Erschienen in:
03.01.2021 | Translational Research
High ARHGEF2 (GEF-H1) Expression is Associated with Poor Prognosis Via Cell Cycle Regulation in Patients with Pancreatic Cancer
verfasst von:
Yosuke Nakao, MD, Shigeki Nakagawa, MD, PhD, Yo-ichi Yamashita, MD, PhD, FACS, Naoki Umezaki, MD, PhD, Yuya Okamoto, BM, Yoko Ogata, BS, Noriko Yasuda-Yoshihara, PhD, Rumi Itoyama, MD, Toshihiko Yusa, MD, Kohei Yamashita, MD, PhD, Tatsunori Miyata, MD, PhD, Hirohisa Okabe, MD, PhD, Hiromitsu Hayashi, MD, PhD, FACS, Katsunori Imai, MD, PhD, FACS, Hideo Baba, MD, PhD, FACS
Erschienen in:
Annals of Surgical Oncology
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Ausgabe 8/2021
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Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer.