Expression of CD44 variant 9 induces chemoresistance of gastric cancer by controlling intracellular reactive oxygen spices accumulation

Background CD44 variant 9 (CD44v9) has been reported to suppress reactive oxygen spices (ROS) in association with antioxidant factors such as glutathione (GSH) and glutathione peroxidase 2 (GPx2), resulting in promoted tumor growth. Methods CD44v9 and GPx2 expression were investigated by immunohisto...

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Published in:Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2021-09, Vol.24 (5), p.1089-1099
Main Authors: Jogo, Tomoko, Oki, Eiji, Nakanishi, Ryota, Ando, Koji, Nakashima, Yuichiro, Kimura, Yasue, Saeki, Hiroshi, Oda, Yoshinao, Maehara, Yoshihiko, Mori, Masaki
Format: Article
Language:English
Subjects:
5-Fluorouracil
Abdominal Surgery
Antioxidants
Biomarkers, Tumor - genetics
Biopsy
Cancer Research
CD44 antigen
Chemoresistance
Chemotherapy
Drug Resistance, Neoplasm
Gastric cancer
Gastroenterology
Glutathione peroxidase
Humans
Hyaluronan Receptors - genetics
Immunohistochemistry
Intracellular
Medical prognosis
Medicine
Medicine & Public Health
Metastases
Multivariate analysis
Oncology
Original Article
Oxygen
Prognosis
Reactive oxygen species
Spices
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Surgical Oncology
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Summary:Background CD44 variant 9 (CD44v9) has been reported to suppress reactive oxygen spices (ROS) in association with antioxidant factors such as glutathione (GSH) and glutathione peroxidase 2 (GPx2), resulting in promoted tumor growth. Methods CD44v9 and GPx2 expression were investigated by immunohistochemistry in resected specimens from 193 gastric cancer (GC) patients without preoperative chemotherapy and in pretreatment biopsy specimens from 29 GC patients with preoperative chemotherapy. We analyzed the relationship between CD44v9 expression and clinicopathological factors, prognosis, and pathological response to chemotherapy. In GC cell lines, we examined the relationship between CD44v9 expression and chemotherapeutic sensitivity. Results In patients without preoperative chemotherapy, CD44v9 expression was significantly associated with depth of invasion, lymphatic permeation, vascular invasion, distant metastasis and GPx2 expression. In multivariate analysis, CD44v9 expression was an independent poor prognosis factor for overall survival and recurrence-free survival. In patients with preoperative chemotherapy, CD44v9 expression was significantly associated with worse pathological response and GPx2 expression. In GC cell lines, downregulation of CD44v9 expression enhanced chemotherapeutic sensitivity to 5-fluorouracil with changing GSH and ROS levels. Conclusions CD44v9-positive expression was associated with chemotherapeutic resistance by controlling intracellular accumulated ROS, suggesting that CD44v9 may be a predictive biomarker for chemotherapy in GC.
ISSN:1436-3291
1436-3305
DOI:10.1007/s10120-021-01194-5