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Updated: Apr 8, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Activated Pak4 expression correlates with poor prognosis in human gastric cancer patients
1Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, China.
Abstract:
Despite considerable advances in gastrectomy and chemotherapy, the prognosis of gastric cancer (GC) has not noticeably improved due to lymph node or distant metastases. P21-activated serine/threonine kinase 4 (Pak4) plays an important role in cell morphology and cytoskeletal reorganization-both prerequisite steps for cell migration. However, it is still unclear if activated Pak4 (p-Pak4) is related to prognosis in GC patients. In our study, the level of p-Pak4 in 95 GC tissue specimens was examined by immunohistochemistry (IHC). We observed significant correlation between the level of p-Pak4 and grosstype (advanced stage GC vs. early stage GC, P = 0.04). Moreover, GC patients with higher p-Pak4 levels had a poorer prognosis than those with lower p-Pak4 levels (17 vs. 38 months, P = 0.001). Multivariate analysis showed that high phosphorylation level of Pak4, advanced stage GC, and lymph node metastasis were independent prognostic factors for GC patients (p-Pak4, P = 0.026; advanced stage GC, P = 0.030; lymph node metastasis, P = 0.016). In addition, in vitro assays indicated that knockdown of Pak4 accompanied with decreased p-Pak4, inhibited cell migration via downregulation of the traditional downstream signaling pathways of Pak4, LIMK1, and cofilin. In conclusion, this report reveals that high level of p-Pak4 correlates with poor prognosis in GC, thereby suggesting that p-Pak4 might be a potential prognostic marker for GC.
Insights
High levels of phosphorylated P21-activated kinase 4 (p-Pak4) correlate with poor prognosis in gastric cancer (GC) patients. This suggests p-Pak4 may serve as a valuable prognostic marker for GC, aiding in patient outcome prediction.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Gastric cancer (GC) prognosis remains poor despite advances in treatment, largely due to metastasis.
- P21-activated serine/threonine kinase 4 (Pak4) is implicated in cell migration, a key process in metastasis.
- The prognostic significance of activated Pak4 (p-Pak4) in GC is not well understood.
Purpose of the Study:
- To investigate the correlation between p-Pak4 levels and prognosis in gastric cancer patients.
- To determine if p-Pak4 is an independent prognostic factor in GC.
- To explore the role of Pak4 in GC cell migration in vitro.
Main Methods:
- Immunohistochemistry (IHC) was used to quantify p-Pak4 levels in 95 GC tissue specimens.
- Statistical analyses, including multivariate analysis, were performed to assess prognostic significance.
- In vitro cell migration assays were conducted following Pak4 knockdown.
Main Results:
- Higher p-Pak4 levels significantly correlated with advanced stage GC.
- GC patients with high p-Pak4 levels exhibited significantly poorer prognosis (17 months vs. 38 months).
- High p-Pak4, advanced stage, and lymph node metastasis were identified as independent prognostic factors.
- Pak4 knockdown inhibited GC cell migration by downregulating LIMK1 and cofilin pathways.
Conclusions:
- Elevated p-Pak4 levels are associated with poor prognosis and advanced disease in gastric cancer.
- p-Pak4 represents a potential novel prognostic biomarker for gastric cancer.
- Targeting Pak4 signaling may offer therapeutic strategies for inhibiting GC cell migration.
