细胞增殖基因集以及表达、病理分级和增殖评分。独立于其他预后因素，G2M 评分可预测胰腺癌患者的疾病特异性生存。高 G2M 肿瘤与 和 的高突变率相关，并显著富集这些通路基因集，以及 Th2 细胞的高浸润。高 G2M 评分在 3 个队列中始终与较差的总生存率相关，尤其是在 R1/2 切除的患者中，但在 R0 切除的患者中并非如此。与 R0 相比，R1/2 切除的高 G2M 肿瘤高度富集代谢和细胞成分的基因集。据我们所知，这是第一项使用基因集变异分析作为评分来研究 G2M 通路在胰腺癌中的临床相关性的研究。
