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.

中文翻译：

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CD44变体9的表达通过控制细胞内活性氧香料的积累诱导胃癌的化学抗性

背景

据报道，CD44 变体 9 (CD44v9) 可抑制与抗氧化因子如谷胱甘肽 (GSH) 和谷胱甘肽过氧化物酶 2 (GPx2) 相关的活性氧香料 (ROS)，从而促进肿瘤生长。

方法

CD44v9 和 GPx2 表达在来自 193 名未进行术前化疗的胃癌 (GC) 患者的切除标本和来自 29 名接受术前化疗的胃癌患者的治疗前活检标本中进行了研究。我们分析了CD44v9表达与临床病理因素、预后和对化疗的病理反应之间的关系。在 GC 细胞系中，我们检查了 CD44v9 表达与化疗敏感性之间的关系。

结果

在未进行术前化疗的患者中，CD44v9的表达与浸润深度、淋巴渗透、血管浸润、远处转移和GPx2表达显着相关。在多变量分析中，CD44v9 表达是总生存期和无复发生存期的独立不良预后因素。在术前化疗患者中，CD44v9 表达与较差的病理反应和 GPx2 表达显着相关。在 GC 细胞系中，随着 GSH 和 ROS 水平的变化，CD44v9 表达的下调增强了对 5-氟尿嘧啶的化疗敏感性。

结论

CD44v9 阳性表达通过控制细胞内累积的 ROS 与化疗耐药相关，表明 CD44v9 可能是 GC 化疗的预测生物标志物。