High ARHGEF2 (GEF-H1) Expression is Associated with Poor Prognosis Via Cell Cycle Regulation in Patients with Pancreatic Cancer
| Autor: | Yuya Okamoto, Katsunori Imai, Noriko Yasuda-Yoshihara, Naoki Umezaki, Hirohisa Okabe, Yosuke Nakao, Yoko Ogata, Kohei Yamashita, Hideo Baba, Tatsunori Miyata, Toshihiko Yusa, Yo-ichi Yamashita, Shigeki Nakagawa, Hiromitsu Hayashi, Rumi Itoyama |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Cell cycle checkpoint 03 medical and health sciences 0302 clinical medicine Surgical oncology Pancreatic cancer Internal medicine medicine Humans Cell Proliferation Cell growth business.industry Hazard ratio Cell Cycle Checkpoints Cell cycle Prognosis medicine.disease Immunohistochemistry Cell Cycle Gene Pancreatic Neoplasms 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology Surgery business Rho Guanine Nucleotide Exchange Factors |
| Zdroj: | Annals of Surgical Oncology. 28:4733-4743 |
| ISSN: | 1534-4681 1068-9265 |
| Popis: | Pancreatic cancer has an extremely poor prognosis, even after curative resection. Treatment options for pancreatic cancer remain limited, therefore new therapeutic targets are urgently needed. We searched for genes predictive of poor prognosis in pancreatic cancer using a public database and validated the survival impact of the selected gene in a patient cohort. We used a public database to search for genes associated with early pancreatic cancer recurrence. As a validation cohort, 201 patients who underwent radical resection in our institution were enrolled. Expression of the target gene was evaluated using immunohistochemistry (IHC). We evaluated growth and invasiveness using small interfering RNAs, then performed pathway analysis using gene set enrichment analysis. We extracted ARHGEF2 from GSE21501 as a gene with a high hazard ratio (HR) for early recurrence within 1 year. The high ARHGEF2 expression group had significantly poorer recurrence-free survival (RFS) and poorer overall survival (OS) than the low ARHGEF2 expression group. Multivariate analysis demonstrated that high ARHGEF2 expression was an independent poor prognostic factor for RFS (HR 1.92) and OS (HR 1.63). In vitro, ARHGEF2 suppression resulted in reduced cell growth and invasiveness. Bioinformatic analysis revealed that ARHGEF2 expression was associated with MYC, G2M, E2F, and CDC25A expression, suggesting that c-Myc and cell cycle genes are associated with high ARHGEF2 expression. IHC revealed a positive correlation between ARHGEF2 and c-Myc expression. High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer. |
| Databáze: | OpenAIRE |
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