Journal
JOURNAL OF GASTROINTESTINAL SURGERY
Volume 25, Issue 5, Pages 1147-1155Publisher
SPRINGER
DOI: 10.1007/s11605-020-04616-4
Keywords
Gastric cancer; CD44; Phosphorylated MEK; Prognosis
Categories
Funding
- National Natural Science Foundation of China [81871899]
- Construction Project of Fujian Province Minimally Invasive Medical Center, China [[2017]171]
- Science Foundation of the Fujian Province, China [2018 J01307]
- Startup Fund for Scientific Research, Fujian Medical University, China [2016QH024]
- National Institutes of Health [P30 CA008748]
- DeGregorio Family Foundation
Ask authors/readers for more resources
The study demonstrated that high CD44 and high p-MEK expression are independent negative prognostic factors for gastric adenocarcinoma patients. Targeting the RTK-RAS pathway may improve the prognosis of these patients by inhibiting metastasis and reversing chemotherapy resistance.
Purpose We have shown that activation of the receptor tyrosine kinase (RTK)-RAS pathway in gastric adenocarcinoma (GA) promotes acquisition of cancer stem-like cell (CSC) phenotypes including metastasis and chemotherapy resistance. Here, we evaluated the prognostic value of the CSC marker CD44 and the RTK-RAS activation marker phosphorylated MEK (p-MEK) in patients with resectable GA. Methods CD44 and p-MEK were measured in tumors from GA patients who underwent curative-intent gastrectomy at Fujian Medical University Union Hospital (FMUUH, n = 134) and Memorial Sloan Kettering Cancer Center (MSKCC, n = 56). Overall survival (OS) was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling. Results Despite multiple significant differences in clinicopathologic characteristics between the FMUUH and MSKCC cohorts, high CD44 and high p-MEK expression were both independent negative prognostic factors for OS on univariate analysis in both cohorts (p < 0.05). Both factors were also significant on multivariate analysis when the cohorts were combined (p <= 0.003). On subgroup analysis, the 5-year OS of patients with both high CD44 and high p-MEK was 39.5-41.6% compared with 55.4-66.4% for patients with low CD44. High CD44 expression was associated with more advanced TNM stage in the FMUUH cohort and larger tumor size and undifferentiated histology in the MSKCC cohort. High p-MEK was associated with undifferentiated histology in the FMUUH cohort and larger tumor size in the MSKCC cohort. Conclusions Increased CD44 and p-MEK expression are predictive of worse OS in GA patients. Thus, targeting the RTK-RAS pathway may benefit patients with CD44-positive, RAS-activated GA by inhibiting metastasis and reversing chemotherapy resistance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available